Prolonged Adverse Effects of Benzalkonium Chloride and Sodium Dodecyl Sulfate in a Primary Culture System of Rabbit Corneal Epithelial Cells

This investigation was undertaken to determine prolonged adverseeffects of benzalkonium chloride (BzCl), a cationic surfactant,and sodium dodecyl sulfate (SDS), an anionic surfactant, afteran initial treatment of and subsequent removal from a primaryculture system of rabbit corneal epithelial cells. Metabolicintegrity and cell growth were evaluated at specified periodsafter a 1-hr treatment with the surfactants because of theirimportance in tissue repair. Intracellular calcium ([Ca²⁺]₁)and intracellular pH (pH₁) were also measured because of theirimportance in cellular homeostasis. ATP/ADP ratios were usedto assess metabolic integrity, and propidium iodide stainingof cells was used to measure relative cell number and cell growth.Digitized fluorescence imaging was used to measure [Ca²⁺]₁ withfura-PE3 and pH₁ with 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein(BCECF). BzCl induced a concentration-dependent decrease inATP/ADP ratios 24 hr after its removal from the cultures, whereasSDS had minimal effects on metabolic integrity throughout the48-hr postexposure measurement period. The proliferative responseof cultures treated with SDS, however, was decreased when comparedwith BzCl-treated cells. BzCl induced an increase in [Ca²⁺]₁,whereas SDS decreased [Ca²⁺]₁ 1–3 hr after removal ofsurfactants. BzCl produced a sustained decrease in pH₁ in survivingcells 1–4 hr after its removal, with a return to controlvalues at 24–48 hr. SDS transiently increased pH₁ 1 hrafter its removal and decreased pH₁ at the 48-hr post-treatmentperiod. In conclusion, the two surfactants in vitro had distinctlydifferent prolonged effects on corneal epithelial cells, whichmay suggest that BzCl and SDS differentially affect cellularrecovery in vivo.     

Oral Toxicity of Carbon Tetrachioride: Acute, Subacute, and Subchronic Studies in Rats

Oral Toxicity of Carbon Tetrachloide: Acute, Subacute, and SubchronicStudies in Rats. BRUCKNER, J. V., MACKENZIE, W. F., MURALIDHARA,S., LUTHRA, R., KYLE, G. M., AND ACOSTA, D. (1986). Fundam.Appl. Toxicol. 6, 16–34. This investigation was conductedto characterize the acute, subacute, and subchronic toxic potencyof ingested carbon tetrachloride (CCl₄) In the first acute andsubacute toxicity study, male Sprague-Dawley rats of 300–350g were gavaged with 0, 20, 40, or 80 mg CCl₄/kg once daily for5 consecutive days, rested for 2 days, and dosed once dailyfor 4 additional days. Rats of 200–250 g were gavagedwith 0, 20, 80, or 160 mg CCl₄/kg according to the same dosageregimen in the second acute and subacute study. In the firstand second studies one group of rats at each dosage level wassacrificed for clinical chemistry and histopathological evaluationat 24 hr, 4 days, and 11 days after initiation of dosing. Single20- and 40-mg/kg doses had no apparent toxic effect at 24 hr,although 80 mg/kg caused mild hepatic centrilobular vacuolizationand significant increases in some serum enzyme levels. In general,there was progressively severe hepatic injury at each dosagelevel over the 11-day period. CCl₄ was more hepatotoxic to the200–250-g rats than to the 300–350-g rats. In thesubchronic study, rats initially 200–250 g were gavaged5 times weekly for 12 weeks with 0, 1, 10, or 33 mg CCl4/kgBody weight and clinical chemistry indices were monitored duringthe 12 weeks of dosing and 2 weeks after cessation of dosing,A dose of 1 mg/kg had no apparent adverse effect; 10 mg/kg producedslight, but statistically significant increases in sorbitoldehydrogenase activity and mild hepatic centrilobular vacuolization;33 mg/kg caused marked hepatotoxicity. Serum enzyme levels remainedelevated during the 12-week dosing period, but returned towardnormal within 13 days of cessation of CCl₄ exposure. Microscopicexamination of livers of the 33-mg/kg rats revealed cirrhosis,characterized by bile duct proliferation, fibrosis, lobulardistortion, parenchymal regeneration, hyperplastic nodules,and single-cell necrosis. The fibrosis was not reversed withinthe 13-day recovery period.     

Identification of pemphigus-like antigens expressed by SCaBER cells

Indirect immunofluorescence revealed the presence of pemphigus-like antigenic activity on SCaBER cell monolayers after incubation with sera from patients with pemphigus vulgaris. In contrast, no fluorescence was observed after incubation of the cells with sera from patients with bullous pemphigoid, systemic lupus erythematosus or healthy individuals. In order to identify this pemphigus-like antigen, the SCaBER cell membrane proteins were solubilized in non-ionic detergent, separated according to their molecular weight by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and electrophoretically transferred to nitrocellulose sheets. After incubation with pemphigus serum followed by 125I-radiolabelled goat anti-human IgG, autoradiography revealed pemphigus antibody binding activity in the 105 Kd region in electrophoretograms of the unreduced SCaBER cell membrane extracts. This pemphigus-like antigen was isolated by affinity chromatography on the Sepharose-linked IgG fraction of sera from patients with pemphigus vulgaris.     

Cardiomyoplasty Benefits in Experimental Myocardial Dysfunction

Beneficial effects of cardiomyoplasty have been documented and the use of this technique in the treatment of dilated cardiomyopathy have been suggested. This study was undertaken to evaluate the effectiveness of stimulated preconditioned latissimus dorsi muscle flaps wrapped around the heart in order to restore ventricular contractility in six adult mongrel dogs with induced myocardial dysfunction by administration of beta blockers and volume loading. Hemodynamic and two-dimensional echocardiographic evaluation were performed 1 week after the surgical procedure and immediately after heart failure induction. With synchronous pulse train electrical stimulation, cardiac output increased from 1.46 +/- 0.13 (+/- SD) to 2.01 +/- 0.16 L/min (p less than 0.01), pulmonary wedge pressure decreased from 15.5 +/- 1.2 to 11.3 +/- 1.6 mmHg (p less than 0.01) and left ventricular end-diastolic pressure from 18.3 +/- 2.4 to 13.5 +/- 1.4 mmHg (p less than 0.04). Echo derived left ventricular ejection fraction increased from 39.3 +/- 2.4 to 59.6 +/- 2.9% (p less than 0.01) and segmental wall shortening from 15.4 +/- 1.2 to 26.3 +/- 1.7% (p less than 0.01), inclusive when the muscle flap was wrapped only around the left ventricle. In conclusion, this study suggests that cardiomyoplasty may be an alternative method of treatment for irreversible cardiomyopathy, including in patients with a great cardiac enlargement in which muscle flap may only be wrapped partially around the heart.     

Effect of oral ZnDTPA on late effects of injected plutonium in rat

Purpose: To reduce the long-term toxicity of 239Pu in rats by lifetime drinking of ZnDTPA solution and to investigate possible side-effects of the drug. Materials and methods: Male Sprague-Dawley rats received a single injection of 239Pu citrate, alone or plus oral ZnDTPA. Additional groups were administered only ZnDTPA. Late tissue changes were evaluated by post-mortem examination, X-rays and histologically. Results: The incidence of rat bearing osteosarcoma decreased after treatment to 35% as compared with 53% in untreated controls. The proportional incidence of osteosarcomas was reduced after ZnDTPA by more than the corresponding removal of 239Pu. Unexpectedly in the male rat, mammary tumours, mostly malignant, developed in 20% of rats that received 239Pu as compared with 0.5% in the untreated controls. After a lifetime drinking solely 3x10-3 m ZnDTPA the incidence of diffuse glomerulosclerosis reached 29% as compared with 10% in controls. Conclusions: In rat, protracted oral administration of ZnDTPA reduced the incidence of osteosarcomas after injection of 239Pu, even if treatment started with a delay of 1 month. In the latter case, however, more soft tissue damage was found than after treatment beginning at 4 days post-239Pu. An increased incidence of diffuse glomerulosclerosis was observed as a side effect of oral ZnDTPA only when given continuously, alone and in high amounts.