Effect of ursodeoxycholic acid on hydrogen peroxide induced lipid peroxidation in sheep liver mitochondria

The effect of various concentrations of ursodeoxycholic acid (UDCA), a potent hepatoprotective agent on hydrogen peroxide-induced mitochondrial swelling was evaluated in vitro to find out the mechanism of action of the drug. Aliquots of sheep liver mitochondria were pre-incubated with various concentrations of UDCA [0-600 micrograms] and swelling was induced by hydrogen peroxide [1 mM]. Swelling was assessed at various time intervals and lipid peroxide, reduced glutathione status were also evaluated simultaneously. UDCA minimized hydrogen peroxide-induced swelling in a dose-dependent manner. Time-dependent elevation in the level of lipid peroxides was noted in mitochondria treated with hydrogen peroxide and this elevation was minimized in UDCA pre-treatment. UDCA also maintains the reduced glutathione level in mitochondria. UDCA acts against the oxidative stress imposed in liver mitochondria. It reduces lipid peroxidation-induced abnormalities such as swelling and thiol group depletion and the anti lipid peroxidative efficacy of the drug may be related to its hydrophilic nature which might protect the hydrophobic regions of the mitochondrial membranes which are prone for free radical-mediated reactions.     

Studies on the development of colon-targeted delivery systems for celecoxib in the prevention of colorectal cancer

The nonsteroidal anti-inflammatory drugs (NSAIDs) are found to be potential chemopreventive agents of colorectal cancer. Celecoxib, an NSAID with selective cyclooxygenase-2 inhibition, was proved to be effective for the prevention of colon cancer in patients with familial adenomatous polyposis (FAP) and sporadic polyps. In the light of this information, the present study was carried out to develop oral colon-targeting drug delivery systems for celecoxib using guar gum as a carrier. Matrix tablets containing various proportions of guar gum were prepared by wet granulation technique using starch paste as a binder. The tablets were evaluated for hardness, drug content and were subjected to in vitro drug release studies. The amount of celecoxib released from the matrix tablets at different time intervals was estimated by a HPLC method. Guar gum matrix tablets released only 2-4% of celecoxib in the physiological environment of stomach and small intestine depending on the proportion of guar gum used in the formulation. When the dissolution study was continued in simulated colonic fluids (rat caecal content medium), the matrix tablets containing 20% of guar gum released another 37% of celecoxib after degradation by the colonic bacterial action. The matrix tablets containing 30% of guar gum released about 24% of celecoxib in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that the matrix tablets containing either 20 or 30% of guar gum are most likely to target celecoxib for local action in the colon. The guar gum matrix tablets of celecoxib showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40 degrees C/RH 75% for 6 months. Differential scanning calorimetry (DSC) studies indicated no possibility of interaction between celecoxib and guar gum/other formulation excipients.     

Disseminated and disfiguring molluscum contagiosum in a child

We report widely disseminated and disfiguring lesions of molluscum contagiosum occurring in a 4-year-old girl secondary to a primary immunodeficiency disorder. The child, born of consanguineous parents, had multiple, asymptomatic, raised, skin-colored and whitish lesions since 2 years of age. On physical examination she had growth retardation features with grade II protein energy malnutrition. Cutaneous examination revealed numerous, widespread, skin-colored to translucent, firm, umbilicated papules of varying sizes (pinpoint to larger than 10 mm). They were distributed bilaterally over all four limbs, including the dorsum of the hands and feet, trunk, face (including lips), eyelids, auriculae, and perineal and gluteal areas. In places, they were linearly disposed and had coalesced to form plaques. A biopsy specimen from a representative skin lesion (arm) demonstrated lobulated epidermal growth consisting of keratinocytes with large intracytoplasmic eosinophilic inclusion bodies and a central crater. These findings were consistent with the diagnosis of molluscum contagiosum. Topical therapies with phenol and trichloroacetic acid were ineffective The child succumbed to a fulminant systemic infection at home, 2 months after discharge from the hospital. The extent and distribution of molluscum contagiosum in our patient was remarkably vivid and has been hitherto reported only rarely.     

Protective effect of propyl gallate against myocardial oxidative stress-induced injury in rat

This study was designed to investigate the effect of chronic administration of propyl gallate on myocardial oxidative stress-induced injury. Propyl gallate was administered orally to Wistar albino rats (150-200 g) in three different doses, by gastric gavage (250 mg kg(-1) (P1), 500 mg kg(-1) (P2) and 750 mg kg(-1) (P3)), 6 days a week for 5 weeks. At the end of this period, all the rats, except the normal untreated rats that served as the control group, were administered isoproterenol (ISO), 85 mg kg(-1) subcutaneously, for 2 consecutive days to induce myocardial injury. After 48 h, rats (n = 6 per group) were anaesthetized with anaesthetic ether, sacrificed and the hearts were harvested for the estimation of thiobarbituric acid reactive substances (TBARS), endogenous antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD) and catalase) and for the assessment of histological changes. In the P2 BL group (BL = baseline), there was a significant (P < 0.001) rise in baseline TBARS and SOD when compared with the saline-treated group, while no such changes were observed in the other baseline-treated groups. However, there was a significant (P < 0.001) increase in TBARS and endogenous anti-oxidants (GSH, SOD and catalase) in the P2 ISO and P3 ISO groups, when the hearts were subjected to in-vivo myocardial oxidative stress-induced injury. We observed no such changes in the P1 ISO group. This study showed that propyl gallate modulates the levels of endogenous antioxidants present at the myocardial site. Whether these modifications are a result of direct interference at this site or a remote effect is not immediately clear. In conclusion, from the results it could be stated that chronic administration of 500 mg kg(-1) of propyl gallate offers significant protection against myocardial oxidative stress-induced injury.     

Synthesis, characterization and antimicrobial activity of some substituted 1,2,3-triazoles

Two substituted 1,2,3-triazoles 4 and 6 have been synthesized by the 1,3-dipolar cycloaddition reaction of 4-azido-8-(trifluoromethyl)quinoline 2 with ethyl acetoacetate and acetylacetone, respectively. The reaction of 2 with ethyl acetoacetate afforded 1-[8-(trifluoromethyl)quinolin-4-yl]-5-methyl-1H-1,2,3-triazole-4-carboxylic acid 3 and with acetylacetone afforded 1-{1-[8-(trifluoromethyl)quinolin-4-yl]-5-methyl-1H-1,2,3-triazol-4-yl}ethanone 5. Compound 3 is converted into its corresponding acid hydrazide and then condensed with different aromatic aldehydes to yield Schiff's base, N-[1-arylmethylene]-1-[8-(trifluoromethyl)quinolin-4-yl]-5-methyl-1H-1,2,3-triazole-4-carbohydrazides 4. Compound 5 is condensed with aromatic aldehydes to obtain [1-aryl-4-{1-[8-(trifluoromethyl)quinolin-4-yl]-5-methyl-1H-1,2,3-triazol-4-yl}prop-2-en-1-ones 6. The newly prepared 1,2,3-triazole derivatives 4 and 6 have been characterized by IR, NMR and mass spectral data. These compounds were screened for their antimicrobial activity.