Comparative pulmonary absorption, distribution, and toxicity of copper gallium diselenide, copper indium diselenide, and cadmium telluride in Sprague-Dawley rats

Copper gallium diselenide (CGS), copper indium diselenide (CIS), and cadmium telluride (CdTe) are novel compounds used in the photovoltaic and semiconductor industries. This study was conducted to characterize the relative toxicities of these compounds and to evaluate the pulmonary absorption and distribution after intratracheal instillation. Female Sprague-Dawley rats were administered a single equimolar dose (70 mM) of CGS (21 mg/kg), CIS (24 mg/kg), CdTe (17 mg/kg), or saline by intratracheal instillation. Bronchoalveolar lavage fluid (BALF) protein, fibronectin, inflammatory cells, lung hydroxyproline, and tissue distribution were measured 1, 3, 7, 14, and 28 days after instillation. Relative lung weights were significantly increased in CIS- and CdTe-treated rats at most time points. Inflammatory lesions in the lungs consisting of an influx of macrophages, lymphocytes, and PMNs were most severe in CdTe-treated rats, intermediate in CIS-treated rats, and minimal in rats receiving CGS. Hyperplasia of alveolar type 2 cells was present in CIS- and CdTe-treated rats and was greatest in CdTe-treated rats. Pulmonary interstitial fibrosis was observed in CdTe-treated rats at all time points. All three compounds caused marked increases in total BALF cell numbers, with the greatest increase observed in CIS-treated rats. BALF protein, fibronectin, and lung hydroxyproline were significantly increased in all treated animals and were highest in CdTe-treated animals. There was no apparent pulmonary absorption or tissue distribution of CGS. Indium levels increased in extrapulmonary tissues of CIS-treated rats, although Cu and Se levels remained unchanged. CdTe was absorbed from the lung to a greater extent than CGS and CIS. Cd and Te levels decreased in the lung and increased in extrapulmonary tissues. Of these compounds CdTe presents the greatest potential health risk because it causes severe pulmonary inflammation and fibrosis and because it is readily absorbed from the lung may potentially cause extrapulmonary toxicity.     

Clinical and genetic analysis of a pedigree of a thirty-six-year-old familial Alzheimer''s disease patient

Distribution of apolipoprotein(apo) E4 and E3 in lipoproteins of serum with apoE4/E3 phenotype was analyzed. ApoE was eluted in two major peaks by gel chromatography; peak 1 and 2 corresponding to very- and intermediate-low density lipoprotein (VLDL + IDL) and high density lipoprotein2 (HDL2), respectively. ApoE in peak 1 (VLDL + IDL) consisted of monomers of 34 kDa, complexes with a high molecular weight (apoEs) of 100 kDa and with a small amount of apoE-AII complexes weighing 43 kDa. In contrast, apoE in peak 2 (HDL2) was composed mainly of apoE-AII complexes and apoEs complexes, and a small amount of monomers. Both apoE3 and E4 isoforms were detected in these peaks; E4 was more predominant in peak 1 while E3 was more predominant in peak 2. These findings suggest that different distributions of apoE3 and E4 in lipoprotein particles.     

Elective delivery of infants with macrosomia in diabetic women: reduced shoulder dystocia versus increased cesarean deliveries

OBJECTIVE: We sought to test the hypothesis that elective delivery of infants diagnosed with macrosomia by ultrasonographic studies in diabetic women will significantly reduce the rate of shoulder dystocia without significantly increasing cesarean section rate. STUDY DESIGN: In a prospective study diabetic women with ultrasonographic estimated fetal weight > or = 4250 gm underwent elective cesarean section; women with estimated fetal weight > or = 90th percentile but < 4250 gm underwent induction of labor. Maternal and neonatal outcomes were analyzed and compared for the periods before and after initiation of the protocol. RESULTS: A total of 2604 diabetic patients were included in this study. The rate of shoulder dystocia was significantly lower after instituting the protocol (2.4% vs 1.1%, odds ratio 2.2). The cesarean section rate increased significantly between the two periods (21.7% vs 25.1%, p < 0.04). Ultrasonography correctly identified the presence or absence of macrosomia in 87% of patients. Only 10.6% of diabetic patients at term required intervention under the protocol (6.8% labor induction, 3.8% elective cesarean section). The rate of shoulder dystocia was 7.4% in macrosomic infants delivered vaginally. CONCLUSION: An ultrasonographically estimated weight threshold as an indication for elective delivery in diabetic women reduces the rate of shoulder dystocia without a clinically meaningful increase in cesarean section rate. This practice, in conjunction with an intensified management approach to diabetes, improves the outcome of these high-risk women and their infants.     

Regulation of water and sodium balance in the field by Australian honeyeaters (Aves: Meliphagidae)

We evaluated the use of water and sodium by free-living individuals of several species of Australian honeyeaters (Acanthorhynchos superciliosus, Phylidonyris novaehollandiae, Phylidonyris nigra, Manorina flavigula, and Anthochaera carunculata). Water and Na fluxes were highly variable between species, largely reflecting differences in diet. Water fluxes ranged from approximately 300% of total body water per day in 10-g, nectarivorous A. superciliosus to approximately 45% of total body water per day, typical of a desert species, in M. flavigula, a 50-g, insectivorous, arid-zone bird. Similarly, Na fluxes ranged from nearly 60% of Na pool per day in A. superciliosus to about 25% per day in M. flavigula. Despite these different fluxes, values of regulated osmoregulatory variables, including plasma osmolality, hematocrit, plasma concentrations of Na+ and K+, and exchangeable Na pool, were relatively invariant both between species and within species at different seasons. In contrast, values of variables reflecting the operation of regulatory systems did differ between species and seasons. Urine concentrations were highest in M. flavigula and, in A. carunculata, varied seasonally (higher in summer than winter). Plasma concentrations of aldosterone were lowest in A. carunculata (5-25 pg/mL), highest in P. novaehollandiae (70-200 pg/mL), and in the latter species were higher in winter than summer. Concentrations of arginine vasotocin ranged from 5 pg/mL in A. carunculata to greater than 30 pg/mL in M. flavigula. Our data demonstrate that within the family Meliphagidae, there exists substantial variation in the fluxes of water and Na and that these relate in part to body size variation but more importantly to diet. The different fluxes between species are reflected in the values of numerous osmoregulatory variables.     

Vascular and cardiac effects of amlodipine in acute heart failure in dogs

BACKGROUND: Amlodipine improves exercise capacity in patients with chronic congestive heart failure (HF), but the mechanisms of this effect are unknown. OBJECTIVE: To test the hypothesis, in a canine model of acute, ischemic HF, that amlodipine increases vascular capacitance and reduces cardiac filling pressures. METHODS: Amlodipine was given to 13 anesthetized, splenectomized dogs (six controls and seven with HF). Aortic, left ventricular end-diastolic (LVEDP) and portal venous (Pportal) pressures, cardiac output, portal flow (ultrasonic probe) and intestinal blood volume (IBV, 99mTc blood-pool scintigraphy) were measured. Intestinal vascular conductance (= 1/resistance) and vascular capacitance (CAP) were measured before and 15 mins after repetitive 150 micrograms/kg dosages of amlodipine (maximum cumulative dosage, 1000 micrograms/kg). Pportal-IBV curves were obtained by impeding portal flow (pneumatic cuff), and change in CAP was defined by the change in IBV at Pportal = 7.5 mmHg. HF was induced by microsphere embolization of the left coronary artery. RESULTS: CAP increased in the control group (+ 28%, P < 0.01) but decreased (-9%, P < 0.05) in the HF group. Left ventricular stroke work increased in the control group (P < 0.05), while it decreased (P < 0.05) in the HF group, suggesting a negative inotropic effect. In the control group, LVEDP increased after amlodipine was given (P < 0.05) but did not change significantly in the HF group. CONCLUSIONS: In the acute experimental HF model, amlodipine failed to increase intestinal vascular CAP or decrease filling pressures, and may have had a negative inotropic effect. The experiment failed to demonstrate a beneficial hemodynamic effect of amlodipine in acute HF, and the mechanism of benefit of this agent in chronic HF remains unclear.     

Reduced ratio of male to female births in several industrial countries: a sentinel health indicator?

CONTEXT: The sex ratio of 1.06:1, the ratio of male to female births, has declined over the past decades. Recent reports from a number of industrialized countries indicate that the proportion of males born has significantly decreased, while some male reproductive tract disorders have increased. OBJECTIVES: To examine the evidence for declines in the male proportion at birth and suspected causes for this decline, and to determine whether altered sex ratio can be considered a sentinel health event. DATA SOURCES: Birth records were analyzed from national statistical agencies. STUDY SELECTION: Published analyses of trends in ratio of males to females at birth and studies of sex determinants evaluating epidemiological and endocrinological factors. DATA EXTRACTION: Proportion of males born: 1950-1994 in Denmark; 1950-1994 in the Netherlands; 1970-1990 in Canada; and 1970-1990 in the United States. DATA SYNTHESIS: Since 1950, significant declines in the proportion of males born have been reported in Denmark and the Netherlands. Similar declines have been reported for Canada and the United States since 1970 and parallel declines also have occurred in Sweden, Germany, Norway, and Finland. In Denmark, the proportion of males declined from 0.515 in 1950 to 0.513 in 1994. In the Netherlands, the proportion of males declined from 0.516 in 1950 to 0.513 in 1994. Similar declines in the proportion of males born in Canada and the United States are equivalent to a shift from male to female births of 8600 and 38000 births, respectively. Known and hypothesized risk factors for reduced sex ratio at birth cannot fully account for recent trends. CONCLUSION: Patterns of reduced sex ratio need to be carefully assessed to determine whether they are occurring more generally, whether temporal or spatial variations are evident, and whether they constitute a sentinel health event.     

Retrieval dynamics in recognition and list discrimination: further evidence of separate processes of familiarity and recall

Two experiments tested the hypothesis that the time course of retrieval from memory is different for familiarity and recall. The response-signal method was used to compare memory retrieval dynamics in yes-no recognition memory, as a measure of familiarity, with those of list discrimination, as a measure of contextual recall. Responses were always made with regard to membership in two previous study lists. In Experiment 1 an exclusion task requiring positive responses to words from one list and negative responses to new words and words from the nontarget list was used. In Experiment 2, recognition and list discrimination were separate tasks. Retrieval curves from both experiments were consistent, showing that the minimal retrieval time for recognition was about 100 msec faster than that for list discrimination. Repetition affected asymptotic performance but had no reliable effects on retrieval dynamics in either the recognition or the list-discrimination task.