Long-Term Effects of Breastfeeding,Maternal Smoking During Pregnancy,and Recurrent Lower Respiratory Tract Infections on Asthma in Children

The effect of breastfeeding on asthma is controversial, which may be explained by related and interacting early childhood risk factors. We assessed the joint effects of a risk-triad consisting of maternal smoking during pregnancy, breastfeeding for less than 3 months, and recurrent lower respiratory tract infections (RLRTI) on physician-diagnosed childhood asthma. The association was assessed in the Isle of Wight birth cohort study (1989–1990) using a repeated measurement approach with data collection at birth, and at ages 1, 2, 4, and 10 years. The population consists of 1,456 children recruited between January 1989 and February 1990. Prenatal smoking, breastfeeding for less than 3 months, and recurrent lower respiratory infections (RLRTI) were combined into eight risk-triads. Relative risks (RR) and 95% confidence intervals were estimated with a log-linear model. The risk-triad involving RLRTI in infancy, maternal smoking during pregnancy, and breastfeeding for less than 3 months showed a stronger association with asthma at ages 4 and 10 compared to other risk-triads (RR of 5.79 for any asthma at ages 1, 2, 4, and 10; and 3.1 for asthma at ages 4 and 10). Of the three individual risk factors, RLRTI appeared to be the major driver of the combined effects in the risk-triads. The effect of RLRTI on asthma was modified by breastfeeding. Breastfeeding for ≥ 3 months also attenuated the effect of prenatal smoking on asthma in children without RLRTI. A high proportion of asthma cases in childhood can be prevented by promoting breastfeeding, by preventing smoking during pregnancy, and by avoidance of recurrent lower respiratory tract infections in early childhood.     

Intrarenal arteriovenous fistula causing a "pseudonutcracker effect"

We report a case in which an intrarenal arteriovenous fistula caused the nutcracker effect. Color Doppler sonography of the left renal artery showed a peak systolic velocity of 150 cm/second and renoaortic ratio of 2.1. The left renal vein was significantly dilated, and the adjacent renal artery was kinked. A stenosis in the left renal vein at the aorto-mesenteric bifurcation was demonstrated, with a maximum velocity of 201 cm/second. Renal Doppler evaluation showed an area of high-velocity, low-resistance arterial flow consistent with an arteriovenous fistula in the inferior half of the left kidney. Angiography confirmed the fistula. The fistula was successfully occluded by coil embolization. Follow-up sonography showed almost complete obliteration of the fistula, regression of the renal vein dilatation, and a reduction in renal venous and arterial flow velocities. Given the reversibility of the fistula's effects, we suggest the term "pseudonutcracker effect" to describe this case.     

Analysis of the myocardial velocities in patients with mitral stenosis

BACKGROUND: Pure mitral stenosis (MS) affects left-ventricular performance as a result of myocardial and functional factors. We planned this study to evaluate the effect of MS on right- and left-ventricular functions using Doppler tissue imaging (DTI). METHODS: A total of 46 patients with an established diagnosis of MS (mean age: 41 +/- 11 years), and 40 age-matched healthy individuals (mean age: 40 +/- 9 years) were included in this study. Echocardiography equipped with DTI function was performed on each participant. The mitral valve area was measured. Myocardial velocities were recorded at 4 different sites (septum, lateral, anterior, and inferior) of the left ventricle, and the right-ventricular free wall annulus by DTI. The positive systolic velocity when the mitral and tricuspid ring moved toward the cardiac apex, and 2 negative diastolic velocities when the mitral annulus moved toward the base away from the apex (1 during the early phase of diastole and another in the late phase of diastole [A(m)]) were measured. The early diastolic velocity/A(m) ratio was calculated for each wall. The mean of systolic and diastolic myocardial velocities of the left ventricle was calculated. Patients with pure MS were compared with healthy participants, and the relationship of DTI variables with mitral valve area was evaluated. RESULTS: The myocardial velocities of the left ventricle indicating left-ventricular function were found to be significantly lower in patients with pure MS. Right-ventricular annulus velocities, on the other hand, were similar in both groups. A significant positive correlation could be established between mitral valve area and mean positive systolic velocity, A(m) of the left ventricle, and right-ventricular A(m) (r = 0.50, P <.001; r = 0.48, P =.001; r = 0.45, P =.002, respectively), whereas a significant negative correlation (r = -0.42, P =.004) was established for right-ventricular early diastolic velocity/A(m) ratio. CONCLUSION: This first study where pure MS was evaluated by DTI shows that MS affects left-ventricular performance on long axis. The results indicate that the decrease in left-ventricular performance is caused by both functional and myocardial factors.     

Adjustment of sweep gas flow during cardiopulmonary bypass

Cardiopulmonary bypass (CPB) is one of the major tools of cardiac surgery. However, no clear data are available for the ideal value of sweep gas flow to oxygenator during CPB. The aim of this study was to determine the best value for sweep gas flow during CPB. Thirty patients undergoing isolated CABG were randomly and equally allocated into three groups. Sweep gas flow to oxygenator was kept at 1.35 l/min/m2 in group 1, 1.60 l/min/m2 in group 2, and 2.0 l/min/m2 in group 3. All patients were operated on under the same anaesthetic regime and surgical techniques. Samples for blood gas analysis were collected at T1: before CPB; T2: 5 min after the initiation of CPB; T3: just before rewarning; and T4: at the end of rewarming. Five minutes after the initiation of CPB (T2), pCO2 decreased significantly in groups 2 and 3 compared to group 1 (p < 0.02). With the addition of hypothermia (T3), the changes in the pH and pCO2 became more profound and, in this period, the levels in group 3 patients outranged the physiologic limits, with pCO2 and pH values being 28 +/- 3 mmHg and 7.50 +/- 0.04, respectively. At the end of the rewarming period (T4), in spite of increased carbon dioxide production, pCO2 values were below the physiologic limits in groups 2 and 3. We conclude that sweep gas flow to the oxygenator should be kept between 1.35 and 1.60 l/min/m2 during CPB to avoid hypocapnia, which results in alkalosis and has hazardous effects on lung mechanics, cerebral blood flow, and the cardiovascular system.     

Comparison of maximal acid output and gastrin response to meals in Chinese and Scottish normal and duodenal ulcer subjects.

Maximal acid output (MAO) after pentagastrin stimulation and gastrin response to a standard meal was studied in 100 control and 200 duodenal ulcer subjects from each of two ethnic groups, Scots and Chinese. The acid output was significantly higher in the Scots than in the Chinese for both controls and duodenal ulcer patients. Despite correction for differences in body stature by expressing MAO as a function of the body weight, these differences persisted. In 45 pairs of closely matched patients with duodenal ulcer, the differences between the two ethnic groups remained significant, irrespective of whether MAO was expressed in absolute or weight corrected values. This indicates that differences in age, sex, family history, or duration of illness did not account for differences in acid output. In 20 pairs of normal control and 45 pairs of duodenal ulcer patients the fasting and post-prandial serum gastrin levels did not differ, significantly between the two ethnic groups. The proportion of acid normosecretors was significantly higher in the Chinese duodenal ulcer patients than in the Scottish. The reason for these differences in the gastric acid output between the two ethnic groups is not known and needs to be studied further.     

Effect of ellagic acid on hepatic and pulmonary xenobiotic metabolism in mice: studies on the mechanism of its anticarcinogenic action

Our recent studies have shown that ellagic acid, a naturallyoccurring dietary plant phenol, protects BALB/c mice against3-methylcholanthrene-induced skin tumorigenesis. To furtherelucidate the mechanism of the antineoplastic action of ellagicacid its effect on hepatic and pulmonary benzo[a]pyrene (BP)metabolism, cytochrome P-450-dependent monooxygenases and glutathioneS-transferase activities were studied in BALB/c mice. Chronicoral feeding of the compound in drinking water (0.3 mg/1 for16 weeks) or acute intraperitoneal administration (50 mg/kgfor five consecutive days) of ellagic acid resulted in 20–25%decreases in hepatic and pulmonary cytochrome P-450 levels.Hepatic and pulmonary aryl hydrocarbon hydroxylase and 7-ethoxycoumarinO-deethylase activities in both groups of ellagic acid-treatedanimals were 33–52% and 28–43% lower than theirrespective non-ellagic acid-treated controls. Hepatic as wellas pulmonary aminopyrine N-demethylase and epoxide hydrolaseactivities were unchanged in both groups of ellagic acid-treatedmice. Hepatic glutathione S-transferase activity towards BP-4,5-oxide or l-chloro-2, 4-dinitrobenzene as substrates was foundto be enhanced 51 – 79% and 38–58% in both groupsof animals. H.p.l.c. analysis of organic solvent-soluble metabolitesof BP by liver and lung microsomes indicated a substantial inhibitionof diol formation (including BP-7, 8-diol), as well as of phenolsand quinones. In liver, these inhibitory effects were more pronouncedafter oral feeding than after intraperitoneal administration.Our results indicate that both acute and chronic administrationof ellagic acid inhibits BP metabolism and/or enhances glutathioneS-transferase activity. Thus the modulation of polycyclic aromatichydrocarbon metabolism by ellagic acid may be related to theanticarcinogenic effects of this compound.     

Effect of human chorionic gonadotropin in the gene expression profile of MCF-7 cells

The preventive effect of human chorionic gonadotropin (hCG)-induced differentiation on experimental mammary carcinogenesis has been reported to be due to the inhibition of cell proliferation, increased DNA repair capabilities of the mammary epithelium, decreased binding of the carcinogen to the DNA and activation of programmed cell death genes leading to apoptosis. To further our understanding of the molecular pathway of the hCG action on mammary epithelial cells we have analyzed gene expression profiles of MCF-7 cells treated with hCG for 24, 48, and 96 h, using a DNA microarray consisting of 1176 genes. Comparison of expression between the treated and not treated cells enabled us to identify 48 genes that are affected by this hormone. Importantly, there is a cluster of genes that are overexpressed during the first 24 h and level off thereafter, whereas other genes are maximally expressed at 96 h of treatment. The results obtained in this study demonstrated that genes regulating cell proliferation, apoptosis, cell trafficking, and DNA repair are significantly affected by hCG in human breast cancer cells in vitro.     

Effects of 10alpha,25-dihydroxyvitamin D3 on doxorubicin-induced chromosomal aberrations in rat bone marrow cells

The present study was carried out to evaluate the effects of 1alpha,25-dihydroxyvitamin D3 (VD) on chromosomal aberrations induced by doxorubicin (DXR). Wistar rats were divided into eight experimental groups of five animals each. Control group animals were treated with i.p. distilled water. The animals in three VD groups were given only VD for 4, 6 or 8 weeks. In the DXR groups the animals were given only DXR. In the combination groups VD doses were given for 4, 6 or 8 weeks for each group and DXR was injected 24 h before sacrificing the rats. DXR (50 mg/100 g b.w.) was injected intraperitoneally and VD by gavage 3 microg/kg/day twice weekly. Animals treated with both VD and DXR showed a low frequency of chromosomal aberrations and abnormal metaphases when compared with animals treated with DXR alone (p < 0.0001). The numbers of both chromosomal aberrations and abnormal metaphases were similar in weeks 6 and 8 (p > 0.05) and lower than those in week 4 for the VD groups (p < 0.0001). Under the present experimental conditions, the efficiency of VD in protecting cells against DXR-induced chromosome damage was found to be dose dependent. The protective effects of VD on chromosome aberrations induced by DXR are discussed in the light of literature data.     

Suppression of prostate carcinogenesis by dietary supplementation of celecoxib in transgenic adenocarcinoma of the mouse prostate model

Epidemiological studies and clinical observations suggest that nonsteroidal anti-inflammatory drugs and certain selective cyclooxygenase (COX)-2 inhibitors may reduce the relative risk of clinically evident prostate cancer. This prompted us to investigate the chemopreventive potential of celecoxib, a selective COX-2 inhibitor, against prostate carcinogenesis in a transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Similar to prostate cancer in humans, prostate malignancies in TRAMP mice progress from precursor intraepithelial lesions, to invasive carcinoma that metastasizes to lymph nodes, liver, lungs, and occasionally to bone. The basal enzyme activity and protein expression of COX-2 is significantly higher (>4-fold) in the dorsolateral prostate of TRAMP mice up to 24 weeks of age compared with their nontransgenic littermates. Eight-week-old TRAMP mice were randomly divided and fed either control diet (AIN 76A) or a custom prepared AIN 76A diet containing 1500-ppm celecoxib ad libitum for 24 weeks, a dosage that would compare with the normal recommended dose for the treatment of human disease. Studies from two independent experiments, each consisting of 10 mice on test, showed that the cumulative incidence of prostate cancer development at 32 weeks of age in animals fed with AIN 76A diet was 100% (20 of 20) as observed by tumor palpation, whereas 65% (13 of 20), 35% (7 of 20), and 20% (4 of 20) of the animals exhibited distant site metastases to lymph nodes, lungs, and liver. Celecoxib supplementation to TRAMP mice from 8-32 weeks of age exhibited significant reduction in tumor development (5 of 20) with no signs of metastasis. Celecoxib feeding resulted in a significant decrease in prostate (56%; P < 0.0003) and genitourinary weight (48%; P < 0.008). Sequential magnetic resonance imaging analysis of celecoxib-fed mice documented lower prostate volume compared with the AIN 76A-fed group. Histopathological examination of celecoxib-fed animals showed reduced proliferation, and down-modulation of COX-2 and prostaglandin E2 levels in the dorsolateral prostate and plasma, respectively. These results correlated with retention of antimetastasis markers, viz E-cadherin, and alpha- and beta-catenin, along with a significant decrease in vascular endothelial growth factor protein expression. Celecoxib supplementation also resulted in enhanced in vivo apoptosis in the prostate as monitored by several techniques including a recently perfected technique of 99mTc-labeled annexin V in live animals followed by phosphor imaging. One striking observation in an additional study was that celecoxib feeding to mice with established tumors (16 weeks of age) significantly improved their overall survival (P = 0.014), compared with AIN 76A-fed group. Our findings suggest that celecoxib may be useful in chemoprevention of prostate cancer.     

The effect of mineral trioxide aggregate on the contractility of the rat thoracic aorta

Mineral trioxide aggregate (MTA) is being advocated for vital pulp therapy. In the case of direct pulp capping, hemorrhage control is an important step on success, but little is known about the effect of MTA on pulpal bleeding. In addition, there has been a lack of information on the effect of MTA on smooth muscle contraction, such as can occur in the blood vessels of dental pulp. The present study assessed the vascular effects of MTA, using the rat aortic ring preparations as a tissue model. MTA (100-500 mg) induced dose-dependent contraction in rat thoracic aorta. The contractile effect of MTA was blocked by calcium channel blocker nifedipine (1 muM). These data suggest that the vasoconstrictor property of MTA is related to calcium influx and it may allow proper control of hemorrhage which is critical for the success of any pulp-capping treatment.