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Vasorelaxant effects of the chloroformic crude extract of Bupleurum fruticosum L. (Umbelliferae) roots on rat thoracic aorta.

The chloroformic crude extract of roots of Bupleurum fruticosum L. (Umbelliferae) showed a concentration-dependent vasorelaxing effect on aortic rings endothelium-deprived and pre-contracted by norepinephrine (NE). The pharmacological effect was not produced through the stimulation of cyclooxygenase, adenyl cyclase, or guanylyl cyclase, since selective inhibitors did not prevent the extract-induced responses. The incubation of the aortic rings with the chloroformic extract (10(-4) g/ml) produced a depression of the concentration-contractile response curve to NE, in normal conditions, and this effect was more evident in Ca2+-free Tyrode solution, suggesting an action on the intracellular mobilization of Ca2+ ions. Moreover, the vasodilator action of Bupleurum fruticosum extract was resistant to the pre-treatment with nifedipine and to the pre-treatment with cyclopiazonic acid (blocker of Ca2+/ATPase). Finally, the chloroformic extract of Bupleurum fruticosum produced a reduction of the contraction obtained by caffeine, an opener of ryanodine-sensitive receptors, suggesting that the plant could elicit the vasorelaxing response by the blockade of ryanodine-sensitive Ca2+ channels of the sarcoplasmic reticulum.

Animals↗

Biophotonic imaging in HO-1.luc transgenic mice: real-time demonstration of gender-specific chloroform induced renal toxicity.

The metabolism of luciferin in mice transgenic for luciferase (luc) produces light that may be detected trans vivo by an intensified CCD camera (biophotonics). Thus, the generation of transgenic promoter-luciferase animals for genes regulated by specific toxic processes, coupled with real-time evaluation of site-specific gene expression may provide novel, non-invasive biomarkers which are predictive of developing toxicity in vivo. As part of a programme to evaluate the potential of biophotonics for predictive toxicology we have conducted a series of studies in HO-1.luc transgenic mice. Male and female animals were treated with chloroform (200 mg/kg, p.o., daily for 5 days) and imaged 2 and 6 h after dosing. During a 2-day washout period, female animals were treated daily with testosterone prior to repeat administration of chloroform for a further 5 days. Comparison of the in vivo response of the luciferase reporter with markers of toxicity measured ex vivo (differential gene expression of adaptive antioxidant response genes, clinical chemistry and microscopic examination) confirms the gender-specific difference in chloroform renal toxicity in HO-1.luc transgenic mice and its reversal following androgenisation of females and correlates with the expression of the endogenous haem oxygenase-1 (HO-1) gene. These studies demonstrate the capacity of biophotonics for real-time site-specific gene expression, which may be predictive of developing toxicity.

Animals↗

Cytotoxicity evaluation of gutta-percha solvents: Chloroform and GP-Solvent (limonene).

OBJECTIVE: The purpose of this study was to compare the cytotoxicity of 2 gutta-percha solvents, chloroform and GP-Solvent, on cell line L929. STUDY DESIGN: 2 gutta-percha solvents were diluted into the concentrations of 1:100, 1:400, and 1:800. The experiment was done in a 96-well tissue-culture plate. Cell viability of L929 was determined after each gutta-percha solvent was left in contact with MTT solution for 3 hours. RESULTS: Both solvents proved toxic at the same levels of concentrations of 1:100 and 1:400 (P>.05). At the dilution of 1:800 the GP-Solvent seems to be more toxic than the chloroform (P < .05). CONCLUSIONS: Within the limitation of this experiment, GP-Solvent was not less cytotoxic than chloroform to the target cells. Because in clinical procedures we use a higher concentration of solvent to dissolve gutta-percha for retreatment than that used in this study, the overflowing of liquefied gutta-percha, or solvent out of apical foramen, should be a cause for concern.

Animals↗

Aspirin in chloroform as an effective adjuvant in the management of chronic neurogenic pain.

OBJECTIVE: To evaluate the effectiveness of topical application of aspirin in chloroform as an adjuvant in the management of chronic neurogenic pain. DESIGN: Intervention study, nonrandomized before-and-after trial. SETTING: A department of physical medicine and rehabilitation in a tertiary-care university teaching hospital. PARTICIPANTS: Fifteen adults who presented with severe, chronic neurogenic pain in whom, conventional methods of treatment were unsuccessful in alleviating the pain. INTERVENTION: A solution of aspirin (acetyl salicylic acid) in chloroform was applied over the painful areas. MAIN OUTCOME MEASURES: A numerical scale from 0 to 100 was used to measure the severity of pain. RESULTS: Seventy-four percent of patients showed a good response, 13% had fair response, and in 13% there was no response. CONCLUSION: Aspirin in chloroform solution is a simple and effective adjuvant in the management of chronic neurogenic pain.

Adult↗

The effect of dose and vehicle on early tissue damage and regenerative activity after chloroform administration to mice.

The relationship between the acute toxicity of orally-administered chloroform and its long-term tumorigenic potential was studied in male mice of the CFLP outbred Swiss albino mouse strain. A single dose of approximately 18 mg CHCl3/kg had no detectable acute toxic effect on the liver or kidneys and did not stimulate regenerative activity, whereas both toxicity and subsequent tissue regeneration were observed with single doses of about 60 mg/kg or higher. The severity of the toxic effects and regenerative changes was greater when corn oil was used as a vehicle for chloroform than when the vehicle was a toothpaste base. In earlier long-term studies in mice of the same strain, kidney tumours occurred in males given 60 mg/kg/day throughout life but not in mice given 17 mg/kg/day. The tumour response was greater when the 60-mg/kg/day dose was given in an oily vehicle than when it was given in toothpaste. The findings are consistent with the hypothesis that early acute toxic change and subsequent repair are a sine qua non for tumorigenesis in the kidney and liver in response to chloroform.

Animals↗

Reduction of chloroform formation potential of humic acid by sonolysis and ultraviolet irradiation.

This study is concerned with the changes of chloroform formation potential during the reaction of humic acid (HA) and sodium hypochlorite caused by different oxidative pretreatments: ultraviolet (UV) irradiation, ultrasonic (US) irradiation or combined UV-US irradiations. The UV and US decomposition of a reagent HA in water was investigated. The characterization of the oxidized HA sample by UV absorptiometry, synchronous fluorescence spectroscopy and size exclusion chromatography points a synergetic effect of the combined process. The values of the chlorine demand and chloroform formation potential were conventionally determined after a 96 h reaction at neutral pH. It was found that all applied processes decreased the concentration of chloroform but the highest decrease was observed for the UV-US treatment.

Chloroform↗

Formation of chloroform by aqueous chlorination of organic compounds.

Thirty organic compounds were selected to investigate their chloroform formation characteristics during chlorination with sodium hypochlorite at pH-values 7.0 and 8.0. These experiments were conducted under conditions similar to those applied on the chlorination of raw water. The results indicated that the chloroform concentrations occurred by the all tested compounds was in the ppm range. The maximum levels of chloroform (11-13 mg/l) were determined during the reaction of resorcinol and phloroglucinol at pH-value 8.0.

Chlorine Compounds↗

Mutagenicity and amount of chloroform after chlorination of bank filtered lake water.

Chlorinated drinking waters produced from humus-rich waters often have a high content of halogenated organic by-products which increases the mutagenicity of drinking water. With in vitro chlorination experiments we studied the formation of chloroform (CHCl3) and mutagenicity of artificially recharged ground water samples. The water samples where obtained from an artificial ground water plant which infiltrates humus-rich lake water through an esker island. The chlorination experiments showed that bank filtration reduced strongly the formation of chloroform and mutagenicity of chlorinated water. Reduction in the amount of chloroform and mutagenicity in chlorinated waters was strongly associated with the decrease in the total content of organic carbon and with the decrease in molecular weight of organic matter during bank filtration.

Carcinogens↗

Residual toxicity after biodegradation: interactions among benzene, toluene, and chloroform.

A microbial enrichment originating from a pristine aquifer was found to aerobically biodegrade benzene and toluene, but not chloroform. This enrichment culture was used to study changes in pollutant toxicity as affected by biodegradative activity. Two assays for toxicity were used: (1) a 48-h acute toxicity test using the freshwater invertebrate Ceriodaphnia dubia and (2) microbial biodegradation activity as affected by the presence of mixed pollutants. At 20-ppm concentrations, toluene was significantly more toxic (99% mortality) to C. dubia than benzene (48% mortality) or chloroform (40% mortality). Also at 20-ppm concentrations, but before biodegradation, toluene was significantly more toxic (88% mortality) to C. dubia than benzene (33% mortality). After biodegradation of 98% of toluene and benzene, significant residual toxicity still remained in the bacterial supernatant: toluene-degraded supernatant caused 33% mortality in C. dubia and benzene-degraded supernatant caused 24% mortality. In the second toxicity assay, examining the effect of mixed pollutants on biodegradation activity, the presence of benzene slowed the biodegradation of toluene, but chloroform had no effect on either benzene or toluene biodegradation. Results indicate that significant toxicity remain after biodegradation and that halogenated aliphatic hydrocarbons may have little or no effect on aromatic hydrocarbon biodegradation at sites impacted by mixed pollutants.

Animals↗

A reappraisal of Simpson's introduction of chloroform.

OBJECTIVE: To examine the introduction of the use of chloroform in childbirth, assessing the role of Sir James Young Simpson, the various motives for the innovation, and the health and sociological consequences for those involved in childbirth. DESIGN: A review of the attitudes of mothers, midwives, obstetricians and family practitioners, based on contemporary publications and subsequent historical analyses. FINDINGS: The context in which chloroform was introduced was fundamentally important to its widespread acceptance in the UK. The use of this drug carried serious implications for the childbearing woman, as well as the practice and status of those who provided her care. KEY CONCLUSIONS: The implications of the introduction of chloroform in childbirth were short, medium and long term. The changes associated with the acceptance of this drug may bear comparison with those relating to certain, current, pain-control methods.

Analgesia, Obstetrical↗

On the modulation of photoinduced fluorescence enhancement and conformational stability of albumin-bound bilirubin: effect of epsilon-NH(2) groups blocking and chloroform binding.

Photoinduced fluorescence enhancement of bilirubin bound to primary binding site on human serum albumin (HSA) was completely ceased when epsilon-NH(2) groups of its internal lysine residues were covalently blocked by acetylation or succinylation though the pigment bound to these derivatives in a folded conformation akin to that bound to HSA. These photoinduced fluorescence modulations cannot be ascribed to the binding of bilirubin to secondary low affinity sites as the CD spectrum of bilirubin bound to these derivatives showed complete inversion upon addition of chloroform which binds to subdomain IIA in HSA where high affinity bilirubin binding site is located. Presence of chloroform reconciled the photoinduced alterations in the CD spectrum observed in its absence, suggesting that chloroform stabilized the bound ligand against light but the fluorescence properties of bilirubin complexed with acetylated or succinylated derivatives remained unchanged. Guanidination of internal epsilon-NH(2) groups in HSA by O-methylisourea did not alter the spectral properties of the bound ligand. These results suggest that salt linkage(s) existing between epsilon-NH(2) groups of lysine residues in HSA and carboxyl groups of bilirubin, act(s) as a potential barrier during conformational rotation of the bound ligand assisted by photoactivation and their abolishment can alter its dynamics and stereoselectivity, a hitherto unnoticed implication of salt linkage(s) in BR-HSA complex.

Bilirubin↗

Multiple homicides as a result of chloroform poisoning: case report and experimental study.

Two cases (involving five murder victims) of multiple homicide by inhalational chloroform intoxication are reported. In the discussion of the findings the valence of toxicological analyses is underlined with regard to the possibility of forcible external suffocation due to occlusion of the respiratory orifices by means of a chloroform-soaked soft covering. In addition storage experiments were performed at +4, +20 and -20 degrees C with cadaver blood mixed with chloroform. The optimal solution for avoiding volatile losses was stored in glass tubes with ground glass stoppers. In cases of unclear death in which involvement of volatile substances is suspected it is, therefore, advisable to preserve an additional blood sample at -20 degrees C in glass tubes that are only opened for the analysis of volatile substances.

Adolescent↗

All here are agog with the chloroform.

Two letters written by James Y. Simpson are included among a bound collection of 25 of his pamphlets held in the Gordon Craig Collection of the Library of the Royal Australasian College of Surgeons. Both letters are written in pamphlets relating to Simpson's championing of chloroform. The first letter is written in a proof copy of a pamphlet titled Notice of a new anaesthetic agent as a substitute for Sulphuric ether in Surgery and Midwifery. This very rare pamphlet was posted to Dr Fleetwood Churchill, a Dublin obstetrician, on 13 November 1847, 9 days after the 'dining room experiment' in Simpson' s home, when the anaesthetic properties of chloroform were dramatically demonstrated. The second letter is written 10 months later and is also addressed to Dr Fleetwood Churchill. The content of both letters is discussed, as is also the rarity of the proof copies of the first printed document describing the use of chloroform.

Anesthesia, Inhalation↗

Foldamer dynamics expressed via Markov state models. I. Explicit solvent molecular-dynamics simulations in acetonitrile, chloroform, methanol, and water.

In this article, we analyze the folding dynamics of an all-atom model of a polyphenylacetylene (pPA) 12-mer in explicit solvent for four common organic and aqueous solvents: acetonitrile, chloroform, methanol, and water. The solvent quality has a dramatic effect on the time scales in which pPA 12-mers fold. Acetonitrile was found to manifest ideal folding conditions as suggested by optimal folding times on the order of approximately 100-200 ns, depending on temperature. In contrast, chloroform and water were observed to hinder the folding of the pPA 12-mer due to extreme solvation conditions relative to acetonitrile; chloroform denatures the oligomer, whereas water promotes aggregation and traps. The pPA 12-mer in a pure methanol solution folded in approximately 400 ns at 300 K, compared relative to the experimental 12-mer folding time of approximately 160 ns measured in a 1:1 v/v THF/methanol solution. Requisite in drawing the aforementioned conclusions, analysis techniques based on Markov state models are applied to multiple short independent trajectories to extrapolate the long-time scale dynamics of the 12-mer in each respective solvent. We review the theory of Markov chains and derive a method to impose detailed balance on a transition-probability matrix computed from simulation data.

Acetonitriles↗

Plasma chloroform concentrations in swimmers using indoor swimming pools.

This study evaluated swimmers and visitors who were exposed to chloroform (CHCl3) at three indoor swimming pools in Modena, Italy. Chloroform was measured in plasma samples of 127 subjects present at the pools and in 40 nonexposed subjects. The analyses were performed by head-space gas chromatography. Chloroform was present in all samples collected from the 127 subjects who attended the pools (median = 7.5 nmol/l; range = 0.8-25.1 nmol/l). Agonistic swimmers who trained for competitions showed a significantly higher mean value of plasma CHCl3 than nonagonistic swimmers and visitors. Plasma CHCl3 levels were significantly correlated with (a) CHCl3 concentrations in water and in environmental air, (b) the number of swimmers in the pools, and (c) the time spent swimming. Covariance analysis showed that plasma CHCl3 levels also depended on the intensity of the sport activity (total explained variance = 67.4%).

Air Pollutants↗

Penetration of chloroform, trichloroethylene, and tetrachloroethylene through human skin.

In vitro dermal absorption was measured for three volatile organic compounds in dilute aqueous solution through freshly prepared and previously frozen human skin. The permeability coefficients at 26 degrees C for chloroform (0.14 cm/h) and trichloroethylene (0.12 cm/h) were similar but much larger than that for tetrachloroethylene (0.018 cm/h). Storage of the skin at -20 degrees C did not significantly affect the penetration of these chemicals. The dermal absorption of chloroform through freshly prepared human skin was not changed significantly by pretreatment of the skin with commonly used consumer products (moisturizer, baby oil, insect repellent, sunscreen); however, the permeability coefficient was found to increase from 0.071 cm/h at 11 degrees C to 0.19 cm/h at 50 degrees C. These data suggest that exposure estimates for chloroform and other contaminants in water should consider the appropriate exposure scenario to properly assess the dermal dose.

Adolescent↗

Ultrasonic destruction of chloroform and carbon tetrachloride in aqueous solution.

The sonochemical destruction of binary mixtures of chloroform and carbon tetrachloride in aqueous solution at 30 kHz has been studied. The influences of initial concentration, bicarbonate/chloride, and acoustical intensity on the destruction rates have been observed. It was found that the destruction of the two compounds appeared to follow pseudo-first-order reaction kinetics with the current experimental concentration range. The rate constant of chloroform for initial concentration as high as 100.4 mg/L decreased compared to initial concentration 36.13 micrograms/L, when the rate constants of carbon tetrachloride hardly changed. However, their destruction rates increased with increasing acoustical intensity and were independent of addition of bicarbonate or chloride. The resulting yield of ionic product (Cl-) for chloroform was determined.

Carbon Tetrachloride↗