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Koel Chaudhury, Vishu Kumar, Jayaprakash Kandasamy, Sourav RoyChoudhurySchool of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, IndiaAbstract: Nanotechnology has considerably accelerated the growth of regenerative medicine in recent years. Application of nanotechnology in regenerative medicine has revolutionized the designing of grafts and scaffolds which has resulted in new grafts/scaffold systems having significantly enhanced cellular and tissue regenerative properties. Since the cell–cell and cell-matrix interaction in biological systems takes place at the nanoscale level, the application of nanotechnology gives an edge in modifying the cellular function and/or matrix function in a more desired way to mimic the native tissue/organ. In this review, we focus on the nanotechnology-based recent advances and trends in regenerative medicine and discussed under individual organ systems including bone, cartilage, nerve, skin, teeth, myocardium, liver and eye. Recent studies that are related to the design of various types of nanostructured scaffolds and incorporation of nanomaterials into the matrices are reported. We have also documented reports where these materials and matrices have been compared for their better biocompatibility and efficacy in supporting the damaged tissue. In addition to the recent developments, future directions and possible challenges in translating the findings from bench to bedside are outlined.Keywords: regenerative medicine, nanomedicine, nanotechnology

BACKGROUND/PURPOSE: The purpose of this prospective study was to review the operative findings, treatment strategies, as well as the results of management of 46 consecutive cases of jejunoileal and colonic atresia, managed over a 2-year period. MATERIALS AND METHODS: There were 42 patients with jejunoileal atresia (JIA) and 4 with colonic atresia (CA). The 4 group types were: type I-membranous (n=20), type II- blind ends separated by a fibrous cord (n=6), type IIIa- blind ends with a V-shaped mesenteric defect (n=10), type IIIb- apple-peel atresia (n=4) and type IV- multiple atresias (n=6). Primary surgery for JIA consisted of resection with a single anastomosis (n=37), anastomosis after tapering jejunoplasty (n=3), multiple anastomosis (n=1) and a Bishop-Koop ileostomy (n=1). For CA, resection with primary anastomosis was performed. A single end-to-oblique anastomosis after adequate resection of dilated proximal bowel, was the preferred surgical procedure. In the absence of facilities for administering TPN, early oral/nasogastric (NG) tube feeding was encouraged. In patients with anastomotic dysfunction, conservative treatment of the obstruction followed after its resolution by gradually increased NG feeds, was the preferred treatment protocol. RESULTS: Late presentation or diagnosis with hypovolemia, electrolyte imbalance, unconjugated hyperbilirubinemia (n=25) and sepsis (n=6), were significant preoperative findings. After resection and anastomosis, significant shortening of bowel length was seen in 16 patients (34.7%). Postoperative complications included an anastomotic leak (n=3), a perforation proximal to the anastomosis in 1 and anastomotic dysfunction in 5 patients. Full oral or NG tube feeding was possible only by the 13th to 31st postoperative day (POD), after the primary surgery in patients with anastomotic dysfunction and those undergoing reoperation. Overall, 38 patients survived (82.6%). Mortality was highest in patients with type IIIb or type IV JIA. CONCLUSIONS: Despite lack of ideal facilities for neonatal intensive care and administration of TPN, good results were achieved in the management of JIA and CA by following these principles: (1) adequate preoperative resuscitation, (2) meticulous surgical technique and a standardized surgical protocol, (3) early recognition of postoperative complications and their management by a uniform protocol and (4) wherever possible, early institution of oral or NG feeds, preferably by breast milk.

Accurate simulation of electronic excitations and deexcitations are critical for complementing complex spectroscopic experiments and can provide validation to theoretical approaches. Using a generalized framework, we contrast the accuracy and validity of orbital-constrained and linear-response approaches that build upon Kohn-Sham density functional theory (DFT) to simulate emission spectra of electronic origin and propose an efficient approximation, named many-body x-ray emission spectroscopy or MBXES, for simulating such processes. We show analytically as well as with computed examples that for electronic (de)excitation leading to an appreciable change in polarization (i.e., density rearrangement), the adiabatic approximation in a response-based formalism will be inadequate for the calculation of oscillator strength. Thus, such a change (e.g., in the net electrostatic dipole moment of a finite system) can be used as a metric for evaluating the applicability of the adiabatic response-based approach and can be particularly valuable in x-ray emission spectroscopy. On the other hand, MBXES, the flexible method introduced in this paper, can compute oscillator strengths accurately at a much lower computational expense on the basis of two DFT-based self-consistent field calculations. Using illustrative examples of emission spectra, the efficacy of the MBXES method is demonstrated by comparison with its parent theory, orbital-optimized DFT, and with experiments.

Background: Genetic instability of chromosome 11 is a frequent event in many solid tumours, including head and neck squamous cell carcinoma (HNSCC). Aims: To perform allelic imbalance analysis of cytogenetically [...]

A staged combustor concept for reducing pollutant emissions is currently under investigation. A numerical study was performed to investigate the chemically reactive flow with liquid spray injection for staged combustion. The staged combustor consists of an airblast atomizer fuel injector, a rich burn section, a converging connecting pipe, a quick mix zone, a diverging connecting pipe and a lean combustion zone. For computational efficiency, the combustor was split into two subsystems, i.e., the fuel nozzle/rich burn section and the quick mix/lean burn section. The current study investigates the effect of varying the mass flow rate split between the swirler passages for an equivalence ratio of 2.0 on fuel distribution, temperature distribution, and emissions for the fuel nozzle/rich burn section of a staged combustor. It is seen that optimizing these parameters can substantially improve combustor performance and reduce combustor emissions. The optimal mass flow rate split for reducing NOx emissions based on the numerical study was the same as found by experiment.

The aim of this in vitro study was to examine the dose-dependent effects of iron as a potential endocrine disruptor in relation to the release of sexual steroid hormones by a human adrenocortical carcinoma (NCI-H295R) cell line. The cells were exposed to different concentrations (3.90, 62.50, 250, 500, 1000 μM) of FeSO4.7H2O and compared with the control group (culture medium without FeSO4.7H2O). Cell viability was measured by the metabolic activity assay. Quantification of sexual steroid production was performed by enzyme-linked immunosorbent assay. Following 48 h culture of the cells in the presence of FeSO4.7H2O, significantly (P < 0.001) increased production of progesterone was observed at the lowest concentration (3.90 μM) of FeSO4.7H2O, whereas the lowest release of progesterone by NCIH295R cells was noted after addition of 1000 μM of FeSO4.7H2O, which did not elicit cytotoxic action (P > 0.05). Testosterone production was substantially increased at the concentrations ≤ 62.50 μM of FeSO4.7H2O. Lower levels of testosterone were recorded in the groups with higher concentrations (≥ 250 μM) of FeSO4.7H2O (P > 0.05). The presented data suggest that iron has no endocrine disruptive effect on the release of sexual steroid hormones, but its toxicity may be reflected at other points of the steroidogenesis pathway. [ABSTRACT FROM AUTHOR]

This study aimed at investigating the protective role of CoQ10 against cadmium (Cd)-induced reproductive toxicity in male rats. Adult male Wistar rats were exposed to an acute dose of Cd (25 mg/kg bwt; Cd group), Cd+CoQ10 (25 mg/kg bwt Cd+10 mg CoQ10; Cd-Q10 group) and distilled water (control) in vivo for 15 consecutive days and semen quality was assessed. A significant reduction was noted in sperm concentration, progressive motility, morphology and DNA integrity in both Cdand Cd-Q10 groups in comparison to control indicating Cd-induced testicular lipid per oxidation (LPO) and decline in indigenous antioxidant defense system as measured by total antioxidant capacity (TAC) (p<0.05). However, simultaneous co-administration of CoQ10 along with Cd (Cd-Q10 group) was able to improve sperm concentration, motility, progressive motility, morphology, DNA integrity, and testicular TAC as well as lower LPO compared to Cd group (p<0.05). Results indicate that used dose of CoQ10 is capable of moderately ameliorating reproductive toxicity of Cd by improving semen quality and reducing testicular oxidative stress. [ABSTRACT FROM AUTHOR]

Summary: Polyvinylpyrrolidone (PVP) and hyaluronic acid (HA) are routinely used in handling spermatozoa for intracytoplasmic sperm injection (ICSI). As there are still concerns about possible adverse effects on the embryo, this study investigated sperm handling in a mouse ICSI model to (i) evaluate oocyte activation after injection of spermatozoa selected for rotational or linear motion in PVP; (ii) assess the effect of sperm selection in PVP, HA and medium on oocyte activation; (iii) examine the effects of PVP and HA on parthenogenetic oocyte activation and embryo development; and (iv) assess the oxidation–reduction potential (ORP) of spermatozoa exposed to PVP, HA or medium. Oocyte activation was higher when spermatozoa exhibited rotational motion rather than linear motion (79% vs. 52%; p = .05). There was no difference in oocyte activation and embryo development after parthenogenetic oocyte activation after sperm injection using PVP, HA or medium‐incubated spermatozoa. PVP‐selected spermatozoa exhibited lower (p < .0001) ORP levels than using HA. Thus, results indicate that the sperm handling method and the type of medium used impact ICSI outcomes. Overall, sperm incubation in PVP, HA and medium yields similar outcomes with regard to oocyte activation and embryo development. However, PVP provides more antioxidative protection than HA and should therefore be preferred for sperm manipulation. [ABSTRACT FROM AUTHOR]

Summary: Oxidation–reduction potential (ORP) is a newer integrated measure of the balance between total oxidants (reactive oxygen species—ROS) and reductants (antioxidants) that reflects oxidative stress in a biological system. This study measures ORP and evaluates the effect of exogenous induction of oxidative stress by cumene hydroperoxide (CH) on ORP in fresh and frozen semen using the MiOXSYS Analyzer. Semen samples from healthy donors (n = 20) were collected and evaluated for sperm parameters. All samples were then flash‐frozen at −80°C. Oxidative stress was induced by CH (5 and 50 μmoles/ml). Static ORP (sORP—(mV/106 sperm/ml) and capacity ORP (cORP—μC/106 sperm/ml) were measured in all samples before and after freezing. All values are reported as mean ± SEM. Both 5 and 50 μmoles/ml of CH resulted in a significant decline in per cent motility compared to control in pre‐freeze semen samples. The increase in both pre‐freeze and post‐thaw semen samples for sORP was higher in the controls than with 50 μmoles/ml of CH. The change from pre‐freeze to post‐thaw cORP was comparable. The system is a simple, sensitive and portable tool to measure the seminal ORP and its dynamic impact on sperm parameters in both fresh and frozen semen specimens. [ABSTRACT FROM AUTHOR]

The goal of this study is to summarize the current knowledge on the effects of one of the essential metals, copper (Cu) on the reproductive system. The development of past four decades addressing effects of Cu on reproductive organs is reviewed. The most relevant data obtained from in vivo and in vitro experiments performed on humans and other mammals, including effects of copper nanoparticles (CuNPs) on the reproductive functions are presented. Short term Cu administration has been found to exert deleterious effect on intracellular organelles of rat ovarian cells in vivo. In vitro administration in porcine ovarian granulosa cells releases insulin-like growth factor (IGF-I), steroid hormone progesterone (P4), and induces expression of peptides related to proliferation and apoptosis. Adverse effect of Cu on male reproductive functions has been indicated by the decrease in spermatozoa parameters such as concentration, viability and motility. Copper nanoparticles are capable of generating oxidative stress in vitro thereby leading to reproductive toxicity. Toxic effect of CuNPs has been evident more in male mice than in females. Even though further investigations are necessary to arrive at a definitive conclusion, Cu notably influences the reproductive functions by interfering with both male and female reproductive systems and also hampers embryo development in dose-dependent manner. [ABSTRACT FROM AUTHOR]

Protein kinases, transcription factors and other apoptosis- and proliferation-related proteins can regulate reproduction, but their involvement in sexual maturation remains to be elucidated. The general aim of the in vivo and in vitro experiments with porcine ovarian granulosa cells was to identify possible intracellular regulators of female sexual maturation. For this purpose, proliferation (expression of proliferating cell nuclear antigen – PCNA, mitogen-activated protein kinases – ERK 1,2 related MAPK and cyclin B1), apoptosis (expression of the apoptotic protein Bax and apoptosis regulator Bcl-2 protein), expression of some protein kinases (cAMP dependent protein kinase – PKA, cGMPdependent protein kinase – PKG, tyrosine kinase – TK) and cAMP responsive element binding protein 1 (CREB-1) was examined in granulosa cells isolated from ovaries of immature and mature gilts. Expression of PCNA, ERK1,2 related MAPK, cyclin B1, Bcl-2, Bax, PKA, CREB-1, TK and PKG in porcine granulosa cells were detected by immunocytochemistry. Sexual maturation was associated with significant increase in the expression of Bcl-2, Bax, PKA, CREB-1 and TK and with decrease in the expression of ERK1,2 related MAPK, cyclin B1 and PKG in granulosa cells. No significant difference in PCNA expression was noted. The present data obtained from in vitro study indicate that sexual maturation in females is influenced by puberty-related changes in porcine ovarian signaling substances: increase in Bcl-2, Bax, PKA, CREB-1, TK and decrease in ERK1,2 related MAPK, cyclin B1 and PKG. It suggests that these signaling molecules could be potential regulators of porcine sexual maturation. [ABSTRACT FROM AUTHOR]

This study aimed at examining the secretion activity of steroid hormones progesterone and 17ß-estradiol by porcine ovarian granulosa cells after addition of green tea extract. Granulosa cells were incubated with green tea extract (at doses of 0.01, 0.1, 1, 10 and 100 μg.ml-1). Another set of cells were incubated with green tea extract at the above doses along with additional supplementation of follicle stimulating hormone (FSH) at 10 μg.ml-1. Release of hormones by granulosa cells was assessed by EIA after 24 h exposure. Secretion of steroid hormones was not affected either by green tea extract alone or after FSH supplementation with green tea extract. Results indicate that ovarian steroidogenesis is not affected by green tea under conditions used in the experiment. [ABSTRACT FROM AUTHOR]

The spindle assembly checkpoint (SAC) is a 'wait-anaphase' mechanism that has evolved in eukaryotic cells in response to the stochastic nature of chromosome-spindle attachments. In the recent past, different aspects of the SAC regulation have been described. However, the role of microRNAs in the SAC is vaguely understood. We report here that Mad1, a core SAC protein, is repressed by human miR-125b. Mad1 serves as an adaptor protein for Mad2 - which functions to inhibit anaphase entry till the chromosomal defects in metaphase are corrected. We show that exogenous expression of miR-125b, through downregulation of Mad1, delays cells at metaphase. As a result of this delay, cells proceed towards apoptotic death, which follows from elevated chromosomal abnormalities upon ectopic expression of miR-125b. Moreover, expressions of Mad1 and miR-125b are inversely correlated in a variety of cancer cell lines, as well as in primary head and neck tumour tissues. We conclude that increased expression of miR-125b inhibits cell proliferation by suppressing Mad1 and activating the SAC transiently. We hypothesize an optimum Mad1 level and thus, a properly scheduled SAC is maintained partly by miR-125b. [ABSTRACT FROM AUTHOR]

PURPOSE: To present a retrospective analysis of 10 cases of osteochondroma of the mandibular condyle (operated between 1993 and 2009) with respect to age, gender, site of the pathology, treatment modality and recurrence, with review of literature. MATERIALS AND METHODS: Medical records with x-rays, computed tomography scans, and bone scans of all histologically proven osteochondroma of mandibular condyle cases operated between 1993 and 2009 were retrieved and examined. The data were tabulated and analyzed. RESULTS: There were 8 males and 2 females, with a right:left ratio of 2.3:1. Age range was 18 to 45 years with a mean of 29.4 years. Seven of 10 were superomedial in location. Six patients were treated by conservative condylectomy, whereas 4 required total condylectomy. In all cases, a preauricular with extended temporal approach was used. In the follow-up period ranging from 1 year to 13 years, there was no recurrence. CONCLUSION: Mandibular condylar osteochondroma is thought to be a relatively rare lesion with only 90 cases documented in the English language literature to date. Gradual facial asymmetry over the years is the most striking feature. Two types are identified: those causing growth potential in mandible causing bowing of ipsilateral body and requiring gnathic correction after excision of tumor, and others growing as tumors superior or superomedial to condyle without causing much growth in the mandible, requiring only excision and automatic swing back to correct asymmetry. Both the procedures---conservative condylectomy and the total condylectomy---are curative. The decision, however, depends on how much swing of mandible is required postsurgery for correction of asymmetry and occlusion. [ABSTRACT FROM AUTHOR]

To improve mulberry foliage productivity, identification of suitable genes related to agronomically important traits in the available mulberry germplasm is essential. Twenty-five indigenous mulberry accessions representing five different species of Morus from seven diverse parts of the India were evaluated via principal component analysis (PCA) for 22 aboveground and underground morphometric traits and silkworm cocoon yield during 2002–2005 in the agro-climates of Berhampore, West Bengal, India. Significant differences among germplasm accessions were observed for all 22 traits and cocoon yield. Six principal components were identified, which explained >88% of total variation. Though 18 major variables were included in the principal components, longest shoot length, leaf area, intermodal distance, green and dry leaf weight, lamina length, lamina weight, root volume, and fresh and dry root weight were recognized as important variables that had direct effect on silkworm cocoon yield. These 10 variables appeared to be minimal traits for quick selection of mulberry progenies in breeding programs. Four distinct groups of accessions obtained after a cluster analysis were partly associated with their places of origin. In addition, the study highlighted a number of distinctive morphological characters in many of the accessions studied. The identified 10 minimum morphological descriptors were expected to be highly discriminating, thus they would help in quick characterization of mulberry germplasm. In addition, the distantly related germplasm were identified on the basis of cluster analysis and can be utilized in targeted mulberry improvement programs. [ABSTRACT FROM PUBLISHER]

Benzene exposure from vehicular sources and its health impact are relatively unexplored in India. We have investigated in this study hematology and lymphocyte subsets of 25 petrol pump attendants, 25 automobile service station workers and 35 controls matched for age, sex and socioeconomic conditions. The participants were non-smoking males of Kolkata (former Calcutta) in eastern India. Compared with controls, the workers had 3.8- times more trans,trans-muconic acid in urine, suggesting higher level of benzene exposure. The exposed subjects had decreased erythrocyte, hemoglobin, lymphocyte and platelet levels, but increased neutrophil, band cells, RBC aniso-poikilocytosis and target cells. In addition, CD4+, CD8+ and CD19+ cells were decreased by 37, 20 and 47% respectively, but CD 16+ 56+ NK cells were increased by 20%. P-selectin expression on platelet surface of the workers was significantly elevated (P < 0.05), indicating upregulation of platelet activity. In summary, the study revealed high level of benzene exposure from vehicular sources in India, and the exposed subjects had hematological and immunological alterations. [ABSTRACT FROM AUTHOR]

The homogeneously staining region (hsr) involving chromosome band 11q13 includes amplified genes from this chromosome segment and carries a relatively poor prognosis in oral squamous cell carcinomas (OSCC), with shorter time to recurrence and reduced overall survival. We previously identified an inverted duplication pattern of genes within the 11q13 hsr in OSCC cells, supporting a breakage-fusion-bridge (BFB) cycle model for gene amplification. To validate our hypothesis that 11q13 gene amplification in OSCC occurs via BFB cycles, we carried out fluorescence in situ hybridization (FISH) using probes for band 11q13 on 29 OSCC cell lines. We demonstrate that all OSCC cell lines with 11q13 amplification express a significantly higher frequency of anaphase bridges containing 11q13 sequences compared to cell lines without amplification, providing further experimental evidence that 11q13 gene amplification in OSCC cells occurs via BFB cycles. Elucidation of mechanisms responsible for initiating and promoting gene amplification provides opportunities to identify new biomarkers to aid in the diagnosis and prognosis of oral cancer, and may be useful for developing novel therapeutic strategies for patients with OSCC. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The majority of households in rural India still rely on unprocessed solid biomass for domestic energy. The aim of this study was to investigate whether chronic exposure to biomass smoke causes activation of leukocytes and the formation of leukocyte–platelet aggregates. We conducted flow cytometric analysis of β2 Mac-1 integrin (CD11b/CD18) expression on polymorphonuclear leukocytes (PMN) and monocytes, and P-selectin (CD62P) expression on the platelets of 165 women from eastern India, who cook solely with wood, dung and agricultural wastes, and 155 age- and socio-economic condition-matched control subjects, who used relatively cleaner fuel, liquefied petroleum gas (LPG). Leukocyte-platelet aggregates were defined as CD11b-positive PMN and monocytes co-expressing platelet-specific markers CD41 or CD62P. A significant increase in leukocyte–platelet aggregates was found in women who used biomass as cooking fuel. In addition, they showed increased surface expression of CD11b/CD18 in circulating PMN and monocytes and CD62P expression on platelets. The mean fluorescence intensity (MFI) of CD11b on the surface of circulating monocytes and PMN of biomass users increased by 50 and 68%, respectively. Similarly, a 62 and 48% increase in MFI was observed in CD18 expression on the surface of these cells in biomass users. The results show that chronic biomass smoke exposure activates circulating platelets, PMN and monocytes, and increases the number of leukocyte–platelet aggregates, which are considered a risk factor for thrombosis. [ABSTRACT FROM AUTHOR]

Background: Genetic instability of chromosome 11 is a frequent event in many solid tumours, including head and neck squamous cell carcinoma (HNSCC). Aims: To perform allelic imbalance analysis of cytogenetically mapped altered regions of human chromosome 11 in patients with HNSCC from eastern India. Methods: Genomic alterations were investigated using highly polymorphic microsatellite markers in both HNSCC and leukoplakia tissues. Results: Microsatellite markers D11S1758 from 11p13-15 and D11S925 from 11q23.3-24 had the highest frequency (38% and 32%, respectively) of loss of heterozygosity among all the markers analysed. Allelic loss at the marker D11S925 was seen in both leukoplakia and in all stages of HNSCC tumour tissues suggesting that it is an early event in HNSCC tumorigenesis. Microsatellite size alteration was also found to be high (> 20%) in several markers. In leukoplakia samples microsatellite instability was seen at a higher frequency than loss of the allele, indicating such alterations might initiate the process of tumorigenesis in HNSCC. Conclusions: The high rate of chromosomal alterations at 11q21-24 in HNSCC suggests the presence of a putative tumour suppressor gene in this region. [ABSTRACT FROM AUTHOR]

It has been proposed that a constellation of three TP53 polymorphisms (intron 3 16 bp duplication, codon 72 BstUI, and intron 6 Nci I RFLP at nt 13494) constitute a haplotype predictive of increased cancer risk. We have estimated the allele frequency of these polymorphisms in three endogamous Indian ethnic populations from three different geographic locations (viz. Iyer from south India, Brahmin from central India and Mahishya from eastern India), as well as in head and neck squamous cell carcinoma (HNSCC) patients, and in ethnically matched normal individuals from the eastern region of India. The genotype distributions and allele frequencies of the three polymorphisms in all but one population, as well as in patients, showed a good fit to Hardy-Weinberg equilibrium. Strong linkage disequilibria were observed between all loci in every population examined, except for the 16bp-NciI haplotype in the Mahishya population. The Mahishya population differed significantly from the other two populations with respect to differences in allele frequency and haplotype frequency. Although there were no significant differences in genotypic frequency at any of the loci between HNSCC patients and the matched control population, the minor allele frequency of codon 72 and intron 3 16 bp polymorphisms showed significant variation. Variation in overall haplotype frequency between patients and normal individuals was significant (p = 0.036) when two rare haplotypes 2-1-2 and 1-2-1 were combined. The rare haplotype 2-1-2 was found to be modestly over represented in HNSCC patients as compared to normal individuals. [ABSTRACT FROM AUTHOR]

One of the approaches investigated for multihop lightwave networks is to consider regular graphs as the logical topology for a multihop network. Standard regular topologies are defined only for networks with the number of nodes satisfying some rigid criteria and are not directly usable for multihop networks. Only a few recent proposals (e.g., GEMNET) are regular and yet allow the number of nodes to have any arbitrary value. These networks have one major problem — node addition requires a major redefinition of the network. For example, in a multistar implementation, a large number of retuning of transmitters and receivers and/or renumbering nodes are needed for GEMNET. In this paper we present a new logical topology which has a low diameter but is not strictly regular. The interesting aspect of this topology is that it allows the network to be expanded incrementally involving a relatively small number of edge definitions/redefinitions. In this paper we have described our new topology and its properties. We have also implemented a routing scheme that ensures a low diameter and an algorithm for adding nodes to the network. [ABSTRACT FROM AUTHOR]

The newly developed 8-methoxy, non-fluorinated quinolones (NFQs) were studied to elucidate their enzyme inhibitory activity against wild-type and mutant GyrA (Ser-83-->Trp) forms of Escherichia coli DNA gyrase. Using a DNA supercoiling inhibition assay, the NFQs were found to inhibit 50% (IC50) of the E. coli DNA gyrase activity in the 1.6-3.2 mg/L concentration range and were comparable to ciprofloxacin. However, against the GyrA (Ser-83-->Trp) mutant, the NFQs were approximately 16-fold more potent than ciprofloxacin. Antibacterial potency of the NFQs was investigated using clinical isolates of E. coli and penicillin-resistant Streptococcus pneumoniae (PRSP), including strains with reduced susceptibility to quinolones. Against 20 uncharacterized clinical isolates of E. coli, the MIC90s of the NFQs were in the 0.125-0.25 mg/L range while those of ciprofloxacin, trovafloxacin, gatifloxacin and clinafloxacin were in the 0.016-0.125 mg/L range. Against clinical isolates with characterized mutations in gyrA and parC, PGE9262932, an NFQ, was two- to eight-fold more potent than ciprofloxacin. Against 23 clinical isolates of PRSP, the NFQs (MIC90 0.031-0.125 mg/L) were more potent than ciprofloxacin, trovafloxacin, and gatifloxacin (MIC90 0.25-2.0 mg/L), and at least as potent as clinafloxacin (MIC90 0.125 mg/L). Against S. pneumoniae strains with gyrA and parC mutations, the NFQs (MIC 0.125-1.0 mg/L) were more potent than ciprofloxacin, trovafloxacin and gatifloxacin (MIC 4-32 mg/L), and comparable to clinafloxacin (MIC 0.5-1 mg/L). [ABSTRACT FROM AUTHOR]

The aim of this in vitro study was to examine the secretion activity (progesterone, 17β-estradiol and insulin-like growth factor-I) of rat ovarian fragments after molybdenum (Mo) addition. Rat ovarian fragments were incubated with ammonium molybdate (NH4)6MO7O24.4H2O at the doses 90, 170, 330 and 500 ug.ml1 for 24 h and compared with control group without Mo addition. Release of progesterone (P4), estradiol (17β-estradiol) and insulin-like growth factor I (IGF-I) by ovarian fragments was assessed by radioimmunoassay (RIA). Data show that P4 release by ovarian fragments was not affected by (NH4)6Mo7O24.4H2O addition at all the doses used (90-500 µg.ml-1). However, addition of ammonium molybdate was found to cause a significant (P<0.05) dose-dependent decrease (at the doses 90, 170 and 500 ug.ml1) in release of 17β-estradiol by ovarian fragments in comparison to control. Also, addition of ammonium molybdate significantly (P<0.05) inhibited IGF-I release at all the doses (90-500 µg.ml-1) used in the study. Results suggest ammonium molybdate induced inhibition in the release of growth factor IGF-I and its dose-dependent effect on secretion of steroid hormone 17β-estradiol but not progesterone. These data contribute to new insights regarding the mechanism of action of Mo on rat ovarian functions. [ABSTRACT FROM AUTHOR]

Information on the 30th Annual Convention of the Indian Association for Cancer (IACR) and the International Symposium on 'Signaling Network in Cancer," that was held in Kolkata, India from February 6 to 9, 2011 is presented. The meeting several lectures on cell cycle, cell death, cancer immunology and genetics were presented. The symposium was attended by several scientists across the world, including Mark Meuth, K. Somasundaram and W.S. El-Deiry.

Abstract Introduction To understand the role of two interacting proteins LIMD1 and pRB in development of head and neck squamous cell carcinoma (HNSCC), alterations of these genes were analyzed in 25 dysplastic head and neck lesions, 58 primary HNSCC samples and two HNSCC cell lines. Methods Deletions of LIMD1 and RB1 were analyzed along with mutation and promoter methylation analysis of LIMD1. The genotyping of LIMD1 linked microsatellite marker, hmlimD1, was done to find out any risk allele. The mRNA expression of LIMD1 and RB1 were analyzed by Q-PCR. Immunohistochemical analysis of RB1 was performed. Alterations of these genes were correlated with different clinicopathological parameters. Results High frequency [94% (78/83)] of LIMD1 alterations was observed in the samples studied. Compare to frequent deletion and methylation, mutation of LIMD1 was increased during tumor progression (P = 0.007). Six novel mutations in exon1 and one novel intron4/exon5 splice-junction mutation were detected in LIMD1 along with a susceptible hmlimD1 (CA)20 allele. Some of these mutations [42% (14/33)] produced non-functional proteins. RB1 deletion was infrequent (27%). Highly reduced mRNA expression of LIMD1 (25.1 ± 19.04) was seen than RB1 (3.8 ± 8.09), concordant to their molecular alterations. The pRB expression supported this data. Tumors with LIMD1 alterations in tobacco addicted patients without HPV infection showed poor prognosis. Co-alterations of these genes led the worse patients' outcome. Conclusions Our study suggests LIMD1 inactivation as primary event than inactivation of RB1 in HNSCC development.