Assessment of antibacterial efficacy of a biocompatible nanoparticle PC@AgNPs against Staphylococcus aureus.

A plant, Priva cordifolia mediated silver nanoparticle was prepared and characterized by UV-Vis spectroscopy, fourier-transform infrared spectroscopy (FT-IR), energy dispersive X-ray (EDX), scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS) and x-ray diffraction (XRD) analysis. The minimum inhibitory concentration of the synthesized nanoparticle against Staphylococcus aureus was found to be 100 ±â€¯0.80 µg/mL with 9.38 ±â€¯0.04 mm zone of inhibition. The bactericidal activity was shown primarily due to membrane damage evident from SEM, atomic force microscopy (AFM), potassium efflux, cellular material leakage, and bio-electrochemical changes in electron transport chain data. It was also of interest to find PC@AgNPs interfering with biofilm formation by S.aureus, assessed qualitatively by SEM, confocal laser scanning microscopy (CLSM) and quantitatively by dye staining method. The bio-compatibility of PC@AgNPs was established by anti-coagulant, thrombolytic, partial thromboplastin time, thrombin-like activity and fibrinolytic activity that suggested its good maintenance of hemostatic conditions. PC@AgNPs also prevented the coagulation of rabbit plasma which as per the standard drug Dabigatran reaction was indicative of the down-regulation of virulence Coa gene expression.

Synthesis of novel benzodioxane midst piperazine moiety decorated chitosan silver nanoparticle against biohazard pathogens and as potential anti-inflammatory candidate: A molecular docking studies.

Nanoparticles (NPs) are currently being investigated along with the use of biodegradable polymer containing active agents in many areas of medicine for targeted applications. The present study was aimed to synthesize novel compound Benzodioxane midst piperazine (BP) and characterization of a BP decorated chitosan silver nanoparticles (BP*C@AgNPs) and shown effective against hazardous pathogens, and also having anti-inflammatory property. It was further evaluated for molecular docking proofs, and toxicity. The BP*C@AgNPs had spherical shape with size of 36.6nm with wide biocidal activity against hazardous Gram-positive and Gram-negative bacteria with excellent inhibition at 100µg/mL for S. aureus (10.08±0.05mm ZOI), and E. coli (10.03±0.04mm ZOI) compared to antibiotic Streptomycin. The anti-inflammatory activity exhibited IC50 value of 71.61±1.05µg/mL for BP*C@AgNPs compared to indomethacin (IC50=40.15±1.21µg/mL). Also, the docking study of BP showed excellent score for COX1 and DNA gyrase. This in silico study confirmed the achieved efficacy of BP, with less toxicity against normal PMBCs in vitro and in vivo studies. This study concludes that, the novel synthesized BP*C@AgNPs had excellent biocidal property and as anti-inflammatory candidate revealed by docking studies, it confirms BP*C@AgNPs for first-class therapeutic applications in the area of medicinal nanotechnology for the coming days.

F wave index: A diagnostic tool for peripheral neuropathy.

BACKGROUND & OBJECTIVES: Each skeletal muscle is usually supplied by two or more nerve roots and if one nerve root is affected and the other is spared, the clinically used F wave minimum latency can still be normal. An F wave index was constructed taking into consideration the other parameters of the F wave such as persistence, chronodispersion, latency, arm-length to determine its usefulness in the diagnosis of peripheral neuropathy. This study was undertaken to construct the F wave index in the upper limb for the median nerve in normal healthy adult males and in patients with peripheral neuropathy and to compare the values obtained in both groups. METHODS: This hospital-based study was carried out on 40 males who were diagnosed to have peripheral neuropathy and on 40 age matched healthy males who served as the control group. The F wave recording was done using a digitalized nerve conduction/electromyography/EP machine in a quiet and dimly lit room. All recordings were done between 0900 and 1100 h at an ambient temperature of 22°C. The F wave recording was obtained from a fully relaxed muscle by stimulating the median nerve. RESULTS: The median value for F wave index obtained from median nerve (abductor pollicis brevis) in patients with peripheral neuropathy [right arm - 35.85, interquartile range (IQR) - 35.26; left arm - 39.49, IQR - 39.49] was significantly lower (P=0.001) as compared to the control group (right arm - 102.62, IQR - 83.76; left arm - 77.43, IQR - 58.02). INTERPRETATION & CONCLUSIONS: Our results showed that F wave index in upper limb was significantly lower in patients with peripheral neuropathy than the healthy controls, and could be used for early detection of peripheral neuropathy.

Classification, Source, and Effect of Environmental Pollutants and Their Biodegradation.

Any foreign chemical substance that is unusually present within an organism or is unexpectedly found in the environment at a higher concentration than the permissible limits can be termed a xenobiotic or a pollutant. Such substances include carcinogens, drugs, food additives, hydrocarbons, dioxins, polychlorinated biphenyls, pesticides or even some natural compounds. Pollutants are known for their higher persistence and pervasiveness, and along with their transformed products, they can remain in and interact with the environment for prolonged periods. In this article, the classification of such substances based on their nature, use, physical state, pathophysiological effects, and sources is discussed. The effects of pollutants on the environment, their biotransformation in terms of bioaccumulation, and the different types of remediation such as in situ and ex situ remediation, are also presented.

Role of Altered Venous Blood Lactate and HbA1c in Women with Gestational Diabetes Mellitus.

INTRODUCTION: Being a mirror image of metabolic syndrome, Gestational Diabetes Mellitus (GDM) is associated with significant maternal and fetal morbidity. Increased blood lactate concentration and alterations of substrate utilization are partly involved in development of insulin resistance in GDM. Fetuses born to such mothers have shown low umbilical vein oxygen saturation and low oxygen content and increased lactate concentrations. These changes may certainly reflect enhanced fetal metabolism as a result of hyperglycaemia and hyperinsulinemia and therefore, these fetuses deserve intense surveillance at term and during delivery. Ideally, HbA1c should be maintained below 5% during their first trimesters and below 6% during third trimester. We planned to investigate GDM women for their HbA1c levels too. AIM: To know if there is any alteration in blood lactate and/or HbA1c levels and to know if there is any correlation between these two parameters in GDM pregnancies, in comparison with the previous studies which measured lactate in cord blood and placental vessels of GDM women. MATERIALS AND METHODS: It was a hospital based prospective study on 40 women with gestational diabetes and 40 age-matched normal pregnant women. We analysed the biochemical and metabolic mileau in these women by estimating venous blood lactate and HbA1c levels. We paid special attention to follow them up regarding maternal complications if any and perinatal outcomes. The independent samples t-test and Pearson's correlation test were applied. RESULTS: GDM mothers showed significantly higher lactate and HbA1c levels than normal pregnant women, both with p<0.001. Blood pressure and fetal birth weight were also significantly higher in GDM group than Normal Pregnant (NP) group, both with p-values of <0.001. Further, this increased lactate levels showed significant positive correlation with HbA1c, blood pressure and fetal birth weight. CONCLUSION: Maternal blood lactate and HbA1c levels have a significant role to play in determining the metabolic mileau of both mother and fetus and thus, their obstetric and general health outcomes.

Comparison of Cardiovascular Parameters and Cardiac Autonomic Activity of Obese and Normal Weight School Children in Puducherry.

Background and Aim: Worldwide, incidence of childhood obesity is on the rising trend and obese children are more vulnerable to various health disorders. This study was done to assess and compare the cardiovascular parameters and Heart rate variability (HRV) parameters of obese school children with children with normal Body Mass Index (BMI). Methods: Thirty obese children (BMI  95th percentile) aged 9-12 years and 30 age and sex matched children with normal BMI (BMI 5th to below 85th percentile) were included in test and control groups respectively. Mann Whitney U test was done to detect the difference between the two groups with respect to systolic blood pressure (SBP), diastolic blood pressure (DBP) and HRV parameters. Sub-analyses were also done to compare the data of boys of control and test groups and the data of girls of control and test groups. Results: SBP, DBP and Mean arterial pressure (MAP) were significantly high in the test group. However, there was no significant difference between test and control groups with respect to HRV parameters. Subanalyses revealed that the obese boys had a significantly high SBP, DBP, MAP, rate pressure product (RPP) and a significantly low total HRV while the obese girls had a significantly raised SDNN, RMSSD, pNN50, LF power, HF power and total HRV. Conclusion: The obese children had a significantly raised blood pressure. There was no difference in the HRV parameters of normal weight and obese children. However, obese boys had a significantly reduced total HRV when compared to normal weight boys while the obese girls had a significantly raised total HRV when compared to normal weight girls. The various physiological changes during puberty and the time of onset of puberty may have a varying impact on the cardiac autonomic status of obese male and female children.

Toxicity, mechanism and health effects of some heavy metals.

Heavy metal toxicity has proven to be a major threat and there are several health risks associated with it. The toxic effects of these metals, even though they do not have any biological role, remain present in some or the other form harmful for the human body and its proper functioning. They sometimes act as a pseudo element of the body while at certain times they may even interfere with metabolic processes. Few metals, such as aluminium, can be removed through elimination activities, while some metals get accumulated in the body and food chain, exhibiting a chronic nature. Various public health measures have been undertaken to control, prevent and treat metal toxicity occurring at various levels, such as occupational exposure, accidents and environmental factors. Metal toxicity depends upon the absorbed dose, the route of exposure and duration of exposure, i.e. acute or chronic. This can lead to various disorders and can also result in excessive damage due to oxidative stress induced by free radical formation. This review gives details about some heavy metals and their toxicity mechanisms, along with their health effects.

A comparative study of the effects of asan, pranayama and asan-pranayama training on neurological and neuromuscular functions of Pondicherry police trainees.

BACKGROUND: Though neurological benefits of yoga training have been reported, lacunae still exists in understanding neurophysiological effects of such training. Hence, the present study was conducted to find the effect of yogasanas and pranayams on neurological and neuromuscular functions in healthy human volunteers and also determined differential effects of training in asan, pranayama and their combination. MATERIALS AND METHODS: Eighty male trainees from Pondicherry Police Training School were randomly divided into asan, pranayama, and asan-pranayama groups who received a training of 4 days a week for 6 months and a control group. Electroencephalogram (EEG), nerve conduction (NC), electromyogram (EMG), visual evoked potentials (VEP), and auditory reaction time (ART) were recorded before and after the study period. NC, EMG, and VEP data were obtained from 28 subjects; EEG data from 48 subjects; and RT from 67 subjects. Intergroup differences were assessed by AVOVA/Kruskal-Wallis and intragroup differences by Student's t-test. RESULTS AND DISCUSSION: Police trainees showed beneficial effects of yoga training, although they were undergoing intensive police training and the yoga training was relatively less intense. Alpha, theta, and total power of EEG increased as a result of asan training. A shortening of visual reaction time and a decrease in red-green discriminatory reaction time signifies an improved and faster processing of visual input. They also showed a decrease in resting EMG voltage, signifying better muscular relaxation following pranayama training. Beta, theta and total power of EEG increased. ART and red-green discriminatory reaction times decreased in the trainees, signifying a more alert state as well as improved central neural processing. A combination of asan and pranayama training for 6 months produced an improvement in motor and sensory nerve conduction. Total power of EEG, alpha and theta power as well as delta % increased, while reaction time decreased signifying an alert and yet relaxed state of the neuromuscular system. SUMMARY AND CONCLUSION: The present study has shown that 6 months training in asan, pranayama as well as their combination is effective in improving physiological functions of police trainees. They showed beneficial effects of yoga training, although they were undergoing intensive police training and the yoga training was relatively less intense. Hence, we recommend that yoga training be introduced in police training curricula.

Umesh's intubation detector (UID) for rapid and reliable identification of tracheal intubation by novices in anaesthetised, paralysed adult patients.

Oesophageal intubation can lead to life threatening complications if left undetected. Several devices and techniques are available to confirm tracheal intubation and for early detection of oesophageal intubation. This study was carried out to evaluate the utility of the Umesh's intubation detector device for rapid and reliable differentiation of tracheal from oesophageal intubation by novice users. In this prospective, double blind and randomised study, 100 healthy patients undergoing general anaesthesia with endotracheal intubation received two identical size endotracheal tubes; one inserted into trachea and the other into the oesophagus. The Umesh's intubation detector was connected to one of the tubes randomly and a novice was asked to observe for inflation of the reservoir bag of the device while two chest compressions of approximately one inch each were given to the patient. Out of the total 100 tracheal intubations, 96 were correctly identified while the observers could not clearly conclude whether the tube was in trachea or oesophagus in the other four patients. Out of the total 100 oesophageal intubations, 99 were correctly identified. There were no complications related to the study. Umesh's intubation detector device can be used by novices for rapid and reliable differentiation of tracheal from oesophageal intubation in healthy adult patients.

Encapsulated cell grafts to treat cellular deficiencies and dysfunction.

Cell transplantation provides a therapeutic alternative to whole organ transplantation in the management of diseases arising from the absence or failure of specialized cells. Though allogenic transplantation is favorable in terms of graft acceptance, xenotransplantation can provide a potentially unlimited source of cells and can overcome shortage of human donors. Effective immunoisolation of the xenografts is critical for their long term survival and function. Encapsulation of cells in polymeric matrices, organic or inorganic, provides a physical selectively permeable barrier between the host and the graft, thereby immunoisolating the graft. Microencapsulation of cells in alginate hydrogels has been pervasive, but this approach does not provide precise control over porosity, whereas micro- and nano-fabrication technologies can provide precise and reproducible control over porosity. We highlight both encapsulation approaches in this review, with their relative advantages and challenges. We also highlight the therapeutic potential of encapsulated cells for treating a variety of diseases, detailing the xenotransplantation of pancreatic islets in diabetes therapy as well as the grafting of engineered cells that facilitate localized enzyme-prodrug therapy of pancreatic cancer.

Structural variation in bacterial glyoxalase I enzymes: investigation of the metalloenzyme glyoxalase I from Clostridium acetobutylicum.

The glyoxalase system catalyzes the conversion of toxic, metabolically produced α-ketoaldehydes, such as methylglyoxal, into their corresponding nontoxic 2-hydroxycarboxylic acids, leading to detoxification of these cellular metabolites. Previous studies on the first enzyme in the glyoxalase system, glyoxalase I (GlxI), from yeast, protozoa, animals, humans, plants, and Gram-negative bacteria, have suggested two metal activation classes, Zn(2+) and non-Zn(2+) activation. Here, we report a biochemical and structural investigation of the GlxI from Clostridium acetobutylicum, which is the first GlxI enzyme from Gram-positive bacteria that has been fully characterized as to its three-dimensional structure and its detailed metal specificity. It is a Ni(2+)/Co(2+)-activated enzyme, in which the active site geometry forms an octahedral coordination with one metal atom, two water molecules, and four metal-binding ligands, although its inactive Zn(2+)-bound form possesses a trigonal bipyramidal geometry with only one water molecule liganded to the metal center. This enzyme also possesses a unique dimeric molecular structure. Unlike other small homodimeric GlxI where two active sites are located at the dimeric interface, the C. acetobutylicum dimeric GlxI enzyme also forms two active sites but each within single subunits. Interestingly, even though this enzyme possesses a different dimeric structure from previously studied GlxI, its metal activation characteristics are consistent with properties of other GlxI. These findings indicate that metal activation profiles in this class of enzyme hold true across diverse quaternary structure arrangements.

The exonuclease activity of hPMC2 is required for transcriptional regulation of the QR gene and repair of estrogen-induced abasic sites.

We have previously reported that the expression of antioxidative stress enzymes is upregulated by trans-hydroxytamoxifen (TOT) in breast epithelial cell lines providing protection against estrogen-induced DNA damage. This regulation involves Estrogen Receptor ß (ERß) recruitment to the Electrophile Response Element (EpRE) and a novel protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2). We have also demonstrated that ERß and hPMC2 are required for TOT-dependent recruitment of poly (ADP-ribose) polymerase 1 (PARP-1) and Topoisomerase IIß (Topo IIß) to the EpRE. Sequence analysis reveals that the C-terminus of hPMC2 encodes a putative exonuclease domain. Using in vitro kinetic assays, we found that hPMC2 is a 3'-5' non-processive exonuclease that degrades both single-stranded and double-stranded substrates. Mutation of two conserved carboxylate residues drastically reduced the exonuclease activity of hPMC2, indicating the relative importance of the catalytic residues. Western blot analysis of breast cancer cell lines for Quinone Reductase (QR) levels revealed that the intrinsic exonuclease activity of hPMC2 was required for TOT-induced QR upregulation. Chromatin immunoprecipitation (ChIP) assays also indicated that hPMC2 was involved in the formation of strand breaks observed with TOT treatment and is specific for the EpRE-containing region of the QR gene. We also determined that the transcription factor NF-E2-related factor-2 (Nrf2) is involved in the specificity of hPMC2 for the EpRE. In addition, we determined that the catalytic activity of hPMC2 is required for repair of abasic sites that result from estrogen-induced DNA damage. Thus, our study provides a mechanistic basis for transcriptional regulation by hPMC2 and provides novel insights into its role in cancer prevention.

Serum cystatin C levels in renal transplant recipients.

Cystatin C is an emerging parameter for the assessment of renal allograft function. The objective of the study was to compare the efficacy of serum cystatin C (SCys) with the established parameter serum creatinine (SCr) in the assessment of renal function in renal transplant recipients (RTR). The glomerular filtration rate (GFR) of 30 renal transplant patients and 29 control subjects was determined using (99m)Tc Diethylene-triamine-penta-acetate (DTPA) method. SCr was measured using an automated Jaffe's assay and SCys was measured using latex particle enhanced turbidimetric immuno assay (PETIA). The modification of diet in renal disease (MDRD) formula was used to calculate GFR from SCr, while the Le Bricon formula was used to derive GFR based on SCys. Statistical analysis was performed using MedCalc software. SCr and SCys levels were significantly higher, while DTPA clearance was significantly lower in RTR (P < 0.0001) when compared with controls. The correlation coefficient (r value) between calculated GFR based on MDRD method and DTPA clearance was 0.343 (P = 0.06) while the calculated GFR based on Le Bricon formula was 0.694 (P < 0.001). The results have shown that SCys is a better parameter than SCr in assessing renal function in RTR. The inclusion of SCys as an additional parameter would certainly help in detection of even a marginal decline in renal function and also in adjusting the dosage of immunosuppressive drugs.

The possibility of a fully automated procedure for radiosynthesis of fluorine-18-labeled fluoromisonidazole using a simplified single, neutral alumina column purification procedure.

A novel fully automated radiosynthesis procedure for [(18)F]Fluoromisonidazole using a simple alumina cartridge-column for purification instead of conventionally used semi-preparative HPLC was developed. [(18)F]FMISO was prepared via a one-pot, two-step synthesis procedure using a modified nuclear interface synthesis module. Nucleophilic fluorination of the precursor molecule 1-(2'-nitro-1'-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulphonylpropanediol (NITTP) with no-carrier added [(18)F]fluoride followed by hydrolysis of the protecting group with 1M HCl. Purification was carried out using a single neutral alumina cartridge-column instead of semi-preparative HPLC. The maximum overall radiochemical yield obtained was 37.49+/-1.68% with 10mg NITTP (n=3, without any decay correction) and the total synthesis time was 40+/-1 min. The radiochemical purity was greater than 95% and the product was devoid of other chemical impurities including residual aluminum and acetonitrile. The biodistribution study in fibrosarcoma tumor model showed maximum uptake in tumor, 2h post injection. Finally, PET/CT imaging studies in normal healthy rabbit, showed clear uptake in the organs involved in the metabolic process of MISO. No bone uptake was observed excluding the presence of free [(18)F]fluoride. The reported method can be easily adapted in any commercial FDG synthesis module.

Effect of hemodialysis on circulating cystatin c levels in patients with end stage renal disease.

Plasma cystatin C is an emerging parameter to assess kidney function. Its utility in assessing the adequacy of hemodialysis in patients with end-stage-renal disease has however not been established with certainty. This study was therefore carried out to assess the usefulness of serum cystatin C estimation in patients undergoing low flux membrane hemodialysis. Serum creatinine and cystatin C were estimated in 20 patients before and after undergoing hemodialysis. The mean serum creatinine decreased from a pre-dialysis value of 7.72 mg/dL to a post-dialysis value of 2.90 mg/dL. On the contrary, the mean serum cystatin C levels were found to increase from a pre-dialysis value of 5.97 mg/L to a post-dialysis value of 8.25 mg/L. Therefore, serum cystatin C cannot be used to monitor dialysis adequacy. It however, serves as a surrogate marker of the inadequacy of low flux membrane bicarbonate hemodialysis in clearing low molecular weight proteins from the circulation.

UPF201 archaeal specific family members reveal structural similarity to RNA-binding proteins but low likelihood for RNA-binding function.

We have determined X-ray crystal structures of four members of an archaeal specific family of proteins of unknown function (UPF0201; Pfam classification: DUF54) to advance our understanding of the genetic repertoire of archaea. Despite low pairwise amino acid sequence identities (10-40%) and the absence of conserved sequence motifs, the three-dimensional structures of these proteins are remarkably similar to one another. Their common polypeptide chain fold, encompassing a five-stranded antiparallel beta-sheet and five alpha-helices, proved to be quite unexpectedly similar to that of the RRM-type RNA-binding domain of the ribosomal L5 protein, which is responsible for binding the 5S- rRNA. Structure-based sequence alignments enabled construction of a phylogenetic tree relating UPF0201 family members to L5 ribosomal proteins and other structurally similar RNA binding proteins, thereby expanding our understanding of the evolutionary purview of the RRM superfamily. Analyses of the surfaces of these newly determined UPF0201 structures suggest that they probably do not function as RNA binding proteins, and that this domain specific family of proteins has acquired a novel function in archaebacteria, which awaits experimental elucidation.

Wavelength dependant quenching of 2,5-diphenyloxazole fluorescence by nucleotides.

The quenching of 2,5-diphenyloxazole (PPO) fluorescence by nucleotides has been investigated by electronic absorption and steady state fluorescence spectra. Five purine nucleotides AMP, ADP, ATP, GMP and dGMP, one pyrimidine nucleotide UMP and one dinucleotide NAD have been employed in the present study. Electronic absorption studies indicate that there is no ground state complexation between the nucleotides and PPO. The quenching of PPO fluorescence was investigated at two different wavelengths. When excited at 304 nm, the lambda(max) of PPO, the fluorescence spectra of PPO is quenched following Stern-Volmer kinetics. The quenching ability of nucleotides are in the order NAD>AMP>ADP>GMP>dGMP>UMP. The K(SV) and k(q) values obtained indicate that AMP is a better quencher of PPO fluorescence than GMP, which is contrary to commonly observed pattern. The quenching is found to be dynamic in nature. However, when excited at 260 nm, the absorption maximum of the nucleotides, the fluorescence intensity of PPO is reduced with increase in the concentration of the nucleotide. This is attributed to the primary inner filter effect arising due to the absorption of the incident radiation by the nucleotides. Thus the inner filter effect phenomenon can be employed to assay the non-fluorescent molecules by fluorimetry.

Dye induced quenching of firefly luciferase-luciferin bioluminescence.

The quenching of firefly bioluminescence (BL) in presence of xanthene dyes and tetratolylporphyrin was investigated. The BL intensity was quenched with an altered decay pattern in presence of xanthene dyes and tetratolylporphyrin. The electronic absorption spectra indicate that there is no significant interaction occurring between the dyes and the BL components in the ground state. The BL quenching decay rate and fluorescence quenching studies of luciferin by the dyes suggest an energy transfer through an exciplex, involving oxyluciferin, in the excited state and the dyes, in the ground state. The bimolecular quenching rate constant (K(q)) values obtained from fluorescence studies varied between 7.7 x 10(12) and 19.8 x 10(12)M(-1)s(-1). The magnitude of the bimolecular quenching rate constants confirmed the complex formation between dye and excited oxyluciferin. The exciplex subsequently undergoes a non-radiative decay to the ground state via a combination of heavy atom induced and Förster-type energy transfer. The decay rate constants in presence and in absence of dyes vary between 7.47 x 10(-4) and 7.6 x 10(-2)s(-1). In the presence of dyes the effective decay rate constants (k(eff)) increased while the lifetime of light emitting species decreased. The kinetic studies in presence of singlet oxygen scavengers, like beta-carotene and NaN(3), prove that there is no significant quenching of the firefly BL due to the formation of singlet oxygen.