A subtoxic dose of CCl4 is known to destroy liver microsomal cytochrome P-450 and this is widely accepted as the mechanism of CCl4 autoprotection. Circumstantial evidence suggests that while cytochrome P-450 is significantly decreased, this mechanism alone cannot explain the phenomenon of autoprotection. Previous studies have established that hepatocellular regeneration is stimulated as early as 6 hr after the administration of a low dose of CCl4. If the early phase stimulation of hepatocellular regeneration by the protective dose is indeed the mechanism of autoprotection, then ablation of this early phase of tissue healing by colchicine should result in an abolishment of autoprotection. Present studies were conducted to test this conceptual premise. The protection afforded by a low dose of CCl4 (LCCl4, 100 microliter/kg, ip) on the toxic effects of a subsequently administered moderately toxic dose of CCl4 (HCCL4, 2.5 ml/kg, ip) was established in male Sprague-Dawley rats. The protective dose provided 100% protection, whereas only 62.5% survival was observed when the corn oil vehicle was administered instead of the protective dose of LCCl4. Colchicine administration (1 mg/kg, ip in saline) 2 hr prior to the injection of LCCl4 led to a complete loss of autoprotection resulting in 100% mortality in rats given the HCCl4. Earlier studies have established that colchicine selectively suppresses the early phase of hepatocellular regeneration at 6 hr without influencing the second phase at 36-48 hr. The consequence of colchicine antimitosis on the toxicological endpoints of liver injury was evaluated by serum enzyme elevations and by histopathological examination of the liver during a time course of 6, 24, 48, 72, and 96 hr after the administration of HCCl4. In the autoprotection regime, after only a transient and modest elevation of serum alanine and aspartate transaminases, complete recovery occurred by 96 hr. Hepatocellular necrosis was consistently lower compared to all other groups. Colchicine preadministration in the autoprotection regime resulted in significantly greater and progressive elevation of the serum enzymes and a correspondingly commensurate progression of hepatic lesion. Toxic effects of HCCl4 alone were more rapidly and maximally augmented by colchicine preadministration. The role of hepatocellular regeneration in autoprotection was evaluated by 3H-thymidine incorporation in hepatocellular nuclear DNA and by morphometric estimation of mitotic index. While HCCl4 alone resulted in some stimulation of 3H-thymidine incorporation and mitosis, the regenerative activity observed with prior LCCl4 administration was remarkably greater, particularly at 48 hr. Colchicine preadministration in either of these 2 protocols decisively obtunded the stimulated regenerative activities essentially abolishing the tissue healing mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)

A single administration of a subtoxic dose of CCl4 (100 microliters/kg, i.p.) is known to induce hepatocellular regeneration and tissue repair at 6 and 48 h in rats, permitting prompt recovery from the limited liver injury associated with that dose of CCl4. Substantial evidence has accumulated to indicate that the early-phase hepatocellular regeneration and tissue repair are critical for recovery from halomethane hepatotoxicity. The objective of these studies was to test this concept in an experimental framework, wherein a selective ablation of the early-phase cell division should result in prolongation of liver injury followed by recovery. The studies were designed to evaluate the influence of the antimitotic agent colchicine (1 mg/kg, i.p. in saline) on CCl4 toxicity. Colchicine was administered 2 h prior to CCl4 or corn oil injection. Toxicological end points and markers of hepatocellular regeneration were assessed at various time points (2, 6, 12, 24, 48 and 72 h) after the injection of CCl4 to male Sprague-Dawley rats. Hepatocellular injury was assessed through elevations of serum alanine and aspartate aminotransferase and by histopathological examination of the liver. Incorporation of 3H-thymidine in hepatocellular nuclear DNA and mitotic index were used as indices of hepatocellular regeneration. Hepatocellular regeneration stimulated by CCl4 at 2-6 h was blocked by colchicine as evidenced by the decreased 3H-thymidine incorporation and mitotic index,without any significant effect on the second phase of cell division at 48 h. Ablation of this early phase of tissue repair resulted in prolongation of CCl4 hepatoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Background:Oral submucous fibrosis is one of the most commonly occurring potentially malignant disorders in the South-East Asia. Levels of lipid peroxidation product malondialdehyde have been recently correlated with clinical grades of oral Submucous fibrosis.Aims:The aims of this study were to estimate the levels of malondialdehyde in serum, saliva and tissue in patients with oral submucous fibrosis, to correlate change in levels of malodialdehyde with the histopathological grading.Materials and Methods:The study group comprised of 65 clinically diagnosed and histopathologically confirmed cases of oral submucous fibrosis, 21 age and sex matched controls were also enrolled into the study. The serum saliva and tissue samples in the study groups were evaluated by the thiobarbutric acid reactive substances.Results:There was a significant difference between the serum and salivary malondialdehyde among the histopathological grades of oral submucous fibrosis. Tissue malonaldehyde levels were significantly higher as the grading progressed but tissue levels in grade 3 oral submucous fibrosis were lower than the controls.Conclusion:This decrease in tissue malonaldehyde could possibly be associated to collagen cross linking occurring during the advanced stages of oral submucous fibrosis.

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The objective of the present study was to optimise the biosynthesis of gold nanoparticles using aqueous extract of Pongamia seed cake (PSC). Proteins, amino acids and phenolic compounds present in the PSC extract are responsible for reducing the metal precursor salt to nanoparticles. The levels of factors for optimisation of nanoparticles synthesis was evaluated using UV-Vis spectrophotometer by one factor at a time studies. Further factorial design was employed to study the significant effect of various parameters on the nanoparticles synthesis. The levels of two significant factors i.e. pH and concentration of PSC extract as obtained from factorial design were optimized further for maximum nanoparticle synthesis applying central composite design. The optimized conditions were found to be pH 3.6 and PSC extract concentration of 17.07% (w/v) at which an increase (OD at 530 nm = 1.3) in nanoparticle synthesis was observed as compared to un-optimized conditions (OD at 530 nm = 0.66). The model obtained on optimization was validated and it describes the nanoparticle synthesis aptly with an error between experimental and predicted values of just 1.15% with an R 2 of 0.985. It can be concluded that, RSM approach was found to be an efficient technique to optimize the reaction conditions, where a twofold increase in synthesis of small sized monodispersed gold nanoparticles was seen.Electronic supplementary material The online version of this article (https ://doi.

Pongamia pinnata, a tree bearing oil seeds, has been one of the prime focus among nonedible oil sources for biodiesel production in most parts of India. The oil cake obtained after the extraction of oil serves as an adequate source of cellulose, hemicellulose, proteins, lipids, and starch. The scarce literature data available suggest very low conversion rate of complex sugars to fermentable sugars and further to bioethanol. In the present work, a sulfuric acid hydrolysate obtained from Pongamia oil cake (POC) under microwave irradiation was anaerobically fermented using Bacillus cereus ATCC 14579. Under anaerobic and acidic conditions, the process parameters affecting the bioethanol production efficiency (BPE) were screened and optimized using statistical experimental designs. Of the seven parameters screened (glucose concentration, yeast extract as nitrogen source, agitation speed, pH, inoculum size, fermentation time, and temperature), only 3 were found to be significant and to increase BPE. The significant parameters were optimized using the Box-Behnken experimental design to obtain an optimal condition of 9 g/l reducing sugars, pH 4.6 maintained with acetate buffer, and fermentation period of 51 h that yielded 92% BPE with 4.2 g/l ethanol. Moreover, it was observed that the use of a buffer system to maintain broth pH, especially acetate buffer, significantly improved BPE. Low concentration of fermentation inhibitors is the key factor for improved BPE. The research outcome suggests that the production of dual fuel from Pongamia pinnata, viz. biodiesel and bioethanol, could not only improve the process economics but also reduce waste generation.