Inhibitory effect of sarcophytol A on pancreatic carcinogenesis after initiation by N-nitrosobis(2-oxypropyl)amine in Syrian hamsters

Sarcophytol A (SaA), a cembrane-type diterpene, inhibits pancreatic carcinogenesis induced by N-nitrosobis(2-oxypropyl)amine (BOP) in hamsters. The experimental groups received two injections of BOP at 70 mg/kg dose, followed 2 weeks later by a 20 mg/kg dose injection, and were fed a basal diet or 0.01 and 0.05% SaA diets starting 1 week after the second injection of BOP. Control groups were injected with normal saline and fed the basal diet or the 0.05% SaA diet. All animals were killed 30 weeks after the start of the experiments. Seventeen BOP-treated hamsters fed the basal diet developed pancreatic tumors (77.3%) while only 12 of 21 hamsters fed the 0.01% SaA diet (57.1%) and 12 of 23 hamsters fed the 0.05% SaA diet (52.2%) developed pancreatic tumors. Pancreatic lesions included ductal hyperplasia, atypical ductal hyperplasia, and carcinoma in situ. Microscopic invasive carcinoma induced by BOP and the incidence of larger pancreatic tumors in hamsters were significantly higher in hamsters fed the basal diet than in hamsters fed the SaA diet (p < 0.05). The proliferating cell nuclear antigen (PCNA) labeling index of pancreatic carcinoma in BOP-treated hamsters fed the basal diet was 41.2 +/- 13.4%, whereas BOP-treated hamsters fed 0.01 and 0.05% SaA diets yielded PCNA indexes of 26.8 +/- 8.3 and 28.4 +/- 7.0%, respectively. k-ras mutation was detected in 40% of cancers in both groups. No pancreatic tumors developed in saline-treated groups, and no differences in body weights or histological findings in their organs, including the pancreas, were observed in either group. These findings suggest that SaA not only inhibits BOP-induced pancreatic carcinogenesis in hamsters, but also provides antipromotion and antiprogression effects on these tumors, even when SaA commences 1 week after the initiation of pancreatic carcinogenesis.     

Angiotensin II receptor blockade in Syrian hamster (T0-2) cardiomyopathy does not affect microscopic cardiac material properties: implications for mechanisms of tissue remodeling

This study delineates the role of angiotensin II type I (AT1) receptor in the remodeling of Syrian cardiomyopathic hamsters. Twelve cardiomyopathic (T0-2) hamsters received L-158,809 treatment and libitum in their drinking water (27 micrograms/ml) and 9 cardiomyopathic and 9 normal FL-B hamsters received tap water from 1 to 4 months of age. Although pharmacologically effective with regard to complete suppression of the blood pressure response to angiotensin II infusion, L-158,809 did not diminish the progression or severity of cardiomyopathy. Heart weight/100 g body weight and left ventricular wall thickness adjusted for body weight of both L-158,809 and cardiomyopathic control hamsters did not differ and exceeded those of F1-B controls (p < 0.05). Myocardial material properties (e.g., stiffness and density) of cardiomyopathic hamsters treated with L-158,809 were not affected. Thus, the progression of fibrosis, calcification, and necrosis in T0-2 cardiomyopathic hamsters was not sensitive to AT1 receptor blockade.     

Dietary protein restriction and selective preference for a protein-containing diet in the golden hamster (Mesocricetus auratus)

The corrected midparental height method was introduced by Tanner in 1970 (Tanner method) and is commonly used to estimate target height in children to evaluate the effectiveness of growth-promoting therapies. It has not been established if the equation used to compute target height should be the same for children with short, normal, or tall parents. In this study, we examined the predicted target height values by parental heights in a large population-based study (n = 2402). A simple linear function of midparental height (x) was proposed to estimate target height (y): y = 45.99 + 0.78x (boys), y = 37.85+0.75x (girls), with a 95% predicted interval of about +/-10 cm. The prediction model was similar for boys and girls in SD scores (SDS), and was not affected by assortative mating or difference in parental heights. The model may underestimate the potential stature by about 2 cm for children with midparental height below -2 SDS, or 163 cm. In comparison, the Tanner method may lead to a 6-cm error in underestimating target height for these children. The function would be a better choice than the Tanner method for estimating target height in the clinical evaluation of growth promotion treatments because it is common that short children also have short parents. Children with very short parents will usually be much taller than their parents in adult stature, and we believe that a different function should be developed. The results support the proposed nondominant, non-sex-linked, polygenic inheritance in stature. The estimated heritability values were 0.75-0.78 in cm or 0.55-0.60 in SDS.     

Promotional effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) on N-nitrosobis(2-oxopropyl)amine (BOP)-initiated carcinogenesis in hamsters

The effects of administration of low doses of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific nitrosamine, were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Female Syrian golden hamsters were given a single sc injection of BOP at a dose of 10 mg/kg and then administered 2 or 5 ppm NNAL in their drinking water for 52 wk. Additional groups of animals received the BOP injection alone, or only the 2 or 5 ppm NNAL treatments as BOP-negative controls. At wk 53 of the experiment, all surviving animals were killed and the development of proliferative lesions was assessed histopathologically. The total incidence of combined carcinomatous and dysplastic lesions of the exocrine pancreas was significantly higher (P < 0.05) in the BOP/NNAL 5 ppm group than in the BOP alone group, although there was no statistically significant influence of NNAL on the development of either pancreatic adenocarcinomas or dysplastic lesions viewed singly. The treatments with NNAL alone did not induce any proliferative lesions of the exocrine pancreas. No significant intergroup differences were found in either incidence or multiplicity of islet cell proliferative lesions. Immunohistochemical examination of islet cell proliferative lesions (hyperplasias and adenomas) found in the BOP-treated animals showed no significant differences in pancreatic hormone production between NNAL-treated and -untreated groups. The NNAL treatment did not exert any influence on lung, liver or kidney tumorigenesis. Thus, the results suggest that NNAL enhances BOP-induced exocrine but not endocrine pancreatic tumorigenesis in hamsters when given in the post-initiation phase.     

Daily and photoperiodic 2-125I-melatonin binding changes in the pars tuberalis of the Syrian hamster (Mesocricetus auratus): effect of constant light exposure and pinealectomy

To clarify the relationship between neural crest cells and various developmental eye abnormalities, pregnant mice were administered an intraperitoneal injection of 12.5 mg/kg retinoic acid (RA) suspended in corn oil on day 7 of pregnancy (RA group). Control mice received an equal volume of corn oil only (control group). The fetuses were removed by laparotomy on day 18 of gestation. The fetal mortality was 46.3% in the RA group and 2.2% in the control group. The live fetuses in both groups were observed grossly, and the eyes were examined histologically in serial sections. In the RA group, gross malformations were observed, including microphthalmos (95.5%), cleft lip and palate (36.4%), and central nervous system anomalies (31.8%). In the control group, these malformations were seen in only 6.7%, 0%, and 2.2%, respectively. Histologic examinations in the RA group revealed microphthalmos (47.7%), anophthalmos (38.6%), faulty closure of the embryonic fissure (36.4%), developmental abnormalities of the vitreous (34.1%), aphakia (22.7%), goniodysgenesis (18.2%), and faulty separation of the lens vesicle (15.9%). They were detected in only 3.3%, 1.1%, 3.3%, 8.9%, 1.l%, 2.2%, and 2.2%, respectively, of the control group. These developmental eye abnormalities arose from abnormal migration of neural crest cells.     

Chemoprevention of azoxymethane-induced intestinal carcinogenesis by a novel synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, in rats

The present study was designed to investigate the modifying effects of dietary 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone (KYN-54), a new synthetic retinoidal butenolide, during the post-initiation phase on azoxymethane (AOM)-induced rat intestinal carcinogenesis. The number of aberrant crypt foci (ACF) in rat colon, colonic ornithine decarboxylase (ODC) activity and bromodeoxy-uridine (BrdUrd) labeling index in rat colonic epithelium were also assessed. At 7 weeks of age, male F344 rats (except the KYN-54 alone and control groups) were given weekly s.c. injections of AOM at 15 mg/kg body wt for 3 weeks. Starting 1 week after the last injection of AOM, rats (except the control group) were fed a diet containing KYN-54 at concentrations of 100 or 200 p.p.m. throughout the experiment. All animals were necropsied at 32 weeks after the start of the experiment. Compared with the AOM alone group, KYN-54 at both doses reduced the incidence and multiplicity of tumors in entire intestine (small and large intestines). In the 200 p.p.m. KYN-54 fed group especially, tumor incidence and multiplicity in the entire intestine were lower compared with the AOM alone group (P < 0.005 and P < 0.05 respectively). Also, the number of ACF/cm2 colon in the groups of rats treated with AOM and KYN-54 at both doses were significantly lower than that of rats treated with AOM alone (P < 0.05). Colonic ODC activity and BrdUrd labeling index in the groups of rats treated with AOM and KYN-54 at both doses were slightly lower than those treated with AOM alone. KYN-54 at 200 p.p.m. significantly lowered BrdUrd labeling index induced by AOM (P < 0.005). These results suggest that KYN-54 might be a promising chemopreventive agent for intestinal neoplasia.     

Peripheral O2 diffusion does not affect V(O2)on-kinetics in isolated insitu canine muscle

To test the hypothesis that muscle O2 uptake (V(O2)) on-kinetics is limited, at least in part, by peripheral O2 diffusion, we determined the V(O2) on-kinetics in 1) normoxia (Control); 2) hyperoxic gas breathing (Hyperoxia); and 3) hyperoxia and the administration of a drug (RSR-13, Allos Therapeutics), which right-shifts the Hb-O2 dissociation curve (Hyperoxia+RSR-13). The study was conducted in isolated canine gastrocnemius muscles (n = 5) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60-70% peak V(O2)). In all conditions, before and during contractions, muscle was pump perfused with constantly elevated blood flow (Q), at a level measured at steady state during contractions in preliminary trials with spontaneous Q x Adenosine was infused intra-arterially to prevent inordinate pressure increases with the elevated Q x Q was measured continuously, arterial and popliteal venous O2 concentrations were determined at rest and at 5- to 7-s intervals during contractions, and V(O2) was calculated as Q x arteriovenous O2 content difference. PO2 at 50% HbO2 saturation (P50) was calculated. Mean capillary PO2 (Pc(O2)) was estimated by numerical integration. P50 was higher in Hyperoxia+RSR-13 [40 +/- 1 (SE) Torr] than in Control and in Hyperoxia (31 +/- 1 Torr). After 15 s of contractions, Pc(O2) was higher in Hyperoxia (97 +/- 9 Torr) vs. Control (53 +/- 3 Torr) and in Hyperoxia+RSR-13 (197 +/- 39 Torr) vs. Hyperoxia. The time to reach 63% of the difference between baseline and steady-state V(O2) during contractions was 24.7 +/- 2.7 s in Control, 26.3 +/- 0.8 s in Hyperoxia, and 24.7 +/- 1.1 s in Hyperoxia+RSR-13 (not significant). Enhancement of peripheral O2 diffusion (obtained by increased PcO2 at constant O2 delivery) during the rest-to-contraction (60-70% of peak V(O2)) transition did not affect muscle V(O2) on- kinetics.     

Kinds of mutations induced by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in the hprt gene of Chinese hamster ovary cells

The kinds of mutations induced by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in the protein coding region of the hprt gene of Chinese hamster ovary (CHO) cells were determined by direct sequencing of polymerase chain reaction (PCR)-amplified cDNA. Primary mutations were found in 15 of 19 of the mutants: 11 were G:C-->T:A transversions, two were A:T-->T:A transversions and two were deletions of single G:C base pairs (-1 frameshifts). The remaining four mutants had large alterations in the cDNA that were explained by mRNA splicing errors. A group of control mutants had more diverse hprt cDNA alterations than MX-induced mutants. Transversions yielding an A:T base pair were the predominant type of MX-induced mutations, in agreement with previous findings in bacteria. This specificity may be explained by the 'A rule', that DNA polymerases preferentially insert adenine nucleotides opposite non-instructional lesions.     

Cytotoxic amyloid peptides inhibit cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction by enhancing MTT formazan exocytosis

Amyloid beta peptide (A beta) neurotoxicity is believed to play a central role in the pathogenesis of Alzheimer's disease. An early indicator of A beta toxicity is the inhibition of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction to MTT formazan, a widely used assay for measuring cell viability. In this report we show that A beta and other cytotoxic amyloid peptides such as human amylin dramatically enhance MTT formazan exocytosis, resulting in the inhibition of cellular MTT reduction. Only the amyloid peptides that are known to be cytotoxic enhanced MTT formazan exocytosis. Basal MTT formazan exocytosis and amyloid peptide-enhanced MTT formazan exocytosis are blocked by several drugs with diverse known effects. These and other data suggest that MTT formazan exocytosis is a multistep process and that cytotoxic amyloid peptides enhance MTT formazan exocytosis through an intracellular signal transduction pathway.     

Analysis of a polymorphism in the tuberous sclerosis (TSC2) gene does not predispose to schizophrenia

The tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of malformations in various organs including the brain. A polymorphism in the TSC2 gene has been found to be increased in gangliogliomas, a lesion which is associated with disturbed neuro-glial cell migration pattern. Since these pathomorphological changes are compatible with disturbed neuronal migration in schizophrenic brains, we investigated this polymorphism in 130 families with a schizophrenic index patient. A 222-bp fragment of genomic DNA containing the TSC2 variant was analyzed by SSCP. The analysis revealed that there is no association with schizophrenia.     

The Th1 to Th2 shift induced by Schistosoma mansoni does not exacerbate murine aids (MAIDS)

Schistosoma mansoni infection in mice is associated with a switch from a Th1 to a Th2-type cytokine response. The role of Th1 and Th2 responses in immune dysregulations associated with AIDS and murine AIDS (MAIDS) is controversial, but a Th2 bias could be associated with disease progression, raising the hypothesis that helminth infections might accelerate the retroviral disease progression. Here, we used the murine model of AIDS to evaluate the course of the viral disease during co-infection with S. mansoni. C57BL/6 mice were infected with S. mansoni cercariae 8 weeks before intravenous challenge with the LP-BM5 retroviral complex. MAIDS did not progress faster in co-infected mice, in terms of spleen and inguinal lymphadenopathy size, ecotropic virus titres in the spleen, or in vitro proliferative responses to mitogen. Th2 cytokine production was not enhanced in co-infected animals, except for an isolated increase in IL-4 production 21 weeks after LP-BM5 infection. Co-infected animals had significantly lower lymph node and spleen weights than mice infected with LP-BM5 only. MAIDS did not influence the granulomatous response to S. mansoni in the liver of co-infected mice. Finally, infection with S. mansoni neither enhanced Th2 cytokine production nor accelerated MAIDS progression in animals subsequently challenged with LP-BM5.     

The effect of Gynostemma pentaphyllum mak (GP) on carcinogenesis of the golden hamster cheek pouch induced by DMBA]

AIM: of this study is to compare two similar groups presenting inguinal herniae, one group having laparoscopic herniography and the other having a Bassini or Fruchaud repair. METHOD: Since September 1994, in our department, patients presenting with symptoms of unilateral or bilateral inguinal herniae to our practice were offered the transperitoneal or preperitoneal approach as an alternative of open surgical repair. We considered the first 50 patients operated by laparoscopic technic (35 M and 15 F), age between 22-72 years (group A), and similar group operated by Bassini or Fruchaud technic (group B). All the patients had general anesthesia and perioperative antibiotics. In the group A we used Prolene, Mercilene or Plastex mesh. The following parameters were assessed: 1) operative time from incision to closure: 2) amount and type of analgesia required postoperatively; 3) morbidity related to the procedure; 4) interval before returning to full activity; 5) early recurrence rate; 6) hospital cost. RESULTS: The mean operative time for unilateral herniae in group A was 70 +/- 10 minutes versus 40 +/- 12 minutes in group B. Group A required to return to work was significantly shorter for the patients in group A (7 +/- 3 days) compared with group B patients (25 +/- 10 days). Although no recurrent herniae have yet been found in patients from either group; follow-up was only 2-18 months in the two groups. The cost of hospital care of group A patients exceeded that of group B by approximately 1.7 more. IN CONCLUSION: was consider that although is more expensive, the laparoscopic procedure in treatment of inguinal herniae, has more benefits for the patients.     

Construction of Syrian hamster lines congenic at the polymorphic acetyltransferase locus (NAT2): acetylator genotype-dependent N- and O-acetylation of arylamine carcinogens

Congenic Bio. 1.5/H-NAT2 Syrian hamster lines were constructed by introducing the NAT2r gene from MHA/SsLak inbred hamsters into a background BIO 1.5 Syrian inbred hamster line. Genetic identity of the Bio. 1.5/H-NAT2 congenic lines and nonidentity with the previously constructed Bio. 82.73/H-Pat congenic lines were determined by "DNA fingerprints" of genomic DNA derived from the different hamster lines. The N-acetylation capacity of the Bio. 1.5/H-NAT2 congenic hamster lines was clearly NAT2-dependent both in vivo and in vitro, with highest levels expressed in Bio. 1.5/H-NAT2r homozygous rapid acetylators, intermediate levels in Bio. 1.5/H-NAT2r/NAT2s heterozygous acetylators, and lowest levels in Bio. 1.5/H-NAT2s homozygous slow acetylators. The NAT2-dependent expression of N-acetyltransferase activity was evident toward p-aminobenzoic acid, 4-aminophenol, 2-aminofluorene, 4-aminobiphenyl, beta-naphthylamine, and 3,2'-dimethyl-4-amino-biphenyl in liver, kidney, colon, lung, and urinary bladder cytosols. The polymorphic acetyltransferase (NAT2) and the monomorphic acetyltransferase (NAT1) were isolated from hepatic cytosols and tested separately for their ability to catalyze arylamine N-acetyltransferase and N-hydroxyarylamine O-acetyltransferase activities. Both arylamine N-acetylation and N-hydroxyarylamine O-acetylation were clearly acetylator genotype-dependent when catalyzed by NAT2, and both were clearly acetylator genotype-independent when catalyzed by NAT1. NAT2/NAT1 activity ratios varied with the particular arylamine substrate acetylated. These studies show an important role for NAT2 acetylator genotype in Syrian hamster carcinogenic arylamine metabolism and confirm its role in the metabolic activation of N-hydroxyarylamines. The Bio. 1.5/H-NAT2 congenic lines provide a new model for investigating the precise role of the NAT2 gene locus in arylamine metabolism and toxicity.     

Nicotine given intracerebroventricularly does not inhibit the preovulatory surge of LH and PRL secretion in female rats

Twenty-three cases of Little Leaguer's shoulder were reviewed including the history and physical examination findings, as well as bilateral internal and external rotation anteroposterior comparison radiographs of the proximal humerus. The average follow-up was 9.6 months (range, 1.5 to 54), and all patients were observed until they had either returned to baseball or their symptoms had resolved. The average age of the patients in this series was 14 years. The chief complaint in all patients was pain localizing to the proximal humerus during the act of throwing. The average duration of symptoms was 7.7 months. Nineteen patients (83%) were pitchers. Physical examination revealed tenderness to palpation over the proximal humerus in 20 patients (87%), with 16 (70%) demonstrating specific tenderness over the lateral aspect of the proximal humerus. Swelling, weakness, atrophy, and loss of motion were uncommon findings. All 23 patients demonstrated radiographic widening of the proximal humeral physis of the throwing arm on internal and external rotation comparison anteroposterior radiographs of the shoulder. All patients were treated with rest from baseball throwing for an average of 3 months. Twenty-one of the 23 patients (91%) returned to playing baseball and were asymptomatic. The classic radiographic finding of widening of the proximal humeral physis can easily be seen on bilateral anteroposterior internal and external rotation radiographs of the proximal humerus. Rest from throwing for at least 3 months is recommended, followed by a gradual return to throwing in an asymptomatic shoulder.     

Chronic protein restriction does not alter energetic efficiency or brown adipose tissue thermogenic capacity in genetically obese (fa/fa) Zucker rats

Attenuated regulatory thermogenesis in genetically obese (fa/fa) Zucker rats involves an impaired capacity to increase sympathetic drive to brown adipose tissue in response to dietary stimuli. Young, growing lean rats fed a low protein diet reduce energetic efficiency to compensate for elevated energy intake; however, it is not known if obese rats adapt similarly to chronic protein restriction by decreasing energetic efficiency and whether this would be accompanied by increased brown adipose tissue thermogenic capacity. Lean (Fa/Fa) and obese Zucker rats were either protein-restricted (protein 8% of total energy) or fed a control diet (21% protein) starting at age 5 wk. At 9 wk, oxygen consumption (VO2) was measured in response to an intubated meal of mixed macronutrient composition. Mass-adjusted food intake (i.e., food intake/body weight 0.67) was greater in protein-restricted than in control lean rats, but not different due to diet in obese rats. Mass-adjusted brown adipose tissue uncoupling protein levels were more than 100% greater in protein-restricted vs. control lean rats, but not different between protein-restricted and control obese rats. The uncoupling protein level was not significantly different in control lean vs. obese rats. Energetic efficiency was 40% lower in protein-restricted vs. control lean, but not different in obese rats; however, the efficiency of protein utilization was significantly greater in obese protein-restricted than in obese control rats. Meal-induced energy expenditure (VO2) did not differ significantly due to diet or genotype. In conclusion, protein restriction led to overfeeding in lean rats which appeared to enhance brown adipose tissue thermogenic capacity and decrease energetic efficiency. Protein efficiency increased to more than two times its original value in obese (fa/fa) rats, but otherwise no metabolic accommodation in the capacity for regulatory thermogenesis was observed in this genotype.     

Tyrosine hydroxylase- and/or aromatic L-amino acid decarboxylase-containing cells in the suprachiasmatic nucleus of the Syrian hamster (Mesocricetus auratus)

We assessed forearm vascular and blood pressure responses to dynamic leg exercise in patients 7 and 28 days postmyocardial infarction. To determine a possible association between abnormal exercise vascular responses and baroreflex dysfunction, integrated and carotid baroreflex sensitivity and forearm vascular responses (during application of subhypotensive lower body negative pressure) were assessed. On day 7, 42 patients were compared with 21 age- and sex-matched controls. All subjects were assessed for (1) forearm vascular resistance during semierect exercise, (2) blood pressure measurements during erect treadmill exercise, and (3) integrated, cardiopulmonary, and carotid baroreceptor sensitivity. These studies were repeated in 13 patients on day 28. Forearm vascular resistance increased during exercise by 36% +/- 63% in patients versus 121% +/- 105% in controls (P = 0.0001), and fell in 15 patients, a response seen in none of the controls. Exercise hypotension was demonstrated in 5 patients, all of whom had abnormal vasodilator vascular responses. Those patients with vasodilator responses had a lower left ventricular ejection fraction (52% +/- 12% vs 62% +/- 9%; P = 0.007), and lower cardiopulmonary mechanoreceptor sensitivity (-6.6 +/- 3.9 units vs +6.4 +/- 10.4 units, P = 0.02) than those with constrictor responses, respectively. In the 13 patients studied on day 28, the change in forearm vascular resistance was similar to that observed on day 7 (36% +/- 63% vs 46% +/- 73%). Paradoxical vasodilation of forearm vessels during leg exercise is common in patients studied 7 and 28 days postmyocardial infarction, and is associated with lower left ventricular ejection fraction and abnormal vascular responses during subhypotensive lower body negative pressure.     

The -514 polymorphism in the hepatic lipase gene (LIPC) does not influence androgen-mediated stimulation of hepatic lipase activity

The -514T allele of hepatic lipase is associated with increased high density lipoprotein-cholesterol levels in men, but not in women. This observation suggests that the -514C to T polymorphism may diminish the response of hepatic lipase to androgens. To test this hypothesis, five -514T and five -514C homozygous men were treated with the anabolic steroid stanozolol for 6 days. The mean increase in hepatic lipase activity was similar in the two groups (45+/-10 vs. 51+/-10 mmol x hr(-1) x l(-1), P = 0.5). To evaluate the association between the -514 polymorphism and hepatic lipase activity at different physiological androgen concentrations, hepatic lipase genotypes and activities were measured in 44 men and 40 premenopausal women. The effect of the -514T allele on hepatic lipase activity was significant and quantitatively similar in both sexes. These data indicate that the -514 polymorphism does not influence the response of hepatic lipase activity to androgens, and that the effects of this polymorphism on hepatic lipase activity are independent of androgen action.     

Dysregulation of ornithine decarboxylase activity, apoptosis and Bcl-2 oncoprotein in Syrian hamster embryo cells stage-exposed to di(2-ethylhexyl)phthalate and tetradecanoylphorbol acetate

Perturbations of cell proliferation and death are considered as essential events in the process of carcinogenesis. Thus, two parameters, ornithine decarboxylase (ODC), an enzyme closely related to cell proliferation and transformation, and apoptotic phenomenon are profoundly modified. Using Syrian hamster embryo (SHE) cells, we have examined in the framework of two-stage carcinogenesis (initiation-promotion) the effects of a non-genotoxic [diethylhexylphthalate (DEHP)] or genotoxic [benzo[a]pyrene (BaP)] carcinogen or a non-carcinogenic compound [phthalic anhydride (AP)] on these parameters. Immunoreactive Bcl-2 and Bcl-xL proteins were also investigated following two-stage exposures. Whereas exposures to BaP, DEHP or AP alone did not provoke any modification of ODC activity, the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), strongly increased it. Using two-stage exposure protocol (xenobiotics first, then replacement by TPA-promoter), the ODC activity was higher than that obtained with TPA alone. This superinduction of ODC activity was observed only with the carcinogenic compounds DEHP and BaP. Following the same exposure protocol, spontaneous cellular apoptosis was decreased. Furthermore, Bcl-2 oncoprotein was also upregulated approximately 8- and 11-fold for BaP and DEHP respectively; meanwhile Bcl-xL protein rate did not change. The non-carcinogenic compound AP slightly inhibited spontaneous SHE cell death without ODC superinduction. Exogenous polyamines, putrescine, spermidine and spermine diluted in the medium did not inhibit spontaneous apoptosis. Although inhibition of apoptosis was not specific of carcinogenic compound, both superinduction of ODC activity and inhibition of apoptosis via Bcl-2 upregulation, may cooperate during early stages of the carcinogenic process.     

Faster adjustment of O2 delivery does not affect V(O2) on-kinetics in isolated in situ canine muscle

The mechanism(s) limiting muscle O2 uptake (VO2) kinetics was investigated in isolated canine gastrocnemius muscles (n = 7) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60-70% of peak V(O2)). Two conditions were mainly compared: 1) spontaneous adjustment of blood flow (Q) [control, spontaneous Q (C Spont)]; and 2) pump-perfused Q, adjusted approximately 15 s before contractions at a constant level corresponding to the steady-state value during contractions in C Spont [faster adjustment of O2 delivery (Fast O2 Delivery)]. During Fast O2 Delivery, 1-2 ml/min of 10(-2) M adenosine were infused intra-arterially to prevent inordinate pressure increases with the elevated Q. The purpose of the study was to determine whether a faster adjustment of O2 delivery would affect V(O2) kinetics. Q was measured continuously; arterial (Ca(O2)) and popliteal venous (Cv(O2)) O2 contents were determined at rest and at 5- to 7-s intervals during contractions; O2 delivery was calculated as Q x Ca(O2), and V(O2) was calculated as Q x arteriovenous O2 content difference. Times to reach 63% of the difference between baseline and steady-state VO2 during contractions were 23.8 +/- 2.0 (SE) s in C Spont and 21.8 +/- 0.9 s in Fast O2 Delivery (not significant). In the present experimental model, elimination of any delay in O2 delivery during the rest-to-contraction transition did not affect muscle V(O2) kinetics, which suggests that this kinetics was mainly set by an intrinsic inertia of oxidative metabolism.     

Variable distribution of TFF2 (Spasmolysin) alleles in Europeans does not indicate predisposition to gastric cancer

Multiple and eruptive dermatofibromas are, on the contrary, unusual. Often the patients who show this peculiar cutaneous pattern are referred for immunosuppressive therapy or they have an immunosuppressive disease. We report the case of a woman affected by mycosis fungoides, who developed, in 2 months, 14 dermatofibromas on her legs. The personal history of the patient revealed a previous immunosuppressive treatment with systemic corticosteroids for interstitial pneumonia. Different etiological hypothesis have been proposed to explain the eruptive presence of multiple dermatofibromas and the alteration of the immune response, but the real mechanism is still unclear. Dermatofibromas are benign tumours usually encountered in dermatology.