Showing papers by "Manoj Kumar published in 2012"

A review of permissible limits of drinking water

Abstract: Water is one of the prime necessities of life. We can hardly live for a few days without water. In a man's body, 70-80% is water. Cell, blood, and bones contain 90%, 75%, and 22% water, respectively. The general survey reveals that the total surface area of earth is 51 crore km 2 out of which 36.1 crore km 2 is covered sea. In addition to this, we get water from rivers, lakes, tanks, and now on hills. In spite of such abundance, there is a shortage of soft water in the world. Physicochemical parameter of any water body plays a very important role in maintaining the fragile ecosystem that maintains various life forms. Present research paper deals with various water quality parameter, chlorides, dissolved oxygen, total iron, nitrate, water temperature, pH, total phosphorous, fecal coli form bacteria, and adverse effect of these parameters on human being.

Probiotics, their health benefits and applications for developing healthier foods: a review

Abstract: In the industrialized world, functional foods have become a part of an everyday diet and are demonstrated to offer potential health benefits beyond the widely accepted nutritional effects. Currently, the most important and frequently used functional food compounds are probiotics and prebiotics, or they are collectively known as ‘synbiotics’. Moreover, with an already healthy image, dairy products appear to be an excellent mean for inventing nutritious foods. Such probiotic dairy foods beneficially affect the host by improving survival and implantation of live microbial dietary supplements in the gastrointestinal flora, by selectively stimulating the growth or activating the catabolism of one or a limited number of health-promoting bacteria in the intestinal tract, and by improving the gastrointestinal tract's microbial balance. Hence, the paper reviews the current scenario of probiotics and their prospective potential applications for functional foods for better health and nutrition of the society.

Cholesterol-Lowering Probiotics as Potential Biotherapeutics for Metabolic Diseases

Abstract: Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels and the risks of coronary heart disease. Current dietary strategies for the prevention of cardiovascular disease advocate adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in experimental conditions, low-fat diets offer an effective means of reducing blood cholesterol concentrations on a population basis, these appear to be less effective, largely due to poor compliance, attributed to low palatability and acceptability of these diets to the consumers. Due to the low consumer compliance, attempts have been made to identify other dietary components that can reduce blood cholesterol levels. Supplementation of diet with fermented dairy products or lactic acid bacteria containing dairy products has shown the potential to reduce serum cholesterol levels. Various approaches have been used to alleviate this issue, including the use of probiotics, especially Bifidobacterium spp. and Lactobacillus spp.. Probiotics, the living microorganisms that confer health benefits on the host when administered in adequate amounts, have received much attention on their proclaimed health benefits which include improvement in lactose intolerance, increase in natural resistance to infectious disease in gastrointestinal tract, suppression of cancer, antidiabetic, reduction in serum cholesterol level, and improved digestion. In addition, there are numerous reports on cholesterol removal ability of probiotics and their hypocholesterolemic effects. Several possible mechanisms for cholesterol removal by probiotics are assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface, incorporation of cholesterol into the cellular membrane, deconjugation of bile via bile salt hydrolase, coprecipitation of cholesterol with deconjugated bile, binding action of bile by fibre, and production of short-chain fatty acids by oligosaccharides. The present paper reviews the mechanisms of action of anti-cholesterolemic potential of probiotic microorganisms and probiotic food products, with the aim of lowering the risks of cardiovascular and coronary heart diseases.

Protein tyrosine phosphatase 1B inhibitors: a molecular level legitimate approach for the management of diabetes mellitus.

Abstract: Diabetes mellitus is a systemic disease responsible for morbidity in the western world and is gradually becoming prevalent in developing countries too. The prevalence of diabetes is rapidly increasing in industrialized countries and type 2 diabetes accounts for 90% of the disease. Insulin resistance is a major pathophysiological factor in the development of type 2 diabetes, occurring mainly in muscle, adipose tissues, and liver leading to reduced glucose uptake and utilization and increased glucose production. The prevalence and rising incidence of diabetes emphasized the need to explore new molecular targets and strategies to develop novel antihyperglycemic agents. Protein Tyrosine Phosphatase 1B (PTP 1B) has recently emerged as a promising molecular level legitimate therapeutic target in the effective management of type 2 diabetes. PTP 1B, a cytosolic nonreceptor PTPase, has been implicated as a negative regulator of insulin signal transduction. Therefore, PTP 1B inhibitors would increase insulin sensitivity by blocking the PTP 1B-mediated negative insulin signaling pathway and might be an attractive target for type 2 diabetes mellitus and obesity. With X-ray crystallography and NMR-based fragment screening, the binding interactions of several classes of inhibitors have been elucidated, which could help the design of future PTP 1B inhibitors. The drug discovery research in PTP 1B is a challenging area to work with and many pharmaceutical organizations and academic research laboratories are focusing their research toward the development of potential PTP 1B inhibitors which would prove to be a milestone for the management of diabetes. © 2010 Wiley Periodicals, Inc. Med Res Rev, 32, No. 3, 459–517, 2012

Anticarcinogenic effect of probiotic fermented milk and chlorophyllin on aflatoxin-B₁-induced liver carcinogenesis in rats.

Abstract: The present investigation was carried out to evaluate the hepatoprotective effect of probiotic fermented milk (FM) containing Lactobacillus rhamnosus GG and Lactobacillus casei strain Shirota, alone as well as in combination with chlorophyllin (CHL) as an antioxidant agent in male Wistar rats administered aflatoxin-B₁ (AFB₁). AFB₁ was injected intraperitoneally at the rate of 450 μg/kg body weight per animal twice a week for 6 weeks, maintaining an equal time interval between the two consecutive AFB₁ administrations. A total of 125 male Wistar rats were randomly allocated to five groups, each group having twenty-five animals. Group I was offered FM containing L. rhamnosus GG and L. casei strain Shirota. Group II was administered AFB1 and served as the control group; group III was administered FM-AFB₁, in which besides administering AFB₁, FM was also offered. Group IV was offered CHL and AFB₁, and group V was offered both FM and CHL along with AFB₁. The rats were euthanised at the 15th and 25th week of the experiment and examined for the biochemical and hepatopathological profile. A significant reduction in thiobarbituric acid-reactive substances (TBARS) was observed in the FM-CHL-AFB₁ group compared with the AFB1 control group. FM alone or in combination with CHL was found to show a significant (P < 0·05) hepatoprotective effect by lowering the levels of TBARS and by enhancing the activities of antioxidant enzymes such as glutathione peroxidase, superoxide dismutase, catalase and glutathione-S-transferase, indicating that probiotic FM alone or in combination with CHL possesses a potent protective effect against AFB₁-induced hepatic damage.

Milk, milk products, and disease free health: an updated overview

Abstract: The cow and its milk have been held sacred in the world since the dawn of human civilization. Indian ancient Vedic texts describe the virtues of milk and dairy products, as is authenticated by modern scientific principles and proofs. Therefore, milk has been considered as one of the most natural and highly nutritive part of a daily balanced diet. Currently, the integration of advanced scientific knowledge with traditional information is gaining incredible momentum toward developing the concept of potential therapeutic foods. Furthermore, new advances toward understanding the therapeutic roles of milk and milk products have also given a new impetus for unraveling the age old secrets of milk. At present, the best-known examples of therapeutic foods are fermented milk products containing health promoting probiotic bacteria. In the present article, we have tried to review the various aspects of the therapeutic nature of milk and fermented dairy products in a highly up-dated manner, and offer an in-depth insight into the development of targeted therapeutic future foods as per the requirements of consumers.

Indole-based fibrates as potential hypolipidemic and antiobesity agents.

Abstract: Hypolipidemic and antiobesity effects of the newly synthesized indole-based fibrates were evaluated in Triton WR-1339 and high fat diet (HFD)-induced hyperlipidemic rats. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton model), in which compounds 3f and 3l showed significant antidyslipidemic activity. Furthermore, these compounds 3f and 3l were found to induce significant weight loss in the visceral fat mass of HFD-fed hyperlipidemic rats without affecting the normal feeding behavior. Histological examination of the liver of rats supplemented with 3f and 3l revealed a significant decrease in steatosis when compared to the effect of the standard drug fenofibrate. Additional effects such as an increase in lecithin cholesterol acyl-transferase (LCAT) enzyme level and increased receptor mediated catabolism of I131-low density lipoproteins (LDL) confirm and reinforce the efficacy of both of these compounds as a new class of dual-acting hypolipidemic and antiobesit...

Fortification and fermentation of fruit juices with probiotic lactobacilli

Abstract: In present investigation, two Lactobacillus isolates, viz. L. plantarum and L. acidophilus, were observed to be able not only to survive but to utilize fruit juices for their cell synthesis, as indicated by a decrease in fruit sugar and pH, and increase in acidity. L. acidophilus was found to consume the sugar at a faster rate than L. plantarum, although the fall in sugar and pH and increase in acidity was faster during the first 24 h and became a little slower during the next 48 h, which could be due to the accumulation of too much acid during the initial 24 h of fermentation. Still, both cultures were found to be able to survive in fermented juices with high acidity and low pH. Therefore, it could be concluded that such probiotic-fortified fruit juices could certainly be exploited as a medium for the delivery of probiotics, and could be used as a functional healthy beverage to promote better health and nutrition of the population, especially for those who are allergic or intolerant to milk-based products.

Tongue-tie, breastfeeding difficulties and the role of Frenotomy.

Abstract: A greater emphasis on exclusive breastfeeding in recent years has re-ignited the historical debate over the role of ankyloglossia (tongue-tie) in infants with breastfeeding difficulties. Several prospective cohort studies and randomized control trials have been published in this area in the last 10–15 years. We critically evaluated recent evidence and attempted to answer two important clinical queries in this area, that is, (i) whether ankyloglossia is associated with breastfeeding difficulties and (ii) whether frenotomy helps mother–baby dyad in such setting? Conclusion: Neonates with tongue-tie are at increased risk for breastfeeding difficulties. An early recognition of this association by primary care provider and prompt referral to a lactation consultant is important. In cases with clearly documented breastfeeding difficulties, frenotomy often results in rapid improvement in symptoms.

Detection of Epigenetic Variations in the Protoplast-Derived Germlings of Ulva reticulata Using Methylation Sensitive Amplification Polymorphism (MSAP)

Abstract: Regeneration of protoplasts into de novo plants was reported for a large number of seaweed species. The regeneration of protoplasts into different morphotypes as a result of epigenetic variations was discussed for the first time in this study. The loci assessed for methylation modifications in normal filamentous thalli showed a frequency of 32.43% as unmethylated DNA, 24.32% as a hemimethylated, and 20.27% as a methylation of internal cytosine at both the strands. The corresponding methylation values for disk-type thalli were 27.02%, 32.43%, and 14.86%, respectively. The hypermethylation condition was apparent in the disk-type thalli with methylation ratio of 72.97% compared to that of normal filamentous thalli with 67.56%. The frequency of methylation polymorphic sites among the two morphotypes was 53%. The present study reveals the distinct expression of cytosine methylation and is thus correlated to differential morphogenesis of plants regenerated from cultured cells. The number of protoplasts regenerating into filamentous thalli declined with increasing temperature from 15°C, 20°C, 25°C, and 30°C. The disk-type variant had higher thermal stability at 30°C over normal filamentous thalli. Further, this variant could maintain itself for more than a year in the laboratory indicating its suitability for in vitro germplasm maintenance and propagation.

A Simple and Efficient Access to New Functionalized 4‐Phenacylideneflavenes#

Abstract: An innovative and efficient approach towards diversity-oriented synthesis of 4-phenacylideneflavenes has been developed from substituted salicylaldehydes and acetophenones using iodine under solvent-free conditions. Both symmetrical and unsymmetrical functionalized 4-phenacylideneflavenes were synthesized in good to excellent yields and their mechanism of formation is discussed.

Solution-phase detection of dual microRNA biomarkers in serum.

Abstract: A strategy for the simultaneous detection of multiple microRNA (miRNA) targets was developed utilizing fluorophore/quencher-labeled oligonucleotide probe sets. Two miRNA targets (miR-155 and miR-103), whose misregulation has afforded them status as putative biomarkers in certain types of cancer, were detected using our assay design. In the absence of target, the complementary fluorophore-probe and quencher-probe hybridize, resulting in a fluorescence resonance energy transfer-based quenching of the fluorescence signal. In the presence of unlabeled target, however, the antisense quencher-probe can hybridize with the target, resulting in increased fluorescence intensity as the quencher-probe is sequestered beyond the Forster radius of the fluorescent-probe. The assay design was tested in multiple matrices of buffer, cellular extract, and serum; and detection limits were found to be matrix-dependent, ranging from 0.34 to 8.89 pmol (3.4-59.3 nM) for miR-155 and 2.90-11.8 pmol (19.3-79.0 nM) for miR-103. Single, double, and triple nucleotide selectivity was also tested. Additionally, miR-155 concentrations were assessed in serum samples obtained directly from breast cancer patients without the need for RNA extraction. This assay is quantitative, possesses a low detection limit, can be applied in multiple complex matrices, and can obtain single-nucleotide selectivity. This method can be employed for the multiplex detection of solution-phase DNA or RNA targets and, more specifically, for the direct detection of serum miRNA biomarkers.

Is there an association between fetal scalp electrode application and early-onset neonatal sepsis in term and late preterm pregnancies? A case-control study.

Abstract: Objective Early-onset neonatal sepsis (EONS), defined as neonatal sepsis occurring within the first week after birth, is a major cause of morbidity and mortality. Fetal scalp electrode application, used for fetal heart rate monitoring during labour, could potentially increase the risk of EONS. The objective of this study was to determine whether this practice is associated with a significant risk for EONS in term and late preterm pregnancies. Methods This case–control study enrolled subjects from three maternity hospitals in Edmonton. Cases were neonates with EONS who were born at ≥ 34 weeks between January 1, 2000, and March 1, 2011. Two control subjects were enrolled for each case identified. Control subjects were neonates of similar gestation (≥ 34 weeks), born at the same hospital site, who did not develop EONS. Maternal charts were accessed for information about fetal scalp electrode application and potential confounding variables. Results Forty cases and 80 control subjects were identified. There was no difference in the rate of exposure to fetal scalp electrode in cases (6/40) and control subjects (10/80) (OR 1.24; 95% CI 0.42 to 3.68, P=0.92). The association between fetal scalp electrode application and EONS remained non-significant despite adjustment for confounders. Conclusion We did not detect an association between the use of fetal scalp electrode and EONS, but our study was powered to detect only a strong association between the exposure of interest and the disease outcome. We cannot rule out a weakly positive association that may still exist.

Oxidative stress in sperm biology - a review.

Abstract: Oxidative stress occurs when the production of potentially destructive reactive oxygen species (ROS) exceeds the bodies own naturalantioxidant defenses, resulting in cellular damage. ROS, defined as including oxygen ions, free radicals and peroxides, are generated by sperm and seminal leukocytes within semen and produce infertility by two key mechanisms.First, they damage the sperm membrane, decreasing sperm motility and its ability to fuse with the oocyte. Second, ROS can alter the sperm DNA, resulting in the passage of defective paternal DNA on to the conceptus. Spermatozoa, like all cells living in aerobic conditions face the oxygen (O2) paradox: O2 is required to support life, but its metabolites such as ROS can modify sperm cell functions, endanger sperm cell survival. ROS in small amount is necessary to maintain normal spermatozoa function. It is not surprising that a battery of different antioxidants is available to protect spermatozoa against oxidants. Spermatozoa are particularly susceptible to oxidative stress induced damage because their plasma membranes contain large quantities of polyunsaturated fatty acids (PUFA) and their cytoplasm contains low concentrations of scavenging enzymes. In addition, the intracellular antioxidant enzymes cannot protect the plasma membrane that surrounds the acrosome and the tail, forcing spermatozoa to supplement their limited intrinsic antioxidant defenses by depending on the protection afforded by the seminal plasma. Oxidative stress attacks not only the fluidity of the sperm plasma membrane, but also the integrity of DNA in the sperm nucleus. High content of polyunsaturated fatty acids in the plasma membrane and a low level of antioxidant in the sperm cytoplasm make them susceptible to oxidative stress and peroxidative attack during preservation. Defective and dead spermatozoa, major source of ROS during cryopreservation Cryoprotective media with antioxidants to overcome cryodamage.

The role of mental distraction on the pain response in healthy young Indian adults.

Abstract: Background and Objectives: The pain sensitivity of a person depends on the type of pain, his/her genetics, racial and cultural factors. Its dependence on the gender is debatable. The significance of the psychological or the behavioural intervention in pain management is gaining importance, along with a reduction in the doses of the analgesics. We wished to investigate (a) whether Indian subjects showed a pain response which was similar to that which was reported for American subjects, (b) whether sex-related differences in the pain response were present in the Indian population, and (c) which method of mental distraction (from a choice of the presence of a male/female attendant, preferred music, and solving simple arithmetic problems) was best suited for the Indian subjects. Methods: The cold pressor task was performed on a group of 80 subjects (38 females who were in the proliferative or the secretory phase of the menstrual cycle) under the conditions which have been mentioned above, as well as in the absence of mental distractants. Results: The female subjects endured pain for a longer duration while they listened to the music of their choice; the male subjects endured pain longer while they were in conversation with the female attendants. Interpretation and Conclusions: A comparison with the reported data showed the Indian males to be more pain-sensitive than the American males. Sex related differences in the pain sensitivity were absent in the Northern Indian subjects. Preferred music was the most effective mental distractant for females, while a conversation with the female attendants was the most effective distractant for the male subjects.

Accounting of ligand–receptor interactions to explore and design novel architecture for PTP 1B inhibition: a legitimate approach

Abstract: Computer-aided drug design was performed on a diverse set of 103 biphenyl derivatives that demonstrated antidiabetic activity by restraining the protein tyrosine phosphatase 1B (PTP 1B) receptor. A four-point pharmacophore hypothesis using the PHASE module of Schrodinger suite with one hydrogen bond acceptor (A) and three aromatic rings (R) as pharmacophoric features was generated. The hypothesis, ARRR.2, considered the best hypothesis in the present study is characterized by survival score (3.553), cross-validated r2 (Q2) (0.722), regression coefficient (0.949), Pearson R (0.867), and F value (492.6). The developed pharmacophore model was externally validated by predicting the activity of test set molecules. Docking algorithm combined with the drug–receptor binding free energetic and pharmacokinetic drug profile envisaged a novel concept, which may provide structural insights for the development of potential PTP 1B inhibitors. The study also provided a valid rapport between pharmacophore drug mapping, atom-based three-dimensional quantitative structure–activity relationship, molecular docking, sitemap, molecular simulations, and pharmacokinetic prediction approaches demonstrating the trends in activity. The results of these ligand–receptor relationship studies may account to design a legitimate template for the development and optimization of highly selective and potent PTP 1B inhibitors. Copyright © 2012 John Wiley & Sons, Ltd.

In silico predicative studies for cytotoxic potential of NSAIDs using self-organizing molecular field analysis.

Abstract: Antiproliferative potential of nonsteroidal anti-inflammatory drugs (NSAIDs) has generated an immense interest among the scientific fraternity to assess its broader role in the chemoprevention of colon cancer. Due to serious adverse events associated with the chemotherapy, NSAIDs have been exploited as adjuvants to synergize the cytotoxic potential of conventional chemotherapeutic agents at low-dose regimens. The present investigation has been focused on in silico model generation for in vitro cytotoxicity activity of the clinically active NSAIDs using self-organizing molecular field analysis (SOMFA) studies. A statistically validated robust model for a diverse group of NSAIDs having flexibility in structure and cytotoxicity activity was obtained using SOMFA. The statistical measures having good cross-validated correlation coefficient r (2) (cv) (.8291), noncross-validated correlation coefficient r (2) values (.8686), and high F test value (41.8722) proved significance in the generated model. Analysis of 3-dimensional quantitative structure activity relationship (3D-QSAR) models through electrostatic and shape grids provided additional valuable information regarding shape and electrostatic potential influence on in vitro cytotoxicity profile. The analysis of SOMFA results provided a better insight about the generation of molecular architecture of novel NSAIDs yet to be synthesized, with optimum in vitro cytotoxicity activity and improved therapeutic profile.