Comparative Absorption of Lead from Contaminated Soil and Lead Salts by Weanling Fischer 344 Rats

A 44-day dosed feed study was performed to compare the bioavailabilityof lead from contaminated soil versus two lead salts and theeffect of soil on gastrointestinal absorption of ingested lead.Male Fischer rats (approximately 4 weeks of age) received lead,17, 42, or 127 ppm, in the form of lead acetate, lead sulfide,lead-contaminated soil, or combinations thereof in the dietfor 7, 15, or 44 days. Control soil was added to the diets ofsome animals to determine how it might alter lead bioavailability.Blood -aminolevulinic acid dehydratase (-ALAD) and blood, bone,kidney, and liver lead were determined in groups of animalsat each time-point. Blood -ALAD was inhibited in a dose-dependentmanner and to the greatest degree in the lead acetate and leadacetate/control soil groups, followed by the lead sulfide andleadcontaminated soil groups. Bone and tissue lead levels increasedin a dose-dependent manner and were greatest in animals receivinglead acetate and significantly less in animals receiving leadsulfide and lead-contaminated soil. Blood lead levels were generallygreatest by 7 days and stabilized at lower levels thereafter.Bone lead concentration—time patterns did not demonstratethe biphasic change seen with tissues and continued to increasein most treatment groups through the course of the study. Thepresence of soil in the diet clearly attenuated the absorptionof lead acetate, but had little effect on the absorption oflead sulfide. Results of these studies confirm previous observationsthat lead absorption is highly dependent on the form of leadingested and the matrix in which it is ingested. More important,these studies demonstrate that lead in soil may be significantlyless available than estimated by current default assumptionsand that the presence of soil may decrease the availabilityof lead from lead salts on which the default assumptions arebased. Results presented here also demonstrate that the weanlingrat may represent an appropriate model that could be used toobtain relatively rapid and economical estimates of the availabilityof lead in complex matrices such as soil.     

The Chronic Toxicity and Oncogenicity of Inhaled Technical-Grade 1,3-Dichloropropene in Rats and Mice

The Chronic Toxicity and Oncogenicity of Inhaled Technical-Grade1,3-Dichloropropene in Rats and Mice. LOMAX, L, G., STOTT, W.T., JOHNSON, K. A., CALHOUN, L. L., YANO, B. L., AND QUAST,J. F. (1989). Fundam. Appl. Toxicol. 12, 418–431. Maleand female Fischer 344 rats and B6C3F1 mice were exposed byinhalation to target concentrations of 0, 5, 20, or 60 ppm (0,22.7, 90.8, or 272 mg/m³) technical-grade 1,3-dichloropropene(DCPT) 6 hr/day, 5 days/week, for upto 2 years. Ancillary groupsof rats and mice were exposed for 6- and 12- month periods.Significant treatment-related nonneoplastic changes followingexposure for 2 years were morphological alterations in the nasaltissues of rats exposed to 60 ppm and mice exposed to 20 or60 ppm DCPT. In addition, mice exposed to 20 or 60 ppm had hyperplasiaof the transitional epithelium lining the urinary bladder. Survivalof male and female rats and mice exposed to DCPT was similarto that of the corresponding controls. No statistically increasedtumor incidence was observed in treated rats. The only neoplasticresponse observed in mice was an increased incidence of benignlung tumors (bronchioloalveolar adenomas) in male mice exposedto 60 ppm DCPT (22/50 versus 9/50 in controls).     

Crystal-state structural analysis of two γ-lactam-restricted analogs of Pro-Leu-Gly-NH2

The crystal structures of two analogs of Pro-Leu-Gly-NH, (1), containing a γ-lactam conformational constraint in place of the -Leu-Gly- sequences, are described. The highly biologically active (S,R)-diastere-omer 2a is semi-extended at the C-terminus, with the N-terminal Pro residue in the unusual “C₅” conformation [ψ₁=– 0.8(15)°] stabilized by a (peptide)N-H…N(amino) intramolecular H-bond [the N(3)…N(4) separation is 2.687(11)Å]. Conversely, the N,N′-isopropylidene aminal trihydrate of the (S,S)-diastereomer 2b, compound 3, adopts a β-bend conformation at the C-terminus, as already reported for 1. However, the backbone torsion angles [φ= 57.4(4), ψ₂=– 129.9(3)°; ψ₃= - 92.3(4), ψ₃= 6.4(5)°] lie close to the values expected for the corner residues of an ideal type-II β-bend. A weak intramolecular 4 → 1 H-bond is seen between the Gly carboxyamide anti-NH and Pro C=O groups. In the newly formed 2,2,3,4-tetraalkyl-5-oxo-imidazolidin-1-yl moiety the ψ₁ torsion angle is 12.9(4)° and the intramolecular N(3)…N(4) separation is 2.321(4)Å.     

Impact of Gender, Ethnicity, Meal Component, and Time Interval Between Eating and Reporting on Accuracy of Fourth-Graders’ Self-Reports of School Lunch

Objective To validate fourth-graders’ self-reports of school lunch by comparing their reports to lunch observations, and to determine the impact on accuracy of gender, ethnicity, meal component, and time interval between eating and reporting.Design Students were randomly selected, observed eating lunch, and interviewed the same day, next day, or Monday regarding Friday's lunch. Accuracy of reporting items was determined by tallying matched foods (items reported and observed), phantom foods (items reported but not observed), and omitted foods (items not reported but observed). Accuracy of reporting amount eaten was determined by calculating absolute and arithmetic differences.Subjects Subjects were 260 students: 89 same-day, 148 next-day, and 23 Monday recalls; 59 whites (30 boys) and 201 blacks (103 boys) from four schools.Statistical analyses Rates for matched, phantom, and omitted foods; analysis of variance; Friedman's nonparametric analog of analysis of variance; Student-Newman-Keuls’ post hoc comparisons.Results In regard to reporting items, the respective rates for matched, phantom, and omitted foods were 84%, 5%, and 16% for same-day recalls; 68%, 13%, and 32% for next-day recalls; and 38%, 48%, and 62% for Monday recalls. Rates for omitted and phantom foods were higher for Monday recalls than for next-day recalls, which were higher than for same-day recalls (P<.05 for all). In regard to reporting amounts, analysis by gender, ethnicity, and time interval failed to yield significant main or interaction effects. When children correctly reported items eaten, they were quite accurate in reporting amounts eaten. Omitted food rates were lowest for beverage, followed by entree, and highest for miscellaneous and condiment.Applications Even under the best conditions (ie, reporting within 90 minutes after eating school lunch), children have difficulty accurately reporting what they have eaten. As the time interval between eating and reporting increases, accuracy decreases markedly. Techniques that improve reporting of items eaten should result in improved accuracy of reporting amounts eaten. J Am Diet Assoc. 1997;97:1293-1298.     

Benefits Gained,Benefits Lost: Comparing Baby Boomers to Other Generations in a Longitudinal Cohort Study of Self‐Rated Health

Policy Points

• Despite beliefs that baby boomers are healthier than previous generations, we found no evidence that the health of baby boomers is substantially different from that of the previous or succeeding cohorts.
• The effects of increased education, higher income, and lower smoking rates on improving self-rated health were nearly counterbalanced by the adverse effect of increasing body mass index (BMI).
• Assumptions that baby boomers will require less health care as they age because of better education, more prosperity, and less propensity to smoke may not be realized because of increases in obesity.

Context

Baby boomers are commonly believed to be healthier than the previous generation. Using self-rated health (SRH) as an indicator of health status, this study examines the effects of age, period, and birth cohort on the trajectory of health across 4 generations: World War II (born between 1935 and 1944), older baby boomers (born between 1945 and 1954), younger baby boomers (born between 1955 and 1964), and Generation X (born between 1965 and 1974).

Methods

We analyzed Canada’s longitudinal National Population Health Survey 1994-2010 (n = 8,570 at baseline), using multilevel growth models to estimate the age trajectory of SRH by cohort, accounting for period and incorporating the influence of changes in education, household income, smoking status, and body mass index (BMI) on SRH over time.

Findings

SRH worsened with increasing age in all cohorts. Cohort differences in SRH were modest (p = 0.034), but there was a significant period effect (p = 0.002). We found marked cohort effects for increasing education, income, and BMI, and decreasing smoking from the youngest to the oldest cohorts, which were much reduced (education and smoking) or removed (income and BMI) once period was taken into account. At the population level, multivariable analysis showed the benefits of increasing education and income and declines in smoking on the trajectory of improving SRH were almost counterbalanced by the effects of increasing BMI (obesity).

Conclusions

We found no evidence to support the expectation that baby boomers will age more or less healthily than previous cohorts did. We also found that increasing BMI has likely undermined improvements in health that might have otherwise occurred, with possible implications for the need for health care. Period effects had a more profound effect than birth cohort effects. This suggests that interventions to improve health, such as reducing obesity, can be targeted to the entire, or a major portion of the, population and need not single out particular birth cohorts.     

Conformational analysis of homochiral and heterochiral diprolines as β-turn-forming peptidomimetics: unsubstituted and substituted models

The effect of replacing one of the proline residues in either unsubstituted homochiral or heterochiral diproline segments with either a 2- or a 3-substituted prolyl residue on the allowed conformation of the diproline template has been examined. In heterochiral (l-d ) diprolines, placement of a 2-methyl-d -proline residue in the i+ 2 position and placement of either a cis- or trans-3-methyl-l -proline residue in the i+ 1 position results in substituted diproline peptides that adopt the same type II β-turn conformation as that identified experimentally for the unsubstituted diproline peptides. In contrast, placement of a cis-3-methyl-d -proline residue in the i+ 1 position of a homochiral (d-d ) diproline peptide seems to promote a different conformation than that seen in the unsubstituted case, whereas the trans-3-methyl-d -proline residue seems to provide a stabilizing influence for the predicted type VI'β-turn. The demonstrated ability of certain substituted diproline templates to adopt predictable conformations coupled with the development of asymmetric synthetic routes to both 2- and 3-substituted prolyl residues capable of mimicking a variety of side chains should make these templates useful tools in designing specific turn mimics of biologically active molecules.     

The Non-Uniform Distribution of Albumin in Human and Bovine Cornea

In our previous studies, we noted a non-uniform distribution of protein tracer preferentially entering the anterior stromal lamellae of the cornea from the limbus. Given other differences reported previously between the anterior and posterior lamellae of the cornea, and the number of corneal disorders in which abnormalities are preferentially confined to either the anterior or posterior lamellae, we were prompted to examine the distribution of albumin in normal human and bovine cornea.The distribution of albumin in bovine and human cornea was studied immunohistochemically. Total soluble protein and albumin in the anterior 1/3 and posterior 2/3 of the central, middle and peripheral cornea of bovine eyes was measured biochemically. To aid in interpreting the findings, a theoretical model was developed based upon the combined effects of diffusive and convective transport.Using immunohistochemical methods, in both bovine and human eyes, intense staining of albumin was found in the anterior 1/3 of the corneal stroma. There was a gradual reduction in staining intensity from the limbus to the central cornea in the anterior corneal stroma. Less staining was found in the posterior 2/3 of corneal stroma. Additionally, a greater concentration of soluble protein and albumin was found in the anterior stroma than in the posterior stroma of the bovine eyes by biochemical analyses. The theoretical model demonstrated that this distribution of protein required a difference in excluded volume fraction between the anterior and posterior stroma and was consistent with a convective flux originating at the limbus and passing through the corneal stroma.The soluble proteins of the bovine and human cornea are preferentially concentrated in the anterior cornea and near the limbus. This distribution is likely due to differences in excluded volume fraction between the anterior and posterior stroma and a small convective flux passing through the cornea.     

ELECTRON MICROSCOPIC STUDY OF DERMATITIS HERPETIFORMIS

SUMMARY.— Biopsy specimens from 2 patients with dermatitis herpetiformis have been studied by electron microscopy.
The basal lamina showed considerable alteration. In some regions it was completely absent. Where present it showed breaks, considerable thickening, and increase in electron density; it may or may not be applied to the epidermis.
The cells of the stratum basale showed changes in their basal regions, but the superficial regions appeared normal. Pseudopodium-like processes extended into the dermis. The cytoplasm within these processes had a low electron density and contained few organelles, but glycogen was frequently present both in the processes and elsewhere in the cytoplasm. Half-desmosomes were absent where the basal lamina was lacking, and where it was present they were decreased in number or absent.
The dermis showed little alteration apart from infiltration with leucocytes.     

HISTOLOGIC SPECTRUM OF CUTANEOUS INVOLVEMENT IN PATIENTS WITH MYELOGENOUS LEUKEMIA INCLUDING THE NEUTROPHILIC DERMATOSES

Background. Cutaneous manifestations of myeloid leukemia can be specific or nonspecific. The study was designed to determine the prevalence and histologic appearance of cutaneous lesions in patients with myeloid leukemia and various myeloproliferative disorders. Methods. The histologic changes of cutaneous lesions in 52 patients with myelodysplastic syndrome, polycythemia vera, and myeloid, myelomonocytic, or monocytic leukemia are presented in this study. Results. Two types of cellular infiltrates were identified. In the first group, the most common pattern was a diffuse involvement by the leukemic cells through the entire dermis with preservation of a “grenz zone” in the superficial dermis. Two cases exhibited a Kaposi's sarcoma-like pattern, with prominent slit-like blood-filled spaces lined by myeloblasts against a fibrocellular stroma. The second group of lesions was characterized by dense, neutrophilic dermal infiltrates resembling acute neutrophilic dermatosis (Sweet's syndrome) or pyoderma gangrenosum. In two of these cases, scattered immature blast cells admixed with the mature neutrophilic elements were identified. Conclusions. Awareness of these different morphologic features and application of special stains are of value in the evaluation of suspicious cutaneous infiltrates in patients with myeloid leukemia and various myeloproliferative disorders.     

A study of cutaneous photosensitivity induced by amiodarone

Amiodarone-induced cutaneous photosensitivity was studied in 12 subjects treated with the drug. The action spectrum for the abnormal response to sunlight was shown to be within the range of 335-460 (+/- 30) nm. The clinical features of the photosensitivity response suggested that it was most probably a phototoxic reaction, a conclusion supported by the results of in vitro studies which indicated activity mainly against cell membranes. Of the five in vitro models used, three--namely photohaemolysis, the inhibition of DNA synthesis in PHA stimulated lymphocytes and the killing of mouse peritoneal macrophages--provided unequivocal evidence of the phototoxic potential of both amiodarone and its major metabolite, desethylamiodarone. In each model desethylamiodarone produced a greater effect by a factor of between 2 and 10. In vitro, UV-B wavelengths produced a greater effect than UVA but the difference between the effective wavelengths in vivo and in vitro might be explained by the greater absorption of the shorter wavelength UV-B in the epidermis. Zinc oxide-containing preparations appeared to be the most effective in reducing the cutaneous photosensitivity. It is suggested that the long-term cutaneous pigmentation resulting from oral amiodarone has a significant photosensitivity component.