Hepatitis & Nanomedicine: A Review

In the year 1989, hepatitis C virus (HCV) was specifically established as causative factor accountable for many more occurrences of hepatitis. It's a chronic disease which majorly contributes to Carcinoma and Cirrhosis. The hepatitis C virus belongs a family Flaviviridae (+) enveloped ssRNA virus. It has been described that seven major genotypes of HCV and their subtypes (a, b). Around 3 percent among global residents has been infected by HCV. HCV Transmission is frequently associated with direct percutaneous blood contact, via blood transfusions, health-related injections and substance use injections. Several new therapies have been developed to treat HCV, such as polyethylene glycol (PEG)-ylated interferon / ribavirin, antivirals acting directly and antivirals targeting the host. Despite progress in anti-HCV therapy, there is still an urgent need for new approaches of targeted drug delivery systems using nanomedicine which are affordable and reliable. Nanotechnology has the ability to play a pivotal role in lowering viral load levels and drug-resistant HCV by targeting drugs directly to the disease site. In addition to tissue targeting, a wide variety of drugs need to be administered intracellularly to achieve a therapeutic effect in the organ affected. The contribution of nanoparticles as a promising delivery mechanism for HCV immunizing, diagnostic and therapeutic agents and there latest developments of drug carriers as well as their role in anti-HCV therapy were addressed in this review.

Probiotic Potential And Safety Characterization Of Enterococcus Hirae G24 Isolated From Indigenous Raw Goat Milk

In this paper, an investigation on lactic acid bacterial isolates from ethnic goat raw milk samples were examined for their probiotic potential and safety parameters. For this purpose, isolated bacterial cultures were screened based on certain parameters viz., sugar fermentation, tolerance to temperature, salt, low pH, bile salts, and phenol resistance. After that, these bacterial cultures were more estimated in vitro for auto-aggregation, cell surface hydrophobicity, response to simulated stomach duodenum channel, antibiotic resistance, and antimicrobial activity. Besides, probiotic traits show the absence of gelatinase and hemolytic activity supports its safety. The isolate G24 showed good viability at different pH, bile concentration, phenol resistance and response to simulated stomach duodenum passage but it did not show gelatinase and hemolytic activities. Isolate G24 was susceptible to amikacin, carbenicillin, kanamycin, ciprofloxacin, co-trimazine, nitrofurantoin, streptomycin, and tetracycline. Isolate G24 also exhibited antimicrobial action against five common pathogenic bacteria, such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogens, and Salmonella typhimurium. It displayed the maximum auto-aggregation, cell surface hydrophobicity to different hydrocarbons. Following molecular characterization the isolate G24 was identified as Enterococcus hirae with 16S rRNA gene sequencing and phylogeny. E. hirae G24 bears the excellent properties of probiotics.

The role of linoleic acid, palmitic acid and leucine in lipstatin biosynthesis by streptomyces toxytricini.

Lipstatin, a new and very potent inhibitor of pancreatic lipase, was isolated from the Streptomyces toxytricini. Lipstatin contain a beta lactone structure that probably account for the irreversible lipase inhibition. As per the biosynthetic pathway the role of linoleic acid, palmitic acid and leucine in lipstatin biosynthesis by Streptomyces toxytricini was studied. Different oils were analyzed to measure the concentration of the linoleic acid and palmitic acid in the medium, and then the selected oil was used as media ingredients. While leucine was used as a media ingredient as well as feeding nutrient in the production medium. The lipstatin production depends on linoleic acid palmitic acid and leucine concentration as per biochemical pathway. But in present study it was observed that in control media the lipstatin activity was 1.108 mg/g while when we use linoleic acid and palmitic acid as media ingredients then the activity was 0.610 mg/g. Similarly in case of leucine was used as ingredient as well as feeding solution the maximum activity was observed 0.810 mg/g at 264 h. Thus, it may conclude that their is no significant impact of linoleic acid, palmitic acid and leucine as media ingredients and as a feeding solution on lipstatin production.

Food reduces the bioavailability of lamotrigine.

BACKGROUND AND OBJECTIVE: Lamotrigine is a relatively newer antiepileptic drug used in the treatment of partial seizures. It has a narrow therapeutic index and hence the achieved blood level of the drug is closely related to the therapeutic efficacy and toxicity. The bioavailability of lamotrigine is affected by food, hence the present study was done to investigate the effect of two types of food on the bioavailability of lamotrigine. METHODS: A randomized, open-label, three treatment, three period, single dose and cross-over study was done in nine healthy male volunteers. A single dose of lamotrigine (100 mg) was administered at three occasions: after a north Indian diet (high calorie, high fat), after a south Indian diet (low calorie, low fat), and after an overnight fasting. Serial blood samples were collected up to 24 h post dose. Plasma lamotrigine concentrations were determined and pharmacokinetic parameters studied. RESULTS: A statistically significant decrease in rate and extent of absorption was observed with north Indian diet and south Indian diet when compared with fasting group. Presence of both types of food causes decrease in mean values of C(max), AUC((0-t)), and AUC((0-alpha)) thus reducing the bioavailability of lamotrigine at significant level (P<0.05). INTERPRETATION AND CONCLUSION: Lamotrigine should be taken preferably in fasting condition, as presence of food (low fat, low calorie or high fat, high calorie) decreases the bioavailability to a significant extent.

Antagonistic effect of fluorescent pseudomonads against Macrophomina phaseolina that causes charcoal rot of groundnut.

Maximum colony growth inhibition was observed due to Pseudomonas PS2 (74%) as compared to PS1 (71%) on trypticase soy agar (TSM) plates after 5 days of incubation. Light and scanning electron microscopic examination showed hyphal coiling, vacuolation, coagulation and granulation of cytoplasm resulting in lysis of hyphae of M. phaseolina by pseudomonads. Cell free culture filtrates of strains PS1 and PS2 restricted the growth of mycelium of M. phaseolina. PS1 and PS2 caused maximum colony growth inhibition by 57 and 61% respectively at 20% concentration of culture filtrate after 4 days of incubation. Volatile substances produced by PS1 and PS2 also inhibited the colony growth of M. phaseolina by 25 and 32%, respectively. Inhibitory effect of volatile substances, however, decreased with advancing in incubation period. Colony growth of M. phaseolina was significantly decreased by PS1 and PS2 as compared to control both in iron- sufficient and iron-deficient conditions. PS2 showed higher antagonistic activity than PS1, as evidenced by pronounced colony growth inhibition.

Effect of metal ions on growth of Pseudomonas aeruginosa and siderophore and protein production.

Pseudomonas aeruginosa (GRC1) isolated from potato rhizosphere, grew better on succinate medium than tryptic soy medium and produced hydroxamate type of siderophore in iron-deficient succinate medium. When the strain GRC1 was grown in the presence of different metal ion compounds, viz. ZnSO4, MnSO4, MnCl2 and FeCl3 at 6 and 12 microM concentrations individually, ZnSO4 (12 microM) promoted siderophore production but suppressed the growth and protein content of test organism. MnCl2 and FeCl3 (12 microM) enhanced the growth, whereas MnCl2 and MnSO4 (12 microM) induced protein contents of strain GRC1.

Alkyl ester prodrugs for improved topical delivery of ibuprofen.

Topical delivery of ibuprofen directly to the site of inflammation can overcome gastrointestinal side effects associated with its long term oral administration. The set of physicochemical properties necessary for optimum topical delivery of ibuprofen can be imparted by formation of its ester prodrugs. Various alkyl ester prodrugs (methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-buty, n-pentyl, hexyl, heptyl, octyl, lauryl, cetyl and octadecyl esters) were synthesised and studied for their physicochemical properties and activity in the carrageenan induced rat paw oedema by topical route. Favourable shift in lipophilicity and self penetration enhancing effect of prodrugs responded in improved topical activity over the parent drug ibuprofen.

Intestinal giardiasis: an unusual cause for hypoproteinemia.

Malabsorption is a well-known complication of infection with Giardia lamblia. However, selective protein-losing enteropathy is rare. We report a child with anasarca due to hypoalbuminemia as a result of gastrointestinal protein loss. Investigations established giardiasis as the etiology. The child returned to normal health after treatment with metronidazole.

Significance of charge on lysine residue of ovine luteinizing hormone on immunological and biological properties of the hormone.

In order to understand the significance of positive charge of lysine residues of ovine luteinizing hormone (oLH) on immunological and biological activity, the epsilon-NH2 group(s) of ovine LH were sequentially modified with 2-iminothiolane (2IT) that preserves the positive charge of the lysine while the overall charge of the hormone remains unchanged. These studies have also been compared with the oLH modified by N-succinimidyl 3-(2 pyridyldithio) propionate (SPDP) and succinimidyl 6-[3-(2-pyridyldithio)propionamido]hexanoate (LC-SPDP) that abolish positive charge of lysine residues. The modification primarily occurs in the alpha-subunit. Sequential modification led to progressive reduction in receptor binding and immunological activities. However, the steroidogenic activity was substantially retained. The immunoreactivity and receptor binding properties of 2IT modified oLH (oLH-2IT) were less affected when compared to SPDP (oLH-SPDP) or LC-SPDP (oLH-LC-SPDP) modified derivatives suggesting that increase in hydrophobic carbon chain in oLH-LC-SPDP molecule resulted in drastic inhibition in immunological and biological properties. But the steroidogenic potential of oLH-2IT, oLH-LC-SPDP or oLH-SPDP was relatively comparable. This suggests that a single -NH2 group modification with 2IT would generate the site in the hormone for conjugation to the toxin/carrier proteins that may retain better immunological and biological activity compared to that of SPDP or LC-SPDP modified oLH.

Purification and characterisation of gelonin from seeds of Gelonium multiflorum.

Gelonin, a ribosome-inactivating protein has been isolated from the seeds of Gelonium multifluorum of Euphorbiaceae family by two methods and the results are compared. In method-I conventional aqueous extraction, cation-exchange and gel-filtration chromatography has been used. In method-II S-Sepharose fast flow gel has been used to purify the proteins from the seed extract, followed by ammonium sulfate fractionation, cation-exchange and gel-filtration chromatography. Extensive physico-chemical and immunological characterizations show that molecular weight of gelonin as determined by gel-filtration chromatography and SDS-PAGE is approximately 30 kDa. The non-proteinous material which binds to CMC-gel in association with gelonin in method-I is substantially removed when gelonin is purified by method-II. Cation exchange, G-100 chromatography, RP-HPLC and SDS-PAGE show that method-II yields 50% more purified gelonin when compared to the yield by method-I. The immunoreactivity of gelonin obtained by methods I and II vary from 22-26% and 50-66% respectively and the ribosome-inactivating property vary from 46-56% and 70-87% respectively.

Synergistic effects in enzymic reactions.

It has been shown that when two enzymes showing similar actions act in close proximity of each other they influence each other synergistically. The phenomenon of synergism is, however, not observed if the two enzymes are of dissimilar action type. The condition of closest proximity has been simulated by conducting the enzymic reactions inside the reversed micelles. In the present study we have experimented with alpha-amylase and invertase both hydrolysing enzymes and also with peroxidase and invertase which do not show similar actions.

Prevalence of chronic lymphocytic thyroiditis in adolescent girls.

Chronic lymphocytic thyroiditis (CLT) is the most common cause of thyroid enlargement in children and adolescents in iodine sufficient areas. The prevalence and pattern of CLT in adolescent girls in iodine deficient regions supplemented with iodine is as yet not known. We therefore, carried out clinical examination for the presence of goitre in 330 healthy girls from Delhi in the age group of 16-20 years and those with goitre were further subjected to detailed biochemical (T3, T4, TSH), immunological (ATg ad ATm) and cytomorphological examination. The prevalence of goitre was found to be 40%. Fine needle aspiration cytology (FNAC) carried out in 94 girls with goitre (74%) revealed finding consistent with CLT in 13 (13.8%), colloid goitre with non-specific thyroiditis in 7 (7.4%), colloid goitre in 71 (75.5%) and specimen was inadequate in 3 (3.2%) girls. Thyroid antibodies were estimated in 114 of the goitrous subjects and both ATg and ATm were positive in 11 (9.6%) cases. Overall prevalence of CLT in this population was 4.0% and among those with goitre was 13.8%. When thyroid antibodies were also considered as an indicator of thyroiditis, prevalence rose to 14.4% among goitrous girls. Thyroid function tests were found to be within normal limits in all goitrous girls. This study for the first time reveals a high prevalence of CLT in goitrous adolescent girls from iodine supplemented region and underscores the need to study the prevalence of CLT in different age and sex groups from different regions of the country.

Fungitoxic action of dithanes in presence of surfactant micelles.

A rationale of arriving at the concentration of surfactant additives in the pesticidal formulations has been discovered. Fungitoxic activity of each of the two dithanes, Dithane M-45 (maneb) and Dithane Z-78 (zineb) has been estimated in the presence of various concentrations of three surfactants namely sodium lauryl sulphate, cetyl pyridinium chloride and Tween 80. Data reveal that the concentration of the surfactant additives in the pesticidal formulations should be at least equal to its critical micelle concentration (CMC) for enhanced biological activity. This rationale for the concentration of surfactant additives in the pesticidal formulation has so far not been clearly brought out in the literature. Since biological activity of the pesticides is enhanced in the presence of surfactant additives the present study is relevant to the reduction of environmental pollution due to pesticide residues.

Antifertility activity of Ailanthus excelsa Linn. in female albino rats.

Alcoholic extract of leaf and stem bark of A. excelsa at a dose of 250 mg equivalent of plant material/kg body weight, exhibited remarkably high anti-implantation and early abortifacient activities. The results are in agreement with the traditional use of this plant as a abortifacient by the Irula women of the Nilgiri district.

Effect of some antibiotics on Macrophomina phaseolina, a charcoal rot fungus of soybean.

Effect of agrimycin-100, ampicillin, griseofulvin and tetracycline on colony growth of Macrophomina phaseolina, incitant of charcoal rot of soybean has been studied in vitro. Amongst them tetracycline posed most effective inhibiting the growth by 73.9% at 1000 micrograms/ml concentration. On the basis of effectiveness antibiotics have been listed as tetracycline greater than ampicillin greater than griseofulvin greater than agrimycin-100.