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Biomedical subjects

C C Hsieh

Publications and source records attributed to C C Hsieh.

At least 73 records · Page 4Linked to original sources
PubMed1999

Hormonal, lifestyle, and dietary factors in relation to leptin among elderly men.

BACKGROUND: Leptin, the adipocyte-secreted protein product of the ob gene, has been strongly linked to obesity and is believed to play a role in the regulation of the reproductive system. This study examines the potential influence of lifestyle and dietary factors, as well as of other hormones, on serum levels of leptin. METHODS: The authors studied a population of 48 healthy elderly Greek men. Sera from these men were analyzed for leptin, several steroid hormones, sex hormone-binding globulin, and insulin-like growth factor 1. The authors also utilized data from food frequency questionnaires and information on demographic, anthropometric, and lifestyle (cigarette smoking, alcohol and coffee drinking) factors. RESULTS: Using linear regression modeling, serum leptin levels were inversely associated with testosterone and positively associated with estradiol and dehydroepiandrosterone sulfate, after adjustment for the other hormones and body mass index (BMI). Leptin levels in men with a BMI >30 kg/m2 were 170% higher than in men with a BMI <27 kg/m2 (95% CI 63- 346%). Height was also positively associated with leptin, independent of BMI. No notable relationships were observed between leptin, on the one hand, and smoking, alcohol drinking, coffee drinking, or total energy intake, on the other. When total energy intake was separated into its three major components (carbohydrate, fat, and protein), it appeared that fat intake may have an isocalorically differential effect on serum leptin levels; one marginal quintile increase in fat intake corresponded to an 11% increase in leptin (95% CI 0-24%). CONCLUSION: Serum levels of leptin may be influenced by other endocrine factors, especially testosterone and estradiol, and may be positively associated with excess fat intake independently of obesity.

Aged↗
PubMed1999

Effects of butyrate and propionate on the adhesion, growth, cell cycle kinetics, and protein synthesis of cultured human gingival fibroblasts.

BACKGROUND: Various periodontal and root canal pathogens, such as the Bacteroides species, can produce significant amounts of short chain fatty acids (SCFA). The roles of SCFA in the pathogenesis of periodontal disease are still not fully understood. METHODS: We therefore investigated 2 main SCFA, butyrate and propionate, on the functional behavior of cultured human gingival fibroblasts (GF) such as cell growth, protein synthesis, cell adhesion capacity, and cell cycle progression. RESULTS: Butyrate and propionate inhibited the growth of healthy (HGF) and inflamed gingival fibroblasts (IGF) in a dose dependent manner. At concentrations of 4, 8, and 16 mM, butyrate suppressed the cell growth by 11 to 58%, 16 to 60%, and 50 to 71%, respectively. The response of cultured gingival fibroblasts to SCFA showed individual differences. Morphologically, GF became larger and more flattened in appearance following exposure to butyrate (>8 mM) and propionate (>24 mM) for 5 days. Inhibitory effects of butyrate (>2 mM) and propionate (>8 mM) on the growth of GF were due possibly to their inhibition of cell-cycle progression. At concentrations of 2 and 8 mM, butyrate led to G0/G1 arrest. Elevation of the exposure concentration to 8 to 24 mM further result in G2/M phase arrest of GF. On the other hand, propionate, at concentrations ranging from 4 to 24 mM, led to G0/G1 arrest. Butyrate (>2 mM) inhibited the proline-rich protein synthesis of GF. At concentrations of 4, 8, 16, and 24 mM, butyrate inhibited the protein synthesis of HGF-1 by 42%, 43%, 51%, and 54%, respectively. In all strains of cultured GF, the suppressive effect of propionate is less than that of butyrate. At concentration range of 4 to 24 mM, propionate suppressed the protein synthesis of HGF-1 by 23 to 43%. However, both butyrate and propionate (4 to 48 mM) exerted little effects on the adhesion of GF to type I collagen within 3 hours of incubation. CONCLUSIONS: These results suggested that SCFA released by pathogenic microorganisms can contribute to the gingival tissue dysfunction and breakdown through their actions on specific biological functions of GF.

Butyrates↗
PubMed1999

Leiomyosarcoma of the gastric cardia and fundus.

BACKGROUND: Gastric leiomyosarcoma is rare among gastric malignancies, and only 20% of the cases are located in the gastric cardia or fundus. It has clinical manifestations different from tumors in other sites of the stomach. We reviewed cases of leiomyosarcoma of the gastric cardia or fundus to evaluate their clinicopathologic characters and patient survival. METHODS: From May, 1981, to June, 1998, a total of 15 patients who underwent curative resection of leiomyosarcoma of the gastric cardia or fundus were retrospectively identified and studied. All the clinical and pathologic data were reviewed and recorded. RESULTS: There were 11 men and four women. Their mean age was 59.1 years (range, 37-73 years). Tarry stools and epigastric fullness and pain were the most common symptoms, followed by body weight loss. All 15 patients had submucosal tumors in the gastric cardia or fundus, as shown by endoscopy, barium contrast radiography and computerized tomography. The incidence of esophageal involvement by the tumors was quite low. The mean tumor size was 10 cm, ranging from 4 cm to 20 cm. Locoregional organs were involved in nine patients. The median and mean survivals were 17.8 months and 31.7 months, respectively (range, 10.1-80.1 months) after curative resection. The three-year and five-year survival rates were 53% and 22%, respectively. CONCLUSIONS: The definitive preoperative diagnosis of the tumor is difficult before surgery, even though imaging studies show positive findings. Surgical resection with an adequate safe margin of normal tissue is the treatment of choice. Tumor size, serosal invasion with locoregional organ involvement and high tumor grade were the prognostic factors in the study.

Adult↗
PubMed1998

Parity, age at first birth and the risk of carcinoma in situ of the breast.

Epidemiological studies of in situ breast cancer are sparse, and the role of reproductive history, an established risk modifier for invasive breast cancer, remains incompletely investigated. To examine possible associations with parity and age at first birth, we undertook a case-control study nested in a nationwide cohort of Swedish women. The reproductive history of 1,368 women aged 65 or younger with a diagnosis of carcinoma in situ of the breast were compared with that of 6,837 age-matched controls drawn randomly from a population-based Fertility Registry. Statistical analyses were performed by conditional logistic regression. Compared to nulliparous women, ever-parous women were at a reduced risk of carcinoma in situ of the breast. The risk decreased with number of live births, with the estimated risk reduction in the highest parity group (5+), being of the same magnitude as that reported for invasive breast cancer. By contrast, a positive association with increasing age at first birth was somewhat less pronounced than that observed previously in the same data set with respect to invasive breast cancer. Our findings indicate that parity affects the risk of invasive breast cancer and carcinoma in situ similarly, whereas the effect of age at first birth appears to be weaker for the risk of carcinoma in situ.

Adult↗
PubMed1998

The fluctuating phenotype of the lymphohematopoietic stem cell with cell cycle transit.

The most primitive engrafting hematopoietic stem cell has been assumed to have a fixed phenotype, with changes in engraftment and renewal potential occurring in a stepwise irreversible fashion linked with differentiation. Recent work shows that in vitro cytokine stimulation of murine marrow cells induces cell cycle transit of primitive stem cells, taking 40 h for progression from G0 to mitosis and 12 h for subsequent doublings. At 48 h of culture, progenitors are expanded, but stem cell engraftment is markedly diminished. We have investigated whether this effect on engraftment was an irreversible step or a reversible plastic feature correlated with cell cycle progression. Long-term engraftment (2 and 6 mo) of male BALB/c marrow cells exposed in vitro to interleukin (IL)-3, IL-6, IL-11, and steel factor was assessed at 2-4-h intervals of culture over 24-48 h using irradiated female hosts; the engraftment phenotype showed marked fluctuations over 2-4-h intervals, with engraftment nadirs occurring in late S and early G2. These data show that early stem cell regulation is cell cycle based, and have critical implications for strategies for stem cell expansion and engraftment or gene therapy, since position in cell cycle will determine whether effective engraftment occurs in either setting.

Animals↗
PubMed1998

Parity and the risk of pancreatic cancer: a nested case-control study.

Smoking is the only generally accepted risk factor for pancreatic cancer. Reproductive history has in recent studies been associated with pancreatic cancer, but with contradictory results. In order to evaluate a possible association between age at first birth and the number of births and pancreatic cancer, we conducted a nested case-control study by linking 2 Swedish nationwide registries: the Cancer Registry and The Fertility Registry. Among women born between 1925 and 1970, 1,015 patients with pancreatic cancer were compared with 5,073 age-matched controls. No association between pancreatic cancer and number of births was found. Age at first birth was inversely related with the risk of pancreatic cancer (OR per 5 years = 0.90; 95% CI 0.83-0.97; p = 0.01), an association mainly confined to women with a diagnosis of pancreatic cancer before 50 years of age (OR per 5 years = 0.85; 95% CI 0.73-1.00; p = 0.04). This trend remained after adjustment for parity, but was less prominent. Young age at first birth and high parity in Sweden are, however, associated with an increased frequency of smoking, thus at least some of the increased risk for pancreatic cancer in women with young age at first birth is likely to be explained by smoking acting as a confounder.

Adolescent↗
PubMed1998

Regulation of LPS-mediated induction of C/EBP delta gene expression in livers of young and aged mice.

The C/EBP family of transcription factors plays a major role in the regulation of families of stress response genes, in particular, the acute phase response genes. We have examined expression of the C/EBP delta gene during the bacterial lipopolysaccharide mediated induction of the acute phase response in livers of young (4 months) and aged (24-28 months) male C57B1/6 mice by Northern, Western, and Southwestern analyses. C/EBP delta mRNA is present at a low constitutive level, is induced by lipopolysaccharide, and reaches the same induced level in young and aged mice. Aged mice, however, show a higher constitutive, uninduced mRNA pool level and a delay in recovery to uninduced levels after lipopolysaccharide treatment. C/EBP delta mRNA is observable 30 min after lipopolysaccharide in total RNA, cytoplasmic and polysomal fractions. Specific full length 28-kDa nascent peptides are detectable in polysomes 90 min after lipopolysaccharide. mRNA and nascent peptides cosediment with large polysomes and C/EBP delta mRNA is shifted to larger polysomes in lipopolysaccharide treated aged mice, consistent with an increased rate of initiation. Specific DNA-binding activity of C/EBP delta protein in nuclear extracts was examined by electromobility shift and antibody supershift assay. The levels of C/EBP delta binding-activity, are consistent with the changes in mRNA levels in young lipopolysaccharide treated livers. These studies support our hypothesis that aged mice exhibit a state of chronic inflammation or stress in the absence of a stressor.

Acute-Phase Reaction↗
PubMed1998

Body mass index, cigarette smoking, and other characteristics as predictors of self-reported, physician-diagnosed gallbladder disease in male college alumni.

Despite the high prevalence of gallbladder disease in industrialized countries, little is known about the predictors of the disease, especially in men. The authors prospectively studied 16,785 alumni of Harvard University, aged 15-24 years, who were followed for up to 61 years. The health characteristics of these men were ascertained from their college entrance physical examination done in 1916-1950, and updated via mailed questionnaires in 1962 or 1966 (1962/1966). Alumni subsequently self-reported physician-diagnosed gallbladder disease on further mailed questionnaires in 1972 or 1977. Between college time and 1962/1966, 371 gallbladder disease cases occurred. An additional 314 cases occurred after 1962/1966. With respect to college characteristics, after adjustment for potential confounders, the authors found that body mass index (BMI), smoking, physical activity, blood pressure, and consumption of alcohol, coffee, or tea were unrelated to risk. However, BMI in 1962/1966 was directly related to risk of subsequent gallbladder disease, as was BMI gain since college (p, trend = 0.002 and 0.013, respectively). Compared with men with BMI < 22.0, men with BMI > or = 27.0 had a rate ratio of 2.71 (95% confidence interval (CI) 1.57-4.66) for risk of contracting the disease. Men who gained > or = 6.0 BMI units since college had a rate ratio of 1.46 (95% CI 0.86-2.46) compared with men who gained -0.9 to +0.9 BMI units. Compared with never smokers, men who smoked pipes or cigars or < 1 pack of cigarettes daily in 1962/1966 had a rate ratio of 1.43 (95% CI 1.00-2.06), while heavier cigarette smokers had a rate ratio of 1.52 (95% CI 1.03-2.24). Neither physical activity nor physician-diagnosed hypertension or diabetes mellitus in 1962/1966 predicted risk.

Adolescent↗
PubMed1998

Induction of a subgroup of acute phase protein genes in mouse liver by hyperthermia.

We have demonstrated that two members of the acute phase reactant family of positively regulated genes, alpha 1-acid glycoprotein (AGP-1 and AGP-2) and C-reactive protein (CRP) are induced by hyperthermia, while two others, the serum amyloid A (SAA) and alpha 1-antitrypsin (AT) genes, are not. Albumin (ALB), a negative acute phase reactant gene, is also induced by hyperthermia. The AGP-1, AGP-2, and CRP genes require glucocorticoids, but not IL-6, IL-1 beta or TNF alpha in response to hyperthermia. As with LPS, the C/EBP beta mRNA levels increased, while the C/EBP alpha mRNA levels decreased in response to LPS. In contrast to the LPS response, C/EBP delta was unchanged. Protein pool levels and DNA-binding activities of the 35 and 20 kDa C/EBP beta isoforms increase, whereas protein pool levels of the 42 kDa C/EBP alpha decrease and the 30kDa remained high. These studies suggest that the synthesis of specific C/EBP alpha and C/EBP beta isoforms is induced by hyperthermia, and that the regulation of the AGP-1 and AGP-2 genes during heat stress may involve one of these isoforms. The difference between the responses to hyperthermia and LPS is that the former, may not involve the participation of cytokines. Furthermore, since cis-acting heat shock elements (HSE) are located in the promoter regions of the ALB, CRP, and C/EBP beta genes, these regulatory sequences may be involved in the in vivo activation of these genes by hyperthermia.

Acute-Phase Proteins↗
PubMed1998

Migration of vascular smooth muscle cells is enhanced in cultures derived from spontaneously hypertensive rat.

Migration of vascular smooth muscle cells (SMC) constitutes a common step in neointimal formation which occurs in several vascular diseases. Whether the migratory response of SMC derived from hypertensive animals is different to that of controls may provide a clue to the link between hypertension and atherosclerosis. We examined the migratory responses of SMC from cell cultures and ring explants (thin aortic ring segment) and compared these responses between normotensive and hypertensive rats at two different ages. Both scrape-wound assay and transwell chambers from cultured aortic SMC as well as aortic ring explant cell outgrowth models were employed. The aortae were obtained from male spontaneously hypertensive rats (SHR) and their normotensive counterpart the Wistar-Kyoto rat (WKY) at 5 and 20 weeks of age. Migration was induced by fetal bovine serum or platelet-derived growth factor (PDGF) and migrated cells were counted at different times following stimulation. We found that SMC migration exhibited a high sensitivity to serum (range of ED50: 2.2-3.6%), migration of SMC from 20-week-old SHR exceeded (by 46%, P<0.025) that of SMC from age-matched WKY and the difference became significant as early as 8 h after stimulation by serum. Chemotaxis induced by PDGF (2 h) exhibited similar differences. An elevated migratory response in SHR-SMC was also found in cells derived from 5-week-old rats in whom the blood pressure was normal. In younger animals, cell outgrowth from SHR aortic ring explants also accumulated more cells compared with WKY without a higher growth rate, thus suggesting that SHR-SMC have a higher migratory response ex vivo. In conclusion, aortic SMC migration appeared to be enhanced in various preparations from SHR. This difference also existed in young animals before the elevation of blood pressure occurred and might contribute partly to the role of hypertension as a risk factor for atherosclerosis.

Aging↗
PubMed1998

Prognostic significance of HER-2/neu overexpression in stage I adenocarcinoma of lung.

BACKGROUND: Even with early diagnosis and adequate resection, the 5-year survival rate for stage I lung cancer patients is around 60% to 70%. Overexpression of HER-2/neu protein is associated with poor prognosis in lung cancers. In this study, we evaluated the expression of HER-2/neu in cancer cells of lung and assessed their clinicopathologic and prognostic significance. METHODS: From 1986 to 1995, clinical data on 42 consecutive patients who underwent complete surgical resection for stage I lung adenocarcinoma were collected. Expression of HER-2/neu in paraffin-embedded tumor samples was determined by immunohistochemistry and scored with a semiquantitative method. RESULTS: Twenty-one of 42 patients were positive for HER-2/neu overexpression in tumor. Compared with patients with low HER-2/neu expression, patients with HER-2/neu overexpression had a significantly higher incidence of early tumor recurrence (p = 0.014). Survival was also significantly better in patients without HER-2/neu overexpression than in those with HER-2/neu overexpression (p = 0.0047). By univariate analysis, HER-2/neu overexpression and poor cell differentiation are two important factors correlated with poor prognosis. CONCLUSIONS: Expression of HER-2/neu oncoprotein in stage I lung adenocarcinoma can predict the tumor's aggressiveness. Early tumor recurrence was frequently detected in patients with HER-2/neu overexpression. We recommend an individualized therapeutic strategy based on the level of HER-2/neu oncoprotein in the tumor cells.

Adenocarcinoma↗
PubMed1998

Ameliorating effect of p-hydroxybenzyl alcohol on cycloheximide-induced impairment of passive avoidance response in rats: interactions with compounds acting at 5-HT1A and 5-HT2 receptors.

The effect of p-hydroxybenzyl alcohol (HBA) on cycloheximide (CXM)-induced impairment in the step-through passive avoidance task was investigated in rats and compared to the effect of the nootropic piracetam. HBA and piracetam significantly counteracted the CXM-induced shortening of retention latencies. The effect of HBA was a bell-shaped dose-response curve with a maximal effect of 5 mg/kg. The counteractive effect of HBA was not depressed by either scopolamine or mecamylamine. The serotonin (5-HT) releaser, p-chloroamphetamine, and presursor, 5-hydroxytryptophan, significantly antagonized the counteractive effect of HBA on the CXM-induced shortening of retention latencies. Furthermore, the counteractive effect was also inhibited by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane [(+/-)-DOI], but potentiated by the 5-HT1 receptor antagonist (+/-)-pindolol and the 5-HT2 receptor antagonist ritanserin. There results suggest that the beneficial effect of HBA on CXM-induced impairment is amplified by treatment with serotonergic receptor antagonists but reduced by serotonergic 5-HT1A and 5-HT2 receptor agonists, and insensitive to cholinergic manipulations.

Animals↗
PubMed1998

Thrombin-induced DNA synthesis of cultured human dental pulp cells is dependent on its proteolytic activity and modulated by prostaglandin E2.

To clarify the roles of alpha-thrombin and prostaglandin E2 (PGE2) in the healing and inflammatory processes of dental pulp, their effects on the DNA synthesis of human pulp cells were investigated by measurement of [3H]thymidine incorporation. At a concentration range of 1 to 25 units/ml, alpha-thrombin stimulated DNA synthesis of the pulp cells by 1.5 to 2.6-fold. On the contrary, PGE2 (> 0.05 microgram/ml) suppressed DNA synthesis by 24 to 39%. Using reverse transcriptase-polymerase chain reaction, thrombin receptor mRNA expression was identified in the pulp cells. Furthermore, alpha-thrombin-induced DNA synthesis could be inhibited by antithrombin III (2 units/ml) with heparin (2 units/ml) or D-Phe-Pro-ArgCH2Cl (50 micrograms/ml). PGE2 (0.1 to 0.5 microgram/ml) also inhibited the thrombin-induced DNA synthesis by 39 to 64%. These results imply that pulp cells express the thrombin receptor that is activated by the serine protease activity of thrombin. Interactions of thrombin and PGE2 are important in modulating the inflammatory and healing processes of the pulp.

Cells, Cultured↗
PubMed1998

Prevalence and distribution of cervical dentin hypersensitivity in a population in Taipei, Taiwan.

The prevalence, distribution, and possible causal factors of cervical dentin hypersensitivity were studied in a population attending the Health Examination Center of National Taiwan University Hospital. A total of 780 patients were examined for the presence of cervical dentin hypersensitivity by means of a questionnaire and intraoral tests. There were 253 patients (32%) who claimed to have hypersensitive teeth at present and 90 patients (12%) who reported a history of hypersensitive teeth. The intraoral distribution of hypersensitivity showed that premolars and molars were the most common teeth sensitive to the air and probe stimuli, while the incisors were the least sensitive ones. The presence and history of dentin hypersensitivity were positively correlated with previous tooth-brushing and periodontal disease. Only a few of the patients who claimed to have dentin hypersensitivity had tried treatment with desensitizing tooth-pastes (11%) or sought professional help (5%).

Adult↗
PubMed1998

Differential expression of interleukin-1 beta and interleukin-6 in human fetal serum and meconium-stained amniotic fluid.

The study was designed to investigate the expression of the inflammatory cytokines interleukin-1 beta and interleukin-6 in meconium-stained amniotic fluid and in fetal cord serum. Amniotic fluid and fetal cord serum specimens were collected from 10 and 9 women with meconium-stained and clear amniotic fluid, respectively, during Caesarean operation at labor The mean concentrations of interleukin-1 beta found in clear and meconium-stained amniotic fluid were 10.0 and 54.5 pg/ml, respectively, and the difference was not statistically significant. On the other hand, the concentrations of interleukin-6 in meconium-stained amniotic fluid (774 pg/ml) was significantly higher than that found in clear amniotic fluid (149 pg/ml) (P = 0.0036). The differences of levels of both interleukin-1 beta and interleukin-6 in fetal cord serum specimens were not significant between neonates born to mothers with either clear or meconium-stained amniotic fluid (P = 0.8702 and 0.2987, respectively). The results of this study suggest that the production of at least one of the inflammatory cytokines, interleukin-6, is associated with the meconium found in amniotic fluid.

Amniotic Fluid↗
PubMed1998

Predictors of sex hormone levels among the elderly: a study in Greece.

This study examines the relationship between a series of epidemiologic parameters (age, height, body mass index (BMI), smoking, alcohol consumption, and coffee drinking) and serum concentrations of testosterone, estradiol, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS). Among 52 healthy, elderly Greek men, we observed that serum levels of DHEAS decreased with increasing age [19% decline per 5-year increase in age, 95% CI, -2.1-(-33.5)], obesity [48% decline for BMI >30 kg/m2 compared to <27 kg/m2, CI, -15.7-(-68.7)], and current smoking [37% decline compared to nonsmokers, CI, -9.5-(-57.2)]. Estradiol concentrations increased with increasing BMI [77.1% increase for BMI >30 kg/m2 compared to <27 kg/m2, CI, -12.0-256.3], alcohol drinking [66% increase for > or = 7 glasses/week compared to <7 glasses/week, CI, 4.4-164.4], and coffee drinking [59% increase for > or = 14 cups/week compared to > or = 14 cups/ week, CI, -0.5-155.9], and decreased among current smokers [40% decline compared to nonsmokers, CI, -64.9-0.8]. SHBG was marginally positively associated with increasing age [13% increase per 5 years, CI, -0.5-29.6]. Testosterone was significantly related only to current smoking [27% decline compared to nonsmokers, CI, -45.4-(-3.1)]. These findings suggest that several variables appear to be associated with sex steroid levels and the influence of these findings on the occurrence of hormone-related conditions warrants further exploration.

Age Factors↗
PubMed1998

Cytotoxicity of sodium fluoride on human oral mucosal fibroblasts and its mechanisms.

Because sodium fluoride (NaF) is widely used for prevention of dental caries, pathobiological effects of NaF were investigated on human oral mucosal fibroblasts. The results showed that NaF was cytotoxic to oral mucosal fibroblasts at concentrations of 4 mmol/L or higher. Exposure of cells to NaF for 2 h also inhibited protein synthesis, cellular ATP level and functional mitochondrial activities in a dose-dependent manner. However, incubation of cells with NaF up to 12 mmol/L for 2 h depleted only 13% of cellular glutathione level. The IC50 of NaF on cellular ATP level was about 5.75 mmol/L. Preincubation of the cells with pyruvate and succinate did not protect cells from NaF-induced ATP depletion. At concentrations of 4 mmol/L, 8 mmol/L and 12 mmol/L, NaF inhibited 31%, 56% and 57% of mitochondrial functions, respectively, after 2 h incubation. No significant inhibition for NaF was found at concentrations lower than 2 mmol/L (40 ppm). These results indicate that NaF can be toxic to oral mucosal fibroblasts in vitro by its inhibition of protein synthesis, mitochondrial function and depletion of cellular ATP. Because of repeated and long-term usage of NaF, more detailed studies should be undertaken to understand its toxic effects in vitro and in vivo.

Adenosine Triphosphate↗