Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “EXERTION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,603 records · Page 89Linked to original sources
PubMedDate not supplied

Bovine seminal ribonuclease exerts selective cytotoxicity toward neuroblastoma cells both sensitive and resistant to chemotherapeutic drugs.

BACKGROUND: Bovine seminal ribonuclease (BS-RNase) exerts selective cytotoxicity toward different types of tumor cells. In the present study, we tested the effects of BS-RNase on cultured neuroblastoma (NB) cells resistant to chemotherapeutic agents. The selectivity of the antitumoral activity of BS-RNase was evaluated using cultures of CD34+ hematopoietic stem cells. MATERIALS AND METHODS: Human NB cell lines including IMR-32, UKF-NB-2 and UKF-NB-3 were selected for resistance against vincristine, doxorubicin or cisplatin by exposure to increasing concentrations of the respective drug. The cytotoxicity of the drugs to NB cells was evaluated using a clonogenic assay in a methylcellulose medium. Peripheral blood progenitor cells were obtained from adult healthy donors by positive selection using specific anti-CD34+ antibodies. The toxicity of BS-RNase to CD34+ cells was assessed in the direct clonogenic assay using methylcellulose medium or in ex vivo expansion culture supplemented with hematopoietic growth factors. RESULTS: In the clonogenic assay it was shown that BS-RNase completely inhibits growth of both parental NB cells and their sublines resistant to chemotherapeutic drugs at concentrations (up to 50 micrograms/ml) which have no significant influence on the growth of colony-forming units, granulocyte macrophage and erythroid burst-forming units. Moreover, BS-RNase had no effect on the ex vivo expansion of total hematopoietic cells or of colony-forming cells from CD34+ progenitors. CONCLUSIONS: BS-RNase is a highly efficient agent against NB cells resistant to chemotherapeutic drugs. The lack of toxicity to hematopoietic progenitor cells suggests that BS-RNase is also likely to have tolerable hematopoietic toxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis.

Arsenic trioxide (As(2)O(3)) has recently been used successfully in the treatment of acute promyelocytic leukemia and has been shown to induce partial differentiation and apoptosis of leukemic cells in vitro. However, the mechanism by which As(2)O(3) exerts its antileukemic effect remains uncertain. Emerging data suggest that the endothelium and angiogenesis play a seminal role in the proliferation of liquid tumors, such as leukemia. We have shown that activated endothelial cells release cytokines that may stimulate leukemic cell growth. Leukemic cells, in turn, can release endothelial growth factors, such as vascular endothelial growth factor (VEGF). On the basis of these observations, we hypothesized that As(2)O(3) may interrupt a reciprocal loop between leukemic cells and the endothelium by direct action on both cell types. We have shown that treatment of proliferating layers of human umbilical vein endothelial cells (HUVECs) with a variety of concentrations of As(2)O(3) results in a reproducible dose- and time-dependent sequence of events marked by change to an activated morphology, up-regulation of endothelial cell adhesion markers, and apoptosis. Also, treatment with As(2)O(3) caused inhibition of VEGF production in the leukemic cell line HEL. Finally, incubation of HUVECs with As(2)O(3) prevented capillary tubule and branch formation in an in vitro endothelial cell-differentiation assay. In conclusion, we believe that As(2)O(3 )interrupts a reciprocal stimulatory loop between leukemic cells and endothelial cells by causing apoptosis of both cell types and by inhibiting leukemic cell VEGF production. (Blood. 2000;96:1525-1530)

Antineoplastic Agents↗
PubMed2000

A simple method for measuring the relative force exerted by myosin on actin filaments in the in vitro motility assay: evidence that tropomyosin and troponin increase force in single thin filaments.

We have studied the effect of an internal load on the movement of actin filaments over a bed of heavy meromyosin (HMM) in the in vitro motility assay. Immobilized alpha-actinin can bind to actin filaments reversibly and ultimately stop the filaments from moving. Above a critical concentration of alpha-actinin, thin filament velocity rapidly diminished to zero. The fraction of thin motile filaments decreased linearly to zero with increasing alpha-actinin concentration. The concentration of alpha-actinin needed to stop all filaments from moving (0.8 microg/ml with actin) was very consistent both within and between experiments. In the present study we have defined the 'index of retardation' as the concentration of alpha-actinin needed to stop all filament movement, and we propose that this index is a measure of the isometric force exerted by HMM on actin filaments. When we measured the effect of immobilized alpha-actinin on motility in the presence of 10 mM P(i) we found that the index of retardation was 0.62+/-0.07 (n=3) times that in the absence of P(i). This observation is in agreement with the reduction of isometric tension in chemically-skinned muscle due to P(i). In a series of comparative experiments we observed that tropomyosin and troponin increase the index of retardation and that the degree of increase depends upon the tropomyosin isoform studied. The index of retardation of actin is increased 1.8-fold by skeletal-muscle tropomyosin, and 3-fold by both cardiac-muscle and smooth-muscle tropomyosin. In the presence of troponin the index of retardation is 2.9-3.4-fold greater than that of actin with all tropomyosin isoforms.

Actins↗
PubMed2000

IFN-alpha and IL-18 exert opposite regulatory effects on the IL-12 receptor expression and IL-12-induced IFN-gamma production in mouse macrophages: novel pathways in the regulation of the inflammatory response of macrophages.

We characterized the IL-12 response of mouse macrophages in terms of modulation of IFN-gamma production by cytokines (IFN-alpha and IL-18) and regulation of IL-12 receptor expression. Beta1 and beta2 IL-12R chain mRNA expression increased with time in culture in the absence of exogenous stimulation, with concomitant acquisition of responsiveness to IL-12 for IFN-gamma production. Expression of the IL-12R beta1 chain mRNA was increased further following IL-12 treatment as a consequence of IFN-gamma expression. IL-12 response was regulated differentially by IFN-alpha and IL-18. Neutralization of endogenous type I IFN increased IFN-gamma secretion, whereas exogenous IFN-alpha reduced it. In contrast, IL-18 enhanced IFN-gamma mRNA accumulation and IFN-gamma secretion in IL-12-stimulated, but not -untreated, cultures. The opposite effects exerted by IFN-alpha and IL-18 mirror their mutual capacity of regulating-in a negative or positive manner, respectively-the expression of the IL-12R beta1 chain. We suggest that differential regulation of IL-12 response by IFN-alpha and IL-18 can represent previously unrecognized regulatory mechanisms for maintaining suitable levels of differentiation/activation in macrophages.

Animals↗
PubMed1975

[Physical exertion tests in patients with acute myocardial infarct at the hospital stage of rehabilitation].

The aim of the work is to clarify the part of physical exertion tests applied to patients early after myocardial infarction, i.e. on the 30--35th day of the affection and also to appraise the reserves of the coronary circulation with a definite threshold tolerance to physical efforts. Tests with a graded physical loading were set up in 50 patients with acute macrofocal (including 34 transmural) myocardial infarction at the time of completion of the intrahospital rehabilitation program that included the regimen of an early activation. A continually-rising type of loading with an initial rating of 150 kgm/min was used. At the instant of effort the ECG was being registered in 4 chest leads. The threshold load-rating was found to average 315 kgm/min and the sum-total of the work performed equaled 2190 kgm. Tests with graded physical loading are of great importance for elaboration of concrete recommendations for rehabilitation and prophylactic measures in patients with acute myocardial infarction.

Adult↗
PubMed2001

Nerve growth factor exerts differential effects on the growth of human pancreatic cancer cells.

Nerve growth factor (NGF) exerts both stimulatory and inhibitory effects on neuronal and certain nonneuronal tumors with the effect based on the type of tumor. We investigated NGF and its receptors (TrkA and p75) in pancreatic cancer cells (PANC-1, MIA-PaCa-2, CAPAN-1, ASPC-1, and T3M4) by reverse transcription-PCR, Western blot analysis, NGF ELISA, and growth assays. NGF mRNA was present at comparable levels in all five pancreatic cancer cell lines. TrkA expression was relatively high in PANC-1 and MIA-PaCa-2 cells and low in CAPAN-1, ASPC-1, and T3M4 cells. p75 expression was high in PANC-1, MIA-PaCa-2, and T3M4 cells, moderate in CAPAN-1, and low in ASPC-1 cells. By ELISA assay, the intracellular NGF content in all cell lines was approximately 40 pg/10(6) cells. NGF content increased significantly in PANC-1 and MIA-PaCa-2 cells when these cells were cultured with serum-free media, whereas there was no change in the other cancer cell lines. PANC-1 and MIA-PaCa-2 cells but not the other cell lines released NGF in the culture media. Exogenous NGF stimulated the growth of PANC-1 and MIA-PaCa-2 cells, inhibited the growth of T3M4 and CAPAN-1 cells in a dose- and time-dependent manner, and did not affect the growth of ASPC-1 cells. NGF led to the phosphorylation of TrkA, mitogen-activated protein kinase (MAPK), and p38 MAPK but not stress-activated protein kinase/c-Jun NH2-terminal kinase in PANC-1 and MIA-PaCa-2 cells. In contrast, in the other pancreatic cancer cell lines none of these kinases were phosphorylated by NGF. In conclusion, the effects of NGF on pancreatic cancer cell growth are dependent on the expression levels and the balance of its TrkA and p75 receptors. NGF-induced pancreatic cancer cell growth seems to be mediated through the phosphorylation of TrkA and subsequently via MAPK. These results point to a previously unknown autocrine/paracrine pathway in pancreatic cancer, suggesting that NGF-TrkA interactions are important factors influencing cell growth and spread in this malignancy.

Blotting, Western↗
PubMed2000

[Genistein exerts multiple suppressive effects on human breast carcinoma cells].

OBJECTIVE: To study the suppressive effects of genistein on progression of breast carcinoma. METHODS: In vitro cell culture, animal studies, zymography, Northern and Western blot were used in this study. RESULTS: Genistein inhibited in vitro invasion of MCF-7 and MDA-MB-231 cells. This inhibition was associated with down-regulation of MMP-9 and up-regulation of TIMP-1. These effects were also demonstrated in vivo. Genistein inhibited growth of the breast cancer cells transplanted in nude mice. The growth inhibitory effect was associated with increased tumor cell apoptosis, and up-regulated p21WAF1/CIP1 expression. Furthermore, genistein inhibited angiogenesis as shown by decreased vessel density and decreased production and release of VEGF and TGF-beta 1. CONCLUSION: Genistein exerts multiple suppressive effects on breast carcinoma. It may help halt its progression.

Animals↗
PubMed2002

Ratings of perceived exertion in active muscle during high-intensity and low-intensity resistance exercise.

This investigation compared ratings of perceived exertion specific to the active muscles used during resistance exercise (RPE-AM) using the 15-category Borg scale during high-intensity (HIP) and low-intensity (LIP) weight lifting. Ten men (23.2 +/- 3.6 years) and 10 women (21.8 +/- 2.7 years) performed 2 trials consisting of seven exercises: bench press (BP), leg press, latissimus dorsi pull down, triceps press, biceps curl, shoulder press, and calf raise. The HIP and LIP protocols were completed in counterbalanced order. During HIP, subjects completed 5 repetitions using 90% of 1 repetition maximum (1RM). RPE-AM was measured after every repetition. During LIP, subjects completed 15 repetitions using 30% of 1RM. RPE-AM was measured after every third repetition. RPE-AMs were greater (p <or= 0.001) for HIP than for LIP for each exercise. For example, the mean initial BP RPE was 14.11 +/- 2.08 for the HIP and 8.34 +/- 1.35 for the LIP. Performing few repetitions using heavier weight is perceived to be more difficult than lifting comparatively lighter weight with more repetitions when external work is held constant.

Adult↗
PubMed2002

Recombinant human Flt3 ligand exerts both direct and indirect effects on hematopoiesis.

OBJECTIVE: To investigate the direct effects of the Flt3 ligand (FL) on hematopoiesis, such as the stimulation of the formation of hematopoietic colonies and the proliferation of dendritic cells, as well as the indirect stimulation of hematopoiesis, especially via the proliferation of endothelial cells. METHODS: Mononuclear cells from human cord blood were plated in methylcellulose medium containing different cytokines to induce hematopoietic colony formation. Dendritic cells (DCs) were induced from the mononuclear cells with a cytokine cocktail with or without recombinant human soluble FL (rhFL; 100 ng/ml). The Flt3 receptors on the surface of a human microvascular endothelial cell line (ECV) were analyzed by flow cytometry. The proliferation of ECV stimulated by rhFL was measured with the microculture tetrazolium assay. The levels of FL, IL-6, IL-8, G-CSF and GM-CSF in the supernatant of ECV cultures were measured by enzyme linked immunoabsorbent assay (ELISA). RESULTS: rhFL stimulates colony formation from cord blood when used as a sole stimulant. FL in combination with other cytokines increased colony formation significantly. The number of DCs was approximately 2.5 times higher when rhFL was used. rhFL stimulates the proliferation of ECV on which Flt3 receptors are expressed. Furthermore, ECV secretes FL, IL-6, IL-8, G-CSF and GM-CSF, which were augmented by tumor necrosis factor-alpha and rhFL. CONCLUSIONS: rhFL enhances hematopoietic colony formation and DC proliferation from human cord blood cells. FL not only stimulates the proliferation of ECV, but is also secreted by ECV. FL may exert direct and indirect effects on hematopoiesis.

Cell Division↗
PubMed2002

Exertional rhabdomyolysis in a 4-year-old standardbred filly.

A young standardbred filly became stiff and uncomfortable after racing. A day later, creatine kinase, aspartate aminotransferase, and lactic dehydrogenase levels were markedly elevated. Exertional rhabdomyolysis was diagnosed. Limited exercise and a low carbohydrate, high fat diet were prescribed. Eight days later, the filly was raced again without consequences.

Animals↗
PubMed2002

Investigation of the effect of different regulatory peptides on adrenocortical cell proliferation in immature rats: evidence that endogenous adrenomedullin exerts a stimulating action.

Compelling evidence indicates that the active growth of immature rat adrenal glands is sustained not only by an increased release of pituitary ACTH, but also by other ancillary mechanisms. We investigated whether vasoactive intestinal peptide (VIP), atrial natriuretic peptide (ANP), adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) play a relevant role in these mechanisms. These four regulatory peptides were chosen because previous studies demonstrated that they are expressed in rat adrenals and are able to modulate the secretory activity and growth of zona glomerulosa (ZG), i.e., the adrenal layer. Groups of immature (20-day old) rats were given three subcutaneous injections (28, 16 and 4 h before sacrifice) of 2 nmol/100 g of the four peptides and/or selective antagonists of their receptors (VIP-A, ANP-A, ADM-A and PAMP-A), and 0.1 mg/100 g vincristin 3 h before autopsy. Adrenal glands were collected, processed for light microscopy, and the mitotic index (MI; percentage of metaphase-arrested cells) was evaluated in the subcapsular ZG. Neither VIP nor VIP-A affected MI. Both ANP and ANP-A decreased MI and their effects displayed additivity. ADM and PAMP raised MI and the effect was abolished by ADM-A and PAMP-A, respectively. When administered alone ADM-A, but not PAMP-A, significantly lowered MI. Collectively, our findings suggest that: i) neither VIP nor PAMP are involved in the regulation of immature rat adrenals; ii) ANP exerts a non-receptor-mediated inhibitory action, whose physiological relevance remains to be investigated; and iii) endogenous ADM system plays a relevant role in the mechanisms underlying the maintenance of high growth rate during adrenal maturation.

Adrenal Cortex↗
PubMed2002

Bauxite manufacturing residues from Gardanne (France) and Portovesme (Italy) exert different patterns of pollution and toxicity to sea urchin embryos.

This study was designed to investigate the composition and toxicity of solid residues from bauxite manufacturing plants. Soil and dust samples were collected in the proximity of two bauxite plants (Gardanne, France, and Portovesme, Italy). Samples were analyzed for their content of some selected inorganic contaminants by means of inductively coupled plasma optical emission spectroscopy (ICP-OES) either following acid digestion procedures or by seawater release of soluble components. Toxicity was tested by sea urchin bioassays to evaluate a set of toxicity endpoints including acute embryotoxicity, developmental defects, changes in sperm fertilization success, transmissible damage from sperm to the offspring, and cytogenetic abnormalities. Inorganic analysis showed two distinct sets of inorganic contaminants in Gardanne versus Portovesme, including Al, Cr, Cu, Fe, Mn, Pb, Ti, and Zn; sample composition (seawater-soluble contaminants) and toxicity showed a noteworthy association. The most severe toxicity to embryogenesis and to sperm fertilization success was exerted by some Portovesme samples (0.03-0.5% w/v), with a significant association between toxicity and dose-related seawater release of Zn, Pb, and Mn. Seawater extraction of a toxic dust sample (G20) from the Gardanne factory showed increasing seawater release of Al, Fe, and Mn; the G20 sample, at the level of 0.5%, affected both developing sea urchin embryos and sperm (offspring quality). Soil samples around the Gardanne factory showed the highest frequency of toxic soil sites eastward from the factory. The present data point to solid deposition from bauxite plants as a potential subject of environmental health concern. The results suggest that extraction methods for evaluating the toxicity of complex mixtures should be based on the environmental availability of mixture components. The differences in sample toxicity among the tested sites, however, suggest possible site-to-site variability in geochemical and/or technological parameters.

Aluminum Oxide↗
PubMed2002

Early exposure to genistein exerts long-lasting effects on the endocrine and immune systems in rats.

BACKGROUND: Although the immunologic effects of endogenous and synthetic estrogens are well studied, few studies have examined the hormonal effects of phytoestrogens (i.e., plant-derived estrogens) on the immune system. The primary goal of this study was to compare the effects of perinatal exposure with life-long exposure to genistein, an estrogenic compound in soy, on the endocrine and immune system in adulthood. MATERIALS AND METHODS: Pregnant female rats were exposed to no, low (5 mg/kg diet), or high (300 mg/kg diet) genistein diets throughout gestation and lactation. At weaning, male offspring exposed to genistein perinatally were either switched to the genistein-free diet or remained on the genistein-dosed diets. At 70 days of age, immune organ masses, lymphocyte subpopulations, cytokine concentrations, and testosterone concentrations were assessed in male offspring. RESULTS: Data were analyzed based on the diets that males were exposed to during gestation and lactation because life-long exposure to genistein had no additional effect on any of the dependent measures. Relative thymus masses were greater among males exposed to the high genistein diet than among males exposed to no genistein. Although the proportions of splenic and thymic CD4+ T cells were not altered by genistein, the percentages of CD4+CD8+ thymocytes, CD8+ splenocytes, and total T cells in the spleen were higher and the percentages of CD4-CD8- thymocytes were lower among males exposed to genistein than among males not exposed to genistein. Synthesis of interferon-gamma (IFN-gamma) was marginally higher and testosterone concentrations were lower among genistein-exposed than genistein-free males. DISCUSSION: These data illustrate that exposure to genistein during pregnancy and lactation exerts long-lasting effects on the endocrine and immune systems in adulthood. Whether exposure to phytoestrogens during early development affects responses to infectious or autoimmune diseases, as well as cancers, later in life requires investigation.

Animals↗
PubMed2003

Collapse from exertional heat illness: implications and subsequent decisions.

The implications of the collapse of a soldier early in an exercise from exertional heat illness (EHI) are considered. Such soldiers may be at risk from a genetic predisposition. Malignant hyperthermia (MH) and isolated and improbable cases of EHI may be just two different expressions of the same mutated gene sequence. The genetics of MH are complex and present knowledge is incomplete. The use of the in vitro contraction test (IVCT) on cases of EHI, in addition to its proven role in MH, would be helpful in examining the relationship between MH and EHI. It has been shown that some soldiers collapsing with EHI may have subsequent positive IVCTs. The test, however, sometimes produces false positives and, in addition, a positive result could be a consequence of a heat insult rather than an antecedent. Further studies to establish the incidence of positive IVCTs in relatives of EHI probands, and thus test for heritability, are required. There is, at the moment, only one example of proven MH and proven EHI occurring in the same individual. DNA from a 12-year-old boy who suffered MH and later died from the EHI and from his relatives showed relevant mutations as did the DNA of two of three soldiers who survived EHI. Hajj pilgrims, who collapse with heat illness, do not show such mutations, but the etiology is different. The sedentary pilgrims succumbed to a very high external ambient temperature, the active soldiers to a huge output of internal metabolic heat. Only eventual advances in defining the genetics of MH and EHI will resolve the present confusion of the relationship between the two conditions. Meanwhile, there is a need to bypass considerations of the etiology of EHI and to identify the vulnerable and handicapped soldier by exposure after an interval of time to one or more exercise tolerance tests.

Adult↗
PubMed1999

[Evaluation of the efficacy and tolerance of naftidrofuryl in patients presenting with exertional angina. Multicenter double-blind versus placebo study].

Due to its vascular and platelet 5-HT2 receptor antagonist properties and its metabolic properties, naftidrofuryl specifically counteracts local ischaemic phenomena. One of its major indications is the treatment of intermittent claudication, but it is well known that peripheral arterial disease is the sign of diffuse arterial disease, associated with particularly lethal coronary disease. Recent studies increasingly implicate serotonin (5-HT) in coronary ischaemic processes. In view of the similarities between these pathophysiological data and the characteristics of this molecule, we decide to evaluate the coronary protection afforded by naftidrofuryl and its safety. This multicentre double-blind placebo-controlled study was conducted in 51 patients over a period of one month. Inclusion criteria were stable angina with an electrically positive stress test, despite antianginal treatment either by beta-blocker or by calcium channel blocker. Follow-up comprised clinical assessment and a stress test on inclusion and at 1 month. The groups were comparable on inclusion. Overall, the results showed a greater improvement with naftidrofuryl than with reference treatment for all parameters studied. Significant differences were observed in favour of the verum group for time to onset of ST depression, the maximum level reached, the number of stress tests which became negative and the patient's global assessment. No problems of interaction with concomitant treatments, particularly beta-blockers, calcium channel blockers or antiarrhythmics was observed. This study shows that naftidrofuryl allows improvement of ergometric parameters and especially elevation of the ischaemic threshold on exertion.

Adrenergic beta-Antagonists↗
PubMed2003

Methoxyestrogens exert feedback inhibition on cytochrome P450 1A1 and 1B1.

Cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) catalyze the oxidative metabolism of 17 beta-estradiol (E2) to catechol estrogens (2-OHE2 and 4-OHE2) and estrogen quinones, which may lead to DNA damage. Catechol-O-methyltransferase catalyzes the methylation of catechol estrogens to methoxyestrogens (2-MeOE2, 2-OH-3-MeOE2, and 4-MeOE2), which simultaneously lowers the potential for DNA damage and increases the concentration of 2-MeOE2, an antiproliferative metabolite. In this study, we showed that CYP1A1 and CYP1B1 recognized as substrates both the parent hormone E2 and the methoxyestrogens. Using purified recombinant enzymes, we demonstrated that CYP1A1 and CYP1B1 O-demethylated the methoxyestrogens to catechol estrogens according to Michaelis-Menten kinetics. Both CYP1A1 and CYP1B1 demethylated 2-MeOE2 and 2-OH-3-MeOE2 to 2-OHE2, whereas CYP1B1 additionally demethylated 4-MeOE2 to 4-OHE2. Because the P450-mediated oxidation of E2 and the O-demethylation of methoxyestrogens both yielded identical catechol estrogens as products, we used deuterated E2 (E2-d4), unlabeled methoxyestrogens, and gas chromatography/mass spectrometry to examine both reactions simultaneously. Kinetic analysis revealed that methoxyestrogens acted as noncompetitive inhibitors of E2 oxidation with K(i) ranging from 27 to 153 micro M. For both enzymes, the order of inhibition by methoxyestrogens was 2-OH-3-MeOE2 > or = 2-MeOE2 > 4-MeOE2. Thus, methoxyestrogens exert feedback inhibition on CYP1A1- and CYP1B1-mediated oxidative estrogen metabolism, thereby reducing the potential for estrogen-induced DNA damage.

2-Methoxyestradiol↗
PubMedDate not supplied

Cepharanthine exerts antitumor activity on oral squamous cell carcinoma cell lines by induction of p27Kip1.

Cepharanthine is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata. The drug has been widely used for the treatment of many acute and chronic diseases and can exert antitumor effects on several human cancer cells. In this study, we examined the mechanism of the antitumor effects by cepharanthine on a human oral squamous cell carcinoma (SCC) cell line. Treatment of oral SCC cells with cepharanthine (10-20 micrograms/ml) resulted in a significant suppression of cell growth. Cepharanthine preferentially suppressed the growth of B88 cells when compared with other human oral SCC cells. Moreover, it was found, by flow cytometry analysis and Hoechst 33258 staining, that G1 arrest and DNA fragmentation occurred in cepharanthine-treated B88 cells. Furthermore, induction of p27Kip1 and reduction of cyclin E and Skp2 were detected by Western blotting. B88 tumor-bearing nude mice were treated with cepharanthine, which was administered subcutaneously (40 mg/kg/day). The cepharanthine treatment results in a significant suppression of tumor growth. Overall these results indicate that cepharanthine may inhibit the growth of human oral SCC cells by down-regulating cyclin E to induce G1 arrest through a pathway of p27Kip1 induction.

Alkaloids↗
PubMed2003

The effects of exertional heatstroke and exercise-heat acclimation on plasma beta-endorphin concentrations.

INTRODUCTION: It has been suggested that a proopiomelanocortin peptide beta-endorphin may play an important role in temperature regulation and therefore have specific heat stroke response patterns. METHODS: The purpose of this study was to examine the response patterns of plasma beta-endorphin at baseline, during a 7-d exercise-heat acclimation period (HA; 90 min x d(-1), 40 degrees C), and during a 6-h exercise-heat tolerance test (HTT; 6 h, 40 degrees C) performed before and after HA. Subjects were nine previously diagnosed heatstroke patients (P) and eight matched controls (C). No differences between the two groups were observed at rest, prior to HTT. RESULTS: Plasma beta-endorphin concentration in P significantly increased above resting values at 2, 4, and 6 h of HTT and were significantly greater than C responses. During HA tests, a significantly higher beta-endorphin concentration was observed in P before exercise on day 1 and day 7, but not on day 4. A significant increase occurred after exercise in both groups, on all days of HA; no differences were observed between the groups on days 4 and 7. DISCUSSION: These results demonstrate that the opioid peptide responses in individuals with recent exertional heatstroke were greater than control subjects during the initial 6-h HTT. Decreased physical training among P may have contributed to these results. However, 7 d of HA abolished these between-group differences by reducing the magnitude of beta-endorphin responses in P, indicative of an adaptation of pituitary function.

Acclimatization↗