The Perfect and Famous Anesthetic Known as Methyl in Boston in 1895.

Extravagant claims were made for proprietary dental anesthetics in Boston, MA, in the late 1800s. For instance, in 1883, Urial K. Mayo introduced an inhaled Vegetable Anaesthetic comprised of nitrous oxide that had been uselessly pretreated with botanical material. This misguided concept may have been inspired by homeopathy, but it was also in line with the earlier false belief of Elton R. Smilie, Charles T. Jackson, and William T.G. Morton that sulfuric ether could volatilize opium at room temperature. In 1895, the Dental Methyl Company advertised an agent they called Methyl, a supposedly perfect topical anesthetic for painless dental extraction. The active ingredient was probably chloroform. Anesthetic humbug did not cease in Boston on Ether Day of October 16, 1846.

Studies on effects of Andrographis paniculata (Burm.f.) and Andrographis lineata nees (Family: Acanthaceae) extracts against two mosquitoes Culex quinquefasciatus (Say.) and Aedes aegypti (Linn.).

OBJECTIVE: To investigate the studies on effects of Andrographis paniculata (A. paniculata) (Burm.f.) and Andrographis lineata (A. lineata) nees (Family: Acanthaceae) extracts against two mosquitoes Culex quinquefasciatus (Cx. quinquefasciatus) (Say.) and Aedes aegypti (Ae. aegypti) (Linn.). METHODS: The aqueous and petroleum ether extracts of two plant species, A. paniculata and A. lineate were examined against the larvae of A. aegypti (L.) and Cx. quinquefasciatus with gradually increasing concentration ie. from 50 to 200 ppm of solvent extracts and to test their activity in combination with each other. RESULTS: In a 24 h bioassay experiment with plant extracts, highest mortalities were recorded at 200 ppm of concentrations for leaves of A. lineta and A. paniculata individually. For combination effect, only 150 ppm of the mixture of solvent extracts of petroleum ether: aqueous (1:1) extracts showed 100% mortality after 24 h of exposure. CONCLUSIONS: The results show that, insecticides of plant combination is ecofriend and has better larvicidal activity compared to individual extracts.

Evaluation of antitumour activity of Calotropis gigantea L. root bark against Ehrlich ascites carcinoma in Swiss albino mice.

OBJECTIVE: To investigate experimentally the possible antitumor effect of methanol extract (ME) of Calotropis gigantea L. (C. gigantean) root bark and its petroleum ether (PEF) and chloroform (CF) soluble fractions against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. METHODS: The effects of ME (10 and 20 mg/kg), PEF (40 and 80 mg/kg) and CF (20 and 40 mg/kg) on the growth of EAC and life span of EAC bearing mice were studied. Hematological profile and biochemical parameters (SALP, SGPT and SGOT) were also estimated. RESULTS: Results of in vivo study showed a significant decrease in viable tumor cell count and a significant increase of life span in the ME and CF treated group compared to untreated one. The life span of ME and CF treated animals was significantly (P<0.05) increased by 43.90% (20 mg ME/kg) and 57.07% (40 mg CF/kg). ME and CF brought back the hematological parameter more or less normal level. ME and CF also restored the altered levels of serum alkaline phosphatase (SALP) and serum glutamate oxaloacetate transaminase (SGOT). CONCLUSIONS: Methanol extract (ME) of C. gigantea root bark and its chloroform soluble fraction (CF) possesses significant antitumor activity.

Further studies on the hepatoprotective effects of Anoectochilus formosanus.

The purpose of this study was to investigate the hepatoprotective effects of Anoectochilus formosanus effective fraction (AFEF) on chronic liver damage induced by carbon tetrachloride (CCl4) in mice. CCl4 (5%; 0.1 mL/10 g body weight) was given twice a week for 9 weeks, and mice received AFEF throughout the whole experimental period. Plasma GPT, hepatic levels of hydroxyproline and malondialdehyde were significantly lower in mice treated with AFEF compared with those treated with CCl4 only. Liver pathology in the AFEF-treated mice was also improved. RT-PCR analysis showed that AFEF treatment increased the expression of methionine adenosyltransferase 1A and decreased the expression of collagen(alpha1)(I) and transforming growth factor-beta1. These results clearly demonstrated that AFEF reduced the hepatic damage induced by CCl4 in mice.

Antidyslipidemic activity of Indigofera tinctoria.

Indigofera tinctoria is a perennial shrub, which belongs to the family Papilionaceae. As a part of our drug discovery program we have investigated the antidyslipidemic activity of the alcoholic extract from Indigofera tinctoria as well as its three other components, that is, chloroform, butanol and aqueous fractions in dyslipidemic hamsters that were fed a high fat diet. The chloroform fraction showed a significant decrease in the plasma triglycerides (TG, 52%) (P < 0.001), total cholesterol (TC, 29%) (P < 0.05), glycerol (Gly, 24%) and free fatty acids (FFA, 14%). This decrease was also accompanied by an increase in high density lipoproteins (HDL) by 9% and an increased HDL-C/TC ratio of 52% at the dose of 250 mg/kg of body weight.

Comparative study of different silymarin formulations: formulation, characterisation and in vitro/in vivo evaluation.

The aim of the present study was to study the synergistic hepatoprotective effect of silymarin with phospholipids when it is encaged in microspheres so as to passively target it to liver and to compare these silymarin formulations with silymarin solution. Various silymarin loaded lipid emulsions were formulated which include formulation A prepared with soyabean oil as an internal oily phase, soya lecithin as surfactant and tween 80 as cosurfactant; formulation B which was same as formulation A but was filtered through 0.45 micro membrane filter and finally steam sterilized for intravenous administration; formulation C containing soyabean oil as an internal oily phase, soya lecithin as surfactant, tween 80 and propylene glycol as cosurfactant/ cosolvent. These formulations were compared for their release profile with silymarin solution in propylene glycol, i.e. formulation D. In vivo evaluation was carried out using three models i.e. phenobarbitone induced sleep time in mice, biochemical estimation of SGOT and SGPT enzyme levels and histopathological examination of rat livers. Results revealed that there was significant reduction in sleep time in the mice treated with silymarin loaded lipid microspheres (both p.o. as well as i.v.) when compared with control and even with plain lipid microspheres and silymarin solution and significant reduction in enzyme levels in silymarin lipid microspheres treated group when compared with control, plain lipid microspheres as well as silymarin solution treated group. Histopathological studies also supported the results obtained from the other two models. A positive outcome of these studies gave an insight that if silymarin is coupled with phospholipid in such microparticulate delivery systems, hepatoprotective effect of drug molecules can be pronounced further by self targeting nature and synergistic action.

Efecto de los extractos de cloroformo y tolueno de Cestrum nocturnum L sobre la conducta exploratoria y pruebas de analgesia / Effect of chloroform and toluene extracts of Cestrum nocturnum L on the animal´s exploring behavior and analgesia tests

Se analizó el efecto de la administración aguda de los extractos de cloroformo y tolueno obtenidos a partir de las hojas secas de Cestrum nocturnum L. sobre modelos de conducta exploratoria y pruebas de analgesia El propósito del trabajo fue iniciar la búsqueda de los principios activos relacionados con los efectos sedante y analgésico de la planta. La fracción de cloroformo produjo hipoactividad y redujo la respuesta en la prueba de las contorsiones inducidas por ácido acético de manera dependiente de la dosis sin provocar cambios en el tiempo de reacción en el plato caliente. La fracción de tolueno provocó una disminución de la conducta exploratoria con similar efecto en el tiempo total de permanencia en el círculo central y una disminución de la respuesta al dolor en forma dependiente de las dosis en el modelo de ácido acético. En el plato caliente esta fracción resultó inefectiva. Los resultados sugieren la presencia en ambos extractos de un principio activo con efecto analgésico periférico y otro con acción sedante(AU)

Effect of dosing vehicle on the hepatotoxicity of CCl4 and nephrotoxicity of CHCl3 in rats.

There are conflicting results in the literature concerning the effect of gavage vehicle, corn oil (CO) versus aqueous suspension, on the toxicity of haloalkanes. The purpose of our study was to assess the influence of oral dosing vehicle on the acute hepatotoxicity of CCl4 and nephrotoxicity of CHCl3. Male Sprague-Dawley rats, fed ad libitum, were treated (po) with single doses of CCl4 or CHCl3 using corn oil (CO), or an aqueous preparation (5%) of Emulphor (EL620) or Tween-85 (Tw-85) as vehicle (10 ml/kg). Rats were killed 48 h after treatment. Blood was collected for plasma alanine aminotransferase (ALT) determination and renal cortical slices were prepared for p-aminohippuric acid (PAH) incorporation. The comparison, between gavage vehicles, of the slopes and ED50 of the dose-response curves, although not significantly different, indicated clear trends for enhanced potency with CO for CHCl3 nephrotoxicity but not for CCl4 hepatotoxicity. However, ALT values, a measure of the severity of effect for CCl4, also indicated that CO, when compared to EL620 and Tw-85, tended to enhance CCl4 hepatotoxicity at low toxicity incidence. Furthermore, CO clearly enhanced the severity of effect for CHCl3 nephrotoxicity, as measured by the slice-to-medium PAH ratios, at high dosage. The greater severity of the lesion produced by exposure to these chemicals, when administered in CO, is consistent with the trends observed for their potency (dose-response curves). Our results agree with an increased toxicity of haloalkanes by the gavage vehicle CO reported in the literature. Thus, CO should be considered a potential confounder in hepato- and nephrotoxicity assays.

Chloroform in drinking water prevents hepatic cell proliferation induced by chloroform administered by gavage in corn oil to mice.

Chloroform administered by gavage in corn oil, but not when administrated in drinking water, has been shown to induce liver cancer in female B6C3F1 mice and to enhance cell proliferation. Since humans are exposed to chloroform in their drinking water, we evaluated whether exposure by this route would interact with the activity of chloroform when administered by gavage in corn oil. Female B6C3F1 mice were exposed to chloroform in drinking water for 33 days at 0, 300, or 1800 ppm (Experiment 1) or for 31 days at 0, 120, 240, or 480 ppm (Experiment 2) and for 3 days prior to termination also received a daily dose of 263 mg/kg chloroform administered by gavage in corn oil. Exposure to chloroform in drinking water reduced both the hepatotoxicity and the enhanced cell proliferation (bromodeoxyuridine-labeling index and mitotic index) elicited in response to chloroform administered by gavage in corn oil. Hence, chloroform administered in drinking water reduced the activity of chloroform administered by gavage in corn oil, suggesting that it would also reduce the hepatocarcinogenic activity of chloroform administered by gavage.

Induced regenerative cell proliferation in livers and kidneys of male F-344 rats given chloroform in corn oil by gavage or ad libitum in drinking water.

These studies were designed to establish the dose response relationships for the induction of cytolethality and regenerative cell proliferation in the liver and kidneys of male F-344 rats given chloroform by gavage or in drinking water. Rats were administered oral doses of 0, 10, 34, 90 or 180 mg/kg/day chloroform dissolved in corn oil by gavage for 4 days or for 5 days/week for 3 weeks. A second group of rats was given chloroform ad libitum in the drinking water at concentrations of 0, 60, 200, 400, 900 or 1800 ppm for 4 days or 3 weeks. Bromodeoxyuridine (BrdU) was administered via an implanted osmotic pump 3.5 days prior to necropsy to label cells in S-phase. Cells having incorporated BrdU were visualized in tissue sections immunohistochemically and the labelling index (LI) evaluated as the percentage of S-phase cells. Rats treated with 90 or 180 mg/kg/day by gavage for 4 days had mild to moderate degeneration of renal proximal tubules and centrilobular hepatocytes. These alterations were absent or slight after 3 weeks of treatment. LI were increased in the kidney cortex only in the rats treated with 180 mg/kg/day for 4 days. A dose-dependent increase in LI was seen in rat liver after 4 days of treatment with 90 and 180 mg/kg/day by gavage, but the LI remained elevated after 3 weeks of treatment only at the 180 mg/kg/day dose. When chloroform was administered in the drinking water, no microscopic alterations were seen in the kidneys after 4 days of treatment. As a general observation, rats treated for 3 weeks with 200 ppm chloroform and greater had slightly increased numbers of focal areas of regenerating renal proximal tubular epithelium and cell proliferation than were noted in the controls, but no clear dose response relationship was evident. However, the overall renal LI was not increased at any dose or time point. Similarly, only mild hepatocyte vacuolation was observed in rats given 1800 ppm chloroform in the water for 3 weeks with no increase in the hepatic LI at any time point, even though the rats were consuming chloroform at a rate of 106 mg/kg/day at the 1800 ppm drinking water concentration. These data indicate more severe hepatic and renal toxicity when chloroform is administered by gavage than in the drinking water and a different pattern of regenerative proliferation in the kidney.(ABSTRACT TRUNCATED AT 400 WORDS)

Route of administration determines whether chloroform enhances or inhibits cell proliferation in the liver of B6C3F1 mice.

Chloroform administered by gavage has been shown to induce liver cancer in B6C3F1 mice; however, when administered in the drinking water, chloroform inhibited liver cancer in mice. The effect of chloroform administered by these two routes upon cell proliferation in mouse liver was determined. Female B6C3F1 mice were divided into five treatment groups: (1) chloroform (263 mg/kg body wt) by gavage in corn oil, (2) 1,800 ppm chloroform in drinking water, (3) 1,800 ppm chloroform in drinking water plus 10 ml/kg body wt corn oil by gavage, (4) 10 ml/kg body wt corn oil by gavage, and (5) untreated controls. Five days prior to termination, the mice were implanted subcutaneously with a 7-day osmotic minipump containing 30 mg/ml bromodeoxyuridine. Mice were terminated after 5, 12, 33, and 159 days of exposure. Chloroform administered by gavage in corn oil increased cell proliferation at all terminations, while, when administered in drinking water, cell proliferation was inhibited on Days 5 and 12. At 33 and 159 days, chloroform administered in the drinking water did not affect cell proliferation, even though the dose received by the animals was comparable to that given in corn oil by gavage. Therefore, cell proliferation was enhanced only by chloroform administered in corn oil by gavage, which corresponds to the hepatocarcinogenicity of chloroform administered by this route.

Effects of chloroform and bromodichloromethane on DNA synthesis in male F344 rat kidney.

We have been investigating the actions of chloroform (CHCl3) and bromodichloromethane (BDCM) in rat kidney after different routes of exposure. Male F344 rats were exposed by gavage with corn oil or water as the diluting vehicle. All experiments lasted 30 days with gavage exposures 5 days per week for 4 weeks (20 doses). All animals were injected IP with bromodeoxyuridine (BrdU) 3 times over a 6-day period at 50 mg/kg/injection. Kidney tissue was fixed and slides were stained with hematoxylin and eosin for routine viewing and by the PAP (peroxidase-antiperoxidase) technique using anti-BrdU to label cells in DNA synthesis. There were no significant changes in gross parameters evaluated between the control rats and the rats exposed to CHCl3 or BDCM. Rats exposed via corn oil gavage to CHCl3 displayed a segment-specific epithelial cell necrosis (6/6 high dose, 2/6 low dose). The lesions were primarily localized to the second segment of the proximal tubule, although some spread to cells in the first segment was occasionally observed. No histologic lesions were observed in the kidneys of rats exposed to BDCM. Preliminary results indicate a significant increase in DNA synthesis in the CHCl3-treated rats and a slight increase in DNA synthesis in BDCM-treated rats with corn oil as the diluent. The increase in BrdU labeling was primarily in cells of the S2 segment of the proximal tubule and interstitial cells of CHCl3-exposed animals and in cells of the S3 segment of BDCM-exposed animals.(ABSTRACT TRUNCATED AT 250 WORDS)