Use of hemodialysis after ingestion of a mixture of acids containing hydrofluoric acid.

Hydrofluoric acid (HF) is a highly toxic poison that can be rapidly fatal. Death usually results from the many systemic effects of dissociated fluoride ions, including hypocalcemia, hypomagnesemia, hyperkalemia, and direct cardiotoxicity. A patient is described who accidentally ingested a hydrofluoric acid-containing substance and who likely benefited from hemodialysis. His fluoride level post-dialysis was reduced by approximately 70% from a level drawn three hours prior to the initiation of hemodialysis. However, the single treatment did not reduce the fluoride level to normal. A review of the pathophysiology of hydrofluoric acid intoxication and the outcomes of prior exposures suggests that hemodialysis could play a vital role in the management of poisonings with fluoride-containing substances. However, the initial hemodialysis treatment should be prolonged beyond the standard four-hour session.

Proton order in the ice crystal surface.

The physics of the ice crystal surface and its interaction with adsorbates are not only of fundamental interest but also of considerable importance to terrestrial and planetary chemistry. Yet the atomic-level structure of even the pristine ice surface at low temperature is still far from well understood. This computational study focuses on the pattern of dangling H and dangling O (lone pairs) atoms at the basal ice surface. Dangling atoms serve as binding sites for adsorbates capable of hydrogen- and electrostatic bonding. Extension of the well known orientational disorder ("proton disorder") of bulk crystal ice to the surface would naturally suggest a disordered dangling atom pattern; however, extensive computer simulations employing two different empirical potentials indicate significant free energy preference for a striped phase with alternating rows of dangling H and dangling O atoms, as suggested long ago by Fletcher [Fletcher NH (1992) Philos Mag 66:109-115]. The presence of striped phase domains within the basal surface is consistent with the hitherto unexplained minor fractional peaks in the helium diffraction pattern observed 10 years ago. Compared with the disordered model, the striped model yields improved agreement between computations and experimental ppp-polarized sum frequency generation spectra.

Sum frequency generation surface spectra of ice, water, and acid solution investigated by an exciton model.

A new computational scheme is presented for calculation of sum frequency generation (SFG) spectra, based on the exciton model for OH bonds. The scheme is applied to unified analysis of the SFG spectra in the OH-stretch region of the surfaces of ice, liquid water, and acid solution. A significant role of intermolecularly coupled collective modes is pointed out. SFG intensity amplification observed for acid solutions in the H-bonded OH-stretch region is reproduced qualitatively and accounted for by enhanced orientational preference "into the surface" of the H(2)O bisectors within the hydronium solvation shell.

Naphthalene-induced respiratory tract toxicity: metabolic mechanisms of toxicity.

The lung, which is in intimate contact with the external environment, is exposed to a number of toxicants both by virtue of its large surface area and because it receives 100% of the cardiac output. Lung diseases are a major disease entity in the U.S. population ranking third in terms of morbidity and mortality. Despite the importance of these diseases, key issues remain to be resolved regarding the interactions of chemicals with lung tissue and the factors that are critical determinants of chemical-induced lung injury. The importance of cytochrome P450 monooxygenase dependent metabolism in chemical-induced lung injury in animal models was established over 25 years ago with the furan, 4-ipomeanol. Since then, the significance of biotransformation and the reasons for the high degree of pulmonary selectivity for a myriad of different chemicals has been well documented, mainly in rodent models. However, with many of these chemicals there are substantial differences in the susceptibility of rats vs. mice. Even within the same species, varied levels of the respiratory tract respond differently. Thus, key pieces of data are still missing when evaluating the applicability of data generated in rodents to primates, and as a result of this, there are substantial uncertainties within the regulatory community with regards to assessing the risks to humans for exposure to some of these chemicals. For example, all of the available data suggest that the levels of cytochrome P450 monooxygenases in rodent lungs are 10-100 times greater than those measured in the lungs of nonhuman primates or in man. At first glance, this suggests that a significant margin of safety exists when evaluating the applicability of rodent studies in the human, but the issues are more complex. The intent of this review is to outline some of the work conducted on the site and species selective toxicity and metabolism of the volatile lung toxic aromatic hydrocarbon, naphthalene. We argue that a complete understanding of the cellular and biochemical mechanisms by which this and other lung toxic compounds generate their effects in rodent models with subsequent measurement of these cellular and biochemical events in primate and human tissues in vitro will provide a far better basis for judging whether the results of studies done in rodent models are applicable to humans.

Self-collection of vaginal swabs for the detection of Chlamydia, gonorrhea, and trichomoniasis: opportunity to encourage sexually transmitted disease testing among adolescents.

BACKGROUND: Many sexually transmitted diseases (STDs) are prevalent among adolescents, yet compliance to undergo STD testing by this population is suboptimal. Efforts to enhance compliance with testing among at-risk youth are needed. GOAL: To determine the feasibility and acceptability of self-collection of vaginal swabs for the detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis among high-school students attending a school health clinic. STUDY DESIGN: Enrolled in the study were 228 female students between the ages of 15 and 19 years. Each student self-collected a single vaginal swab that was tested for C trachomatis, N gonorrhoeae, and T vaginalis by polymerase chain reaction amplification. Acceptability of self-collection of vaginal swabs was assessed. RESULTS: The prevalence of any STD was 18%. Trichomoniasis, chlamydia, and gonorrhea were diagnosed in 10%, 8%, and 2% of students, respectively. Nearly 13% of females who had never previously had a gynecologic examination tested positive for an STD, and 51% of infected students would not have pursued testing by traditional gynecologic examination if self-collection was not offered. Self-collection of vaginal swabs was almost uniformly reported as easy to perform (99%) and preferable to a gynecologic examination (84%). Nearly all (97%) stated that they would undergo testing at frequent intervals if self-testing were available. CONCLUSIONS: Self-collected vaginal swabs for STD testing can be easily implemented in a high-school setting with high acceptability among students, enabling the detection of many STDs that would otherwise remain undetected and untreated.

Metabolic capabilities of CYP2F2 with various pulmonary toxicants and its relative abundance in mouse lung subcompartments.

The tissue- and species-selective toxicity of a number of pulmonary toxicants has been attributed to the presence and distribution of activating enzymes with high k(cat) in target airways of susceptible species. The mouse is especially sensitive to a variety of metabolically activated lung toxicants. Recombinant CYP2F2 (mouse) was recently shown to effectively metabolize the species-selective pulmonary toxicant naphthalene. Here we show that the pulmonary toxicants 1-nitronaphthalene and 2-methylnaphthalene are metabolized readily with high k(cat) values (17.1 and 67.6 min(-1), respectively) to potentially cytotoxic intermediates at biologically relevant K(m) values (21.5 and 3.7 microM, respectively). Additionally, anthracene and benzo[a]pyrene are both metabolized by CYP2F2 (0.14 +/- 0.04 and 0.04 +/- 0.00 nmol/nmol/min, respectively), albeit at much lower rates. The levels of total CYP in mouse airways are considerably higher than those in parenchyma and trachea, and this is consistent with much higher rates of naphthalene metabolism in microsomal preparations from airways compared with the other subcompartments. The data suggest that CYP2F2 is a prominent cytochrome P450 in mouse lung that metabolizes a number of pulmonary toxicants. The presence of CYP2F2 may be important in the susceptibility of the mouse to metabolically activated pulmonary toxicants.

Intraocular lens power calculations in patients with extreme myopia.

PURPOSE: To determine the variables that might contribute to improved intraocular lens (IOL) power calculations preoperatively in cataract patients with extreme myopia. METHODS: This retrospective study included 50 patients with extreme myopia and axial lengths longer than 27.0 mm. All patients had clear corneal phacoemulsification by the same surgeon and implantation of the Domilens SiFlex 1 IOL (power range -6.0 to +5.0 diopters [D]). The performances of the SRK/T, Hoffer Q, Holladay 1, and Holladay 2 formulas in predicting an IOL power that would meet the target refraction of +/-1.00 D were compared. RESULTS: The formulas tended to suggest underpowered IOLs, more severe in eyes with axial lengths greater than 30.00 mm. These eyes accounted for most of the minus-power IOLs implanted. Back calculations of axial lengths in patients with minus-power IOLs showed that, on average, emmetropia could have been predicted by choosing shorter axial lengths (up to 2.72 mm shorter) than those used in the original IOL power calculations. Preoperative B-scan ultrasonography demonstrated the presence of a posterior pole staphyloma temporal to the optic nerve in several patients who required minus-power IOLs, which suggests that axial length measurement problems were a major source of IOL calculation errors in these patients. CONCLUSIONS: In eyes with axial lengths longer than or equal to 27.0 mm, current third- and fourth-generation lens calculation formulas have a tendency to over minus patients between -1.0 and -4.0 D. The formulas appear to perform better for plus-power IOL implantation than for minus-power IOL implantation. The use of B-scan ultrasonography to locate posterior pole staphylomas may improve the accuracy of IOL calculations in eyes with extreme myopia.

Probing the role of interfacial residues in a dimerization inhibitor of HIV-1 protease.

The importance of each side chain of a cross-linked interfacial peptide inhibitor of HIV-1 protease was evaluated using an alanine scanning approach. Whereas the parent inhibitor has an IC50 value of 350 nM, values for the mutations reported here range from 280-9200 nM. The relative importance or each residue was thus assigned and correlated to the solvent accessible surface area (SASA) exposed upon mutation.

Role of murine cytochrome P-450 2F2 in metabolic activation of naphthalene and metabolism of other xenobiotics.

Despite their substantially lower levels relative to hepatic tissue, pulmonary cytochrome P-450 (CYP) monooxygenases play an important role in the metabolic activation of substrates that cause lung injury. The target- and species-selective toxicity of a number of pulmonary toxicants has been attributed to the presence and distribution of activating enzymes with high kcat in target airways of susceptible species. However, experimental demonstration of these concepts and quantitative assessment of the contribution of individual CYP isoforms is lacking. This study was undertaken to characterize the catalytic activities of CYP2F2 with naphthalene, a murine Clara cell toxicant, as well as with other xenobiotics that either undergo metabolic activation to cytotoxic intermediates or that function as "isoform-selective" substrates. Recombinant CYP2F2 was produced using the baculovirus expression vector system in Spodoptera frugiperda and Trichoplusia ni cells, accounting up to approximately 20% of the total cellular protein. Incubations containing naphthalene, recombinant CYP2F2, NADPH-cytochrome P-450 oxidoreductase, and NADPH-regenerating system metabolized naphthalene with a high degree of stereoselectivity to 1R, 2S-naphthalene oxide (66:1 enantiomeric ratio). The Km and kcat values, along with the specificity constant, for naphthalene metabolism by recombinant CYP2F2 were 3 microM, 104 min-1, and 5.8 x 10(5) M-1 s-1, respectively. Recombinant CYP2F2 also metabolized ethoxyresorufin, pentoxyresorufin, p-nitrophenol, and 1-nitronaphthalene at easily detectable levels. The results from this work suggest that CYP2F2 1) plays a key role in the species- and cell-selective toxicity of naphthalene and 2) efficiently metabolizes a number of other substrates, including the lung toxicant 1-nitronaphthalene.

Laser in situ keratomileusis for low myopia and astigmatism with a scanning spot excimer laser.

PURPOSE: To determine the efficacy, predictability, safety, and short term stability of laser in situ keratomileusis (LASIK) in treating patients with low myopia and astigmatism using the Chiron Technolas Keracor 117 PlanoScan excimer laser. METHODS: We retrospectively studied the results of our initial 83 eyes with myopia ranging from -1.13 to -7.25 diopters (D) and astigmatism of no more than 4.00 D that underwent LASIK with the Chiron Technolas Keracor 117 PlanoScan. Follow-up was at 1 day, 1 month, and 3 to 6 months. RESULTS: Mean baseline spherical equivalent refraction was -3.54 +/- 1.41 D and cylinder -1.64 +/- 1.14 D. Mean postoperative spherical equivalent refraction was -0.52 +/- 0.50 D at 1 month and -0.65 +/- 0.62 D at 3 to 6 months; mean postoperative refractive cylinder was -0.45 +/- 0.54 D at 1 month and -0.50 +/- 0.63 D at 3 to 6 months. Fifty-three percent (44 eyes) achieved a spherical equivalent refraction within +/- 0.50 D and 81% (67 eyes) within +/- 1.00 D of emmetropia at the last examination. Fifty-seven percent (47 eyes) achieved a refractive cylinder of < or = 0.50 D, and 27% (22 eyes) had an undercorrection of their refractive cylinder at the last examination. An uncorrected visual acuity of 20/40 or better was achieved in 86% (71 eyes) of patients on postoperative day one, in 81% (67 eyes) at 1 month, and in 76% (63 eyes) at 3 to 6 months. Twenty-eight percent (23 eyes) saw 20/20 or better uncorrected at the last visit (41% [34 eyes] had a baseline spectacle-corrected visual acuity of 20/20). There was no statistically significant difference in the refractions or uncorrected visual acuities between the different postoperative examinations. No eye experienced a loss of spectacle-corrected visual acuity of more than one line at the last examination. CONCLUSION: LASIK with the Chiron PlanoScan excimer laser appears to be an effective, safe, and reasonably predictable means to reduce low myopia and astigmatism. Adjustment of computer algorithms is needed to decrease the number of under-corrections.

Inhibition of cellobiohydrolase I from Trichoderma reesei by palladium.

Cellulase from Trichoderma reesei is a multienzyme mixture that hydrolyzes cellulose to glucose. Two enzymes in this mixture, cellobiohydrolase (CBH) and endoglucanase (EG), possess a common structure comprising a distinct cellulose-binding domain (CBD) and catalytic domain. Inhibition of the catalytic domain of cellulases without affecting their CBD function might be useful for structure/function studies of these enzymes. Complexes of the platinum group metals were tested for their ability to inhibit the major cellulase enzyme from T. reesei, cellobiohydrolase I (CBH I). Only palladium complexes inhibited CBH I, inhibition being dependent upon the molar ratio of palladium to CBH I with 1 microM CBH I retaining only 10% of its activity in the presence of 100 microM ammonium hexachloropalladate(IV) and after the incorporation of 28 mol Pd/mol CBH I. Inhibition was irreversible and could be completely prevented by including histidine, cysteine, and cystine in the assay mixture. Although the primary mechanism of inhibition of CBH I by palladium remains to be elucidated, it could involve the binding of palladium to sulfur or cystine residues resulting in their degradation. This is based on the findings that (i) palladium-inhibited CBH I was less thermally stable than native CBH I; (ii) CBH I, chemically modified by the attachment of pentaammine ruthenium(III) to the imidazole-N of either H206 or H228, showed greater sensitivity to inhibition by palladium compared to native CBH I; and (iii) ammonium hexachloropalladate cleaved 5,5'-dithiobis(2-nitrobenzoic acid)--Ellman's reagent. Binding of CBH I to crystalline cotton linters was not affected by palladium.

Palladium--a new inhibitor of cellulase activities.

Palladium complexes have been shown to strongly inhibit cellobiohydrolase I (CBH I) and endoglucanase II (EG II), two cellulases produced by Trichoderma reesei. Also inhibited were total cellulase (Avicelase) and beta-glucosidase (cellobiase) activities. The catalytic domain of CBH II, the second most abundant component of this cellulase, appeared less susceptible to inhibition by palladium. The inhibition was irreversible and could be prevented if histidine, cysteine or cystine was added to the enzyme reaction mixture simultaneously with the inhibitor. The binding of CBH I to microcrystalline cellulose (Avicel) was unaffected by palladium.