Angiokeratomas are a group of vascular ectasias that involve the papillary dermis and may produce papillomatosis, acanthosis and hyperkeratosis of the epidermis. Angiokeratoma circumscriptum is the least common variant among many types. Angiokeratoma circumscriptum neviforme is a still rarer variety of angiokeratoma, which is classically seen at birth. We report here a case of congenital, linear, unilateral, verrucous plaques on the leg of a young girl, diagnosed as angiokeratoma circumscriptum neviforme (ACN).
A 64-year-old man presented with asymptomatic eruption on his right forearm and the dorsum of the hand present for 2 weeks. There was no history of trauma, prolonged sun exposure, or application of or contact with any substance prior to the development of lesions. He was a known hypertensive and diabetic and was taking treatment for these conditions. The rest of his history was noncontributory. On examination, multiple grouped tiny white papules were found on both normal skin and on the erythematous plaque. These papules were of almost uniform size (2-4 mm) and were notable for absence of umbilication. The erythematous plaque was roughly 15 cm in length and was extending along the ulnar border of forearm and dorsum of hand in a linear pattern (Figure 1). The surface temperature of the plaque appeared similar to the surrounding area, and the surface was studded with multiple tiny white papules. There were no lesions suggestive of chronic actinic damage in the surrounding area. The papules revealed solid whitish material on expression with a needle. The rest of the mucocutaneous examination was noncontributory. Based on clinical presentation, a diagnosis of linear milia en plaque was made.
We theoretically investigated OH-initiated hydrogen abstraction reactions of methyl fluoroacetate (MFA) CH2FC(O)OCH3 at the MPWB1K level of theory in conjunction with the 6-31+G(d,p) basis set. Thermodynamic and kinetic data are computed using the comparatively accurate G2(MP2) method. Two most stable conformers of MFA are identified, and the energy difference between them is found to be only 0.32 kcal mol(-1). Both of them are considered for rate coefficient calculations, and the contribution from each of the conformers is found to be quite significant. We propose an indirect mechanism due to validation of pre- and post-reactive complexes. The rate parameters are determined using canonical transition state theory and energetics at the G2(MP2) level. The temperature dependence of the rate constant can be described by the Arrhenius expressions: k = 8.79 × 10(-13) exp[(-377.27 ± 64)/T] cm(3) molecule(-1) s(-1) over a temperature range of 250-450 K. The ?fH°298 for CH2FC(O)OCH3, CH2FC(O)OC(•)H2, and C(•)HFC(O)OCH3 are also computed using an isodesmic procedure. The OH-driven atmospheric lifetime of MFA was estimated to be 24 days. A mechanistic study to shed light on the atmospheric degradation and the sole fate for the consumption of CH2FC(O)OCH2O(•) radical has also been reported.
Sarcoidosis affects different systems of the body including the skin where it can affect various cutaneous sites. Among these sites, the scalp is a very unusual location for lesions of sarcoidosis. Sarcoidosis of the scalp can very rarely be accompanied by cicatricial alopecia. We report here a rare case of sarcoidosis of scalp with cicatricial alopecia. To the best of our knowledge, this is the first such report from India.
Context: Polymers have been largely explored for the preparation of nanoparticles due to ease of preparation and modification, large gene/drug loading capacity, and biocompatibility. Various methods have been adapted for the preparation and characterization of chitosan nanoparticles. Objective: Focus on the different methods of preparation and characterization of chitosan nanoparticles. Methods: Detailed literature survey has been done for the studies reporting various methods of preparation and characterization of chitosan nanoparticles. Results and conclusion: Published database suggests of several methods which have been developed for the preparation and characterization of chitosan nanoparticles as per the application.
The nucleus accumbens is a critical mediator of depression-related outcomes to social defeat stress. Previous studies demonstrate distinct neuroplasticity adaptations in the two medium spiny neuron (MSN) subtypes, those enriched in dopamine receptor D1 versus dopamine receptor D2, in reward and reinforcement leading to opposing roles for these MSNs in these behaviors. However, the distinct roles of nucleus accumbens MSN subtypes, in depression, remain poorly understood.
Rabeprazole, a member of substituted benzimidazoles, inhibits the final step in gastric acid secretions. This drug claims to cause fastest acid separation (due to higher pKa), and more rapidly converts to the active species to aid gastric mucin synthesis. The most significant pharmacological action of Rabeprazole is dose dependent suppression of gastric acid secretion; without anticholinergic or H2-blocking action. It completely abolishes the hydrochloric acid secretion as it is powerful inhibitor of gastric acid. Rabeprazole is acid labile and hence commonly formulated as an enteric coated tablet. The absorption of rabeprazole occurs rapidly as soon as tablet leaves the stomach.
The present study concerns measurements of radon emissions from soil carried out during March to July 2013 at Chite fault in Aizawl district, Mizoram, India. In this study, continuous radon monitoring in soil was done by using LR-115 type II nuclear track detector (Kodak-Pathe, France make), and the exposed films were replaced weekly. A negative correlation coefficient (-0.47) between radon concentration and barometric pressure was found during the investigation period. The average radon concentration was observed to be 1785.71 Bq m(-3) with a standard deviation of 633.07 Bq m(-3). The maximum and minimum values of radon concentration during this period were found to be 3693.88 and 904.76 Bq m(-3), respectively. An anomalous increase in radon concentration was observed on 112th day (i.e. on 14 June 2013) during the investigation period just 1 d prior to the event of M 3.5, which occurred within 120-km distance from the monitoring site.
Context: The size of nanoparticles plays a pivotal role in determining the gene delivery efficiency. Objective: A focus on the studies done to investigate the effect of nanoparticles size on biological aspects of gene delivery. Methods: A through literature survey has been done regarding studies done to investigate the effect of nanoparticles size on uptake, transfection efficiency and biodistribution has been cited in the present review. Results and conclusion: The gene delivery efficacy may depend on conjugation of several factors such as the chemical structure of polymers, cell type, and nanoparticle size, composition and interaction with cells.
To evaluate difference in the expression of skin color genes (melanocortin 1 receptor (MC1R) and premelanosome (PMEL)) in lymphocytes during winter and summer season and their correlation with tyrosinase enzyme and cortisol, ten Karan-Fries heifers were selected from National Dairy Research Institute (NDRI) cattle farm. Blood samples were collected from the animals during winter (THI?=?60) and summer (THI?=?83) season at weekly intervals. Relative MC1R and PMEL messenger RNA (mRNA) expression of Karan Fries cattle was found to be significantly (P?0.01) higher during winter than summer. Similarly, tyrosinase activity during winter was found to be significantly (P?0.01) higher than summer season. However, plasma cortisol level was significantly (P?0.01) higher during summer than winter. Thus, expression of the skin color genes showed positive correlation with tyrosinase enzyme, but negative correlation with cortisol level. Expression of MC1R and PMEL in lymphocytes and tyrosinase activity of Karan Fries cattle was highly reduced during summer. The present study showed that the ability of Karan Fries cattle to protect themselves from the harmful radiation of sunlight by melanization decreased with increased heat stress on them.
Mango malformation is the most dangerous disease to mango worldwide. There are hints that Fusarium mangiferae might be one of the probable casual agents of disease. Recently, we reported on Fusarium isolates obtained from the mango tarai region of Uttarakhand acquiring morphological features of F. mangiferae. Here, further confirmation of Fusarium isolates were made by PCR amplification using primers specific to the translation elongation factors 1? and ?-tubulin gene of F. mangiferae. Further, SDS-PAGE and RAPD profiles showed genetic variability among isolates of F. mangiferae. This study provides further direct evidence of involvement of different strains of F. mangiferae in malformation diseases of mango in the tarai region of the Uttarakhand state.
In present investigation, bleomycin sulphate loaded nanostructured lipid particles (BLM-NLPs) were constructed to enhance the oral bioavailability by overwhelming the first pass hepatic metabolism. The particles size and nanoencapsulation efficiency of BLM-NLPs were measured to be 17.4±5.4nm and 45.3±3.4%, respectively. Our studies indicated that the drug was molecularly dispersed in the lipid nanocoacervates, with amorphous geometry, without altering the chemical structure, as ascertained by spectral studies. The nanoformulation, BLM-NLPs was analyzed for dissolution testing, cytotoxicity, apoptosis and cellular uptake in human cervical cancer cell line, HeLa cells. BLM-NLPs released the drug with first order kinetic in simulated intestinal fluid (pH?6.8±0.1), characterized by initial burst and followed by slow release. Further, an enhanced cytotoxicity (?5.6 fold lower IC50), improved intracellular concentration (?4.38 fold) and greater degree of apoptosis was induced by BLM-NLPs in HeLa cells, as compared to BLM alone. Moreover, BLM-NLPs also showed dose-dependent internalization, as evinced by cellular uptake study. The in vivo study indicated a significantly (P<0.0001) smaller elimination rate constant (KE), volume of distribution (Vd) and clearance rate (CLTotal) for BLM-NLPs, as compared to BLM solution in post-oral administrations. This clearly depicts the retention and stability of tailored nanoformulation in intestinal absorption pathway. In addition, our nanoformulation, BLM-NLPs documented significantly (P<0.0001)?3.4 fold (66.20±2.57%) higher bioavailability than BLM solution (19.56±0.79%). In conclusion, our in vitro and in vivo results warrant the safety, efficacy and potency of tailored nanoformulation in clinical settings.
Malaria parasite transmission requires the successful development of Plasmodium gametocytes into flagellated microgametes upon mosquito blood ingestion, and the subsequent fertilization of microgametes and macrogametes for the development of motile zygotes, called ookinetes, which invade and transverse the Anopheles vector mosquito midgut at around 18-36?h after blood ingestion. Within the mosquito midgut, the malaria parasite has to withstand the mosquito's innate immune response and the detrimental effect of its commensal bacterial flora. We have assessed the midgut colonization capacity of five gut bacterial isolates from field-derived, and two from laboratory colony, mosquitoes and their effect on Plasmodium development in vivo and in vitro, along with their impact on mosquito survival. Some bacterial isolates activated the mosquito's immune system, affected the mosquito's lifespan, and were capable of blocking Plasmodium development. We have also shown that the ability of these bacteria to inhibit the parasites is likely to involve different mechanisms and factors. A Serratia marcescens isolate was particularly efficient in colonizing the mosquitoes' gut, compromising mosquito survival and inhibiting both Plasmodium sexual- and asexual-stage through secreted factors, thereby rendering it a potential candidate for the development of a malaria transmission intervention strategy.
As world population increases, lactic acid fermentation is expected to become an important role in preserving fresh vegetables, fruits, and other food items for feeding humanity in developing countries. However, several fermented fruits and vegetables products (Sauerkraut, Kimchi, Gundruk, Khalpi, Sinki, etc.) have a long history in human nutrition from ancient ages and are associated with the several social aspects of different communities. Among the food items, fruits and vegetables are easily perishable commodities due to their high water activity and nutritive values. These conditions are more critical in tropical and subtropical countries which favour the growth of spoilage causing microorganisms. Lactic acid fermentation increases shelf life of fruits and vegetables and also enhances several beneficial properties, including nutritive value and flavours, and reduces toxicity. Fermented fruits and vegetables can be used as a potential source of probiotics as they harbour several lactic acid bacteria such as Lactobacillus plantarum, L. pentosus, L. brevis, L. acidophilus, L. fermentum, Leuconostoc fallax, and L. mesenteroides. As a whole, the traditionally fermented fruits and vegetables not only serve as food supplements but also attribute towards health benefits. This review aims to describe some important Asian fermented fruits and vegetables and their significance as a potential source of probiotics.
Detailed theoretical investigation has been performed on the mechanism, kinetics and thermochemistry of the gas phase reactions of CF3CH2OCH3 (HFE-263fb2) with OH radicals using ab-initio and DFT methods. Reaction profiles are modeled including the formation of pre-reactive and post-reactive complexes at entrance and exit channels, respectively. Our calculations reveal that hydrogen abstraction from the CH2 group is thermodynamically and kinetically more facile than that from the CH3 group. Using group-balanced isodesmic reactions, the standard enthalpies of formation for CF3CH2OCH3 and radicals (CF3CHOCH3 and CF3CH2OCH2) are also reported for the first time. The calculated bond dissociation energies for the CH bonds are in good agreement with experimental results. At 298K, the calculated total rate coefficient for CF3CH2OCH3+OH reactions is found to be in good agreement with the experimental results. The atmospheric fate of the alkoxy radicals, CF3CH(O)OCH3 and CF3CH2OCH2O are also investigated for the first time using the same level of theory. Out of three plausible decomposition channels, our results clearly point out that reaction with O2 is not the dominant path leading to the formation of CF3C(O)OCH3 for the decomposition of CF3CH(O)OCH3 radical in the atmosphere. This is in accord with the recent report of Osterstrom et al. [CPL 524 (2012) 32] but found to be in contradiction with experimental finding of Oyaro et al. [JPCA 109 (2005) 337].
A theoretical study on the mechanism and kinetics of the gas phase reactions of CF3CHFCF2OCH2CF3 (HFE-449mec-f) with the OH radicals and Cl atom have been performed using meta-hybrid modern density functional M06-2X using 6-31+G(d,p) basis set. Two conformers have been identified for CF3CHFCF2OCH2CF3 and the most stable one is considered for detailed study. Reaction profiles for OH-initiated hydrogen abstraction are modeled including the formation of pre-reactive and post-reactive complexes at entrance and exit channels. Our calculations reveal that hydrogen abstraction from the CH2 group is thermodynamically and kinetically more facile than that from the CHF group. Using group-balanced isodesmic reactions, the standard enthalpies of formation for HFE-449mecf and radicals generated by hydrogen abstraction, are also reported. The calculated bond dissociation energies for CH bonds are in good agreement with experimental results. The rate constants of the two reactions are determined for the first time in a wide temperature range of 250-450K. The calculated rate constant values are found to be 9.10×10(-15) and 4.77×10(-17)cm(3)molecule(-1)s(-1) for reactions with OH radicals and Cl atom, respectively. At 298K, the total calculated rate coefficient for reactions with OH radical is in good agreement with the experimental results. The atmospheric life time of HFE-449mec-f is estimated to be 0.287 years.
Abstract Context: Kanpur is a major leather processing center in India, where a large number of tanneries are situated. During tanning process, workers are constantly exposed to heat, leather dust produced in buffering operations and a wide range of chemicals. All these factors are known to cause dry eye. Being ophthalmologists of a tertiary health care center in Kanpur, we used to notice over a period of time that a considerable number of patients with dry eye symptoms, attending our out-patient department, were related to leather tanning industries. But, no published data is available on the prevalence of and risk factors for dry eye disorders among tannery worker. Objective: To estimate the prevalence of dry eye problem and its severity among the workers of leather tanneries in the industrial belt of Kanpur and to evaluate various risk factors related to it. Methods: In this cross-sectional case-control study, Ocular Surface Disease Index (OSDI) Questionnaire was presented to randomly selected tannery workers and control group. OSDI score was calculated based on subjects' response, and was evaluated with OSDI chart to assess the magnitude of dry eye symptoms and to grade its severity. Results were analyzed statistically to evaluate the significance level. Results: A total of 800 workers were selected by simple random sampling, out of which 72 workers were excluded from the study. Thus the questionnaire was presented to a total of 728 workers, while control group included 260 individuals. All the workers as well as controls were male with age ranging from 20 to 59 years. The mean age for tannery workers was 34.05?±?8.96 years and that for control group was 32.97?±?10.59 years (p?=?0.14). The tannery workers had mean duration of work at tanneries for 6.99?±?4.86 years. The prevalence of dry eye symptoms among tannery workers was 33.79% (95% CI: 30.35-37.24), while that in control group was 15.77% (95% CI: 11.31-20.23) (p?0.0001). Among symptomatic workers, 47.96% (95% CI: 41.68-54.26) workers had mild, 36.99% (95% CI: 30.91-43.07) workers had moderate and 15.04% (95% CI: 10.54-19.54) workers had severe dry eye symptoms. Severe symptoms were more prevalent among symptomatic workers of age ?40 years in comparison to those <40 years (34.72% versus 6.90%, p?0.0001). With increase in duration of work (1-5, 6-15 and 16-25 years), both prevalence and severity of dry eye symptoms increased significantly (p?=?0.036 and <0.0001, respectively). Conclusion: Dry eye is a significantly prevalent occupational hazard among tannery workers, severity of which increases with the age and the duration of work in tannery. Chemical exposure in hot and dusty working environment of a tannery may have a causative role. Tannery workers should be motivated to use various preventive measures to reduce chemical and dust exposure such as wearing protective glasses, and their ocular health should be monitored periodically for adequate and timely treatment, if required.
: Air pollution has been a matter of great concern globally because of the associated health risks to individuals. The situation is getting worse in developing countries with more urbanization, industrialization and more importantly the rapidly growing population posing a threat to human life in the form of pulmonary, cardiovascular, carcinogenic or asthmatic diseases by accumulating toxic pollutants, harmful gases, metals, hydrocarbons etc.
Zn-silica nanocomposite thin films with varying Zn metal content, deposited by atom beam sputtering technique were subjected to 100 MeV Ag ion irradiation. Rutherford backscattering spectrometry reveals the loss of Zn with irradiation, which is observed to be greater from thin films with lower Zn content. The sputtered species collected on carbon-coated transmission electron microscopy (TEM) grids consist of Zn nanoparticles of sizes comparable to those present in the nanocomposite thin film. The process of size-dependent electronic sputtering of Zn is explained on the basis of an inelastic thermal spike model. The possibility of direct cluster emission is explained by pressure spike built inside the track, initiated by a temperature spike.
Blood transfusions are routinely done in every medical regimen and a worldwide established collection, processing/storage centers provide their services for the same. There have been extreme global demands for both raising the current collections and supply of safe/adequate blood due to increasingly demanding population. With, various risks remain associated with the donor derived blood, and a number of post collection blood screening and processing methods put extreme constraints on supply system especially in the underdeveloped countries. A logistic approach to manufacture erythrocytes ex-vivo by using modern tissue culture techniques have surfaced in the past few years. There are several reports showing the possibilities of RBCs (and even platelets/neutrophils) expansion under tightly regulated conditions. In fact, ex vivo synthesis of the few units of clinical grade RBCs from a single dose of starting material such as umbilical cord blood (CB) has been well established. Similarly, many different sources are also being explored for the same purpose, such as embryonic stem cells, induced pluripotent stem cells. However, the major concerns remain elusive before the manufacture and clinical use of different blood components may be used to successfully replace the present system of donor derived blood transfusion. The most important factor shall include the large scale of RBCs production from each donated unit within a limited time period and cost of their production, both of these issues need to be handled carefully since many of the recipients among developing countries are unable to pay even for the freely available donor derived blood. Anyways, keeping these issues in mind, present article shall be focused on the possibilities of blood production and their use in the near future.
The evolutionarily conserved innate immune system plays critical role for maintaining the health of an organism. However, a number of environmental chemicals including metals are known to exert adverse effects on immune system. The present study assessed the in vivo effect of a major environmental chemical, Cr(VI), on cellular immune response using Drosophila melanogaster and subsequently the protective role of superoxide dismutase (SOD) based on the comparable performance of the tested anti-oxidant enzymes. The immuno-modulatory potential of Cr(VI) was demonstrated by observing a significant reduction in the total hemocyte count along with impaired phagocytic activity in exposed organism. Concurrently, a significant increase in the percentage of Annexin V-FITC positive cells, activation of DEVDase activity, generation of free radical species along with inhibition of anti-oxidant enzyme activities was observed in the hemocytes of exposed organism. In addition, we have shown that ONOO(-) is primarily responsible for Cr(VI) induced adverse effects on Drosophila hemocytes along with O2(-). While generation of O2(-)/ONOO(-) in Cr(VI) exposed Drosophila hemocytes was found to be responsible for the suppression of Drosophila cellular immune response, Cr(VI) induced alteration was significantly reduced by the over-expression of sod in Drosophila hemocytes. Overall, our results suggest that manipulation of one of the anti-oxidant genes, sod, benefits the organism from Cr(VI) induced alteration in cellular immunity. Further, this study demonstrates the applicability of D. melanogaster to examine the possible effects of environmental chemicals on innate immunity which can be extrapolated to higher organisms due to evolutionary conservation of innate immune system between Drosophila and mammals.
Mucosal healing in inflammatory bowel disease (IBD) can be achieved by improvement of intestinal barrier protection. Activation of hypoxia-inducible factor (HIF) has been identified as a critical factor for barrier protection during mucosal insult and is linked with improvement in symptoms of colitis. Although prophylactic efficacy of HIF hydroxylase inhibitors in murine colitis have been established, its therapeutic efficacy in clinically relevant therapeutic settings have not been established. In the present study we aim to establish therapeutic efficacy of TRC160334, a novel HIF hydroxylase inhibitor, in animal models of colitis.
A 24-year-old man presented with multiple mildly itchy flesh-colored papules and plaques on both legs for the past decade. The lesions were preceded by transient vesicles that contained clear fluid. The papules and plaques used to develop on sites where vesicles had healed. Many family members in three generations had similar lesions (Figure 1). On examination, multiple discrete flesh-colored papules and plaques were found on both lower extremities, extending from the feet up to the knees (Figures 2 and 3). A few of the plaques were excoriated. No vesicles or bullae were noted, and the skin in between the lesions appeared normal. The nail of left great toe was discolored and dystrophic. The rest of the mucocutaneous examination was unremarkable. Bullous lichen planus, Neckams disease, lichenoid amyloidosis, and epidermolysis bullosa pruriginosa (EBP) were considered as differential diagnoses. Histopathology from the plaque showed a subepidermal cleft with no inflammatory cells. The epidermis was acanthotic at places, and the dermis appeared normal (Figure 4a and 4b). Based on clinical presentation and histopathology, a diagnosis of EBP was made.
The transcription factor, ?FosB, is robustly and persistently induced in striatum by several chronic stimuli, such as drugs of abuse, antipsychotic drugs, natural rewards, and stress. However, very few studies have examined the degree of ?FosB induction in the two striatal medium spiny neuron (MSN) subtypes. We make use of fluorescent reporter BAC transgenic mice to evaluate induction of ?FosB in dopamine receptor 1 (D1) enriched and dopamine receptor 2 (D2) enriched MSNs in ventral striatum, nucleus accumbens (NAc) shell and core, and in dorsal striatum (dStr) after chronic exposure to several drugs of abuse including cocaine, ethanol, ?(9)-tetrahydrocannabinol, and opiates; the antipsychotic drug, haloperidol; juvenile enrichment; sucrose drinking; calorie restriction; the serotonin selective reuptake inhibitor antidepressant, fluoxetine; and social defeat stress. Our findings demonstrate that chronic exposure to many stimuli induces ?FosB in an MSN-subtype selective pattern across all three striatal regions. To explore the circuit-mediated induction of ?FosB in striatum, we use optogenetics to enhance activity in limbic brain regions that send synaptic inputs to NAc; these regions include the ventral tegmental area and several glutamatergic afferent regions: medial prefrontal cortex, amygdala, and ventral hippocampus. These optogenetic conditions lead to highly distinct patterns of ?FosB induction in MSN subtypes in NAc core and shell. Together, these findings establish selective patterns of ?FosB induction in striatal MSN subtypes in response to chronic stimuli and provide novel insight into the circuit-level mechanisms of ?FosB induction in striatum.
Strains of Pseudomonas aeruginosa (PA) isolated from the airways of cystic fibrosis patients constitutively add palmitate to lipid A, the membrane anchor of lipopolysaccharide. The PhoPQ regulated enzyme PagP is responsible for the transfer of palmitate from outer membrane phospholipids to lipid A. This enzyme had previously been identified in many pathogenic Gram-negative bacteria, but in PA had remained elusive, despite abundant evidence that its lipid A contains palmitate. Using a combined genetic and biochemical approach, we identified PA1343 as the PA gene encoding PagP. Although PA1343 lacks obvious primary structural similarity with known PagP enzymes, the ?-barrel tertiary structure with an interior hydrocarbon ruler appears to be conserved. PA PagP transfers palmitate to the 3 position of lipid A, in contrast to the 2 position seen with the enterobacterial PagP. Palmitoylated PA lipid A alters host innate immune responses, including increased resistance to some antimicrobial peptides and an elevated pro-inflammatory response, consistent with the synthesis of a hexa-acylated structure preferentially recognized by the TLR4/MD2 complex. Palmitoylation commonly confers resistance to cationic antimicrobial peptides, however, increased cytokine production resulting in inflammation is not seen with other palmitoylated lipid A, indicating a unique role for this modification in PA pathogenesis.
This review introduces the Noscapine, which is being used as an antitussive drug for a long time has been recently discovered as a novel tubulin-binding, anti-angiogenic anticancer drug that causes cell cycle arrest and induces apoptosis in cancer cells both in vitro as well as in vivo. Noscapine is a multifunctional molecule i.e. it possesses various functional moieties. We maneuvered various amenable sites and have synthesized analogs, which might prove to be more efficacious and less cytotoxic. Moreover, development of oral controlled release anticancer formulation of noscapine is severely hampered due to short biological half-life (<2-h), poor absorption, low aqueous solubility, and extensive first pass metabolism, thereby requiring large doses for effective treatment.
Telmisartan (TEL) requires superior bioavailability in cancer cell compartments. To meet these challenges, we have synthesized a 2-HP-?-CD-TEL complex with stability constant (Kc) of 2.39×10(-3)mM. The absence in the FTIR spectrum of 2-HP-?-CD-TEL complex of the characteristic peaks of TEL at 1699cm(-1) (carboxylic acid) and 741 and 756cm(-1) (1,2-disubstituted benzene ring vibrations), is indicative of the encapsulation of TEL in the 2-HP-?-CD cavity. DSC and PXRD also confirmed the synthesis and amorphous structure of complex. The interaction of TEL with 2-HP-?-CD was examined by NMR and 2D-ROESY which affirms the encapsulation of TEL in the 2-HP-?-CD cavity in at least two orientations with equal binding energies. The complex also exhibited its superiority in both in vitro release and cytotoxicity experiments on prostate cancer, PC-3 cells as compared to free drug. These data warrant an in depth in vivo to scale-up the technology for the management of prostate cancer.
The growing demand for sustainable animal production is compelling researchers to explore the potential approaches to reduce emissions of greenhouse gases from livestock that are mainly produced by enteric fermentation. Some potential solutions, for instance, the use of chemical inhibitors to reduce methanogenesis, are not feasible in routine use due to their toxicity to ruminants, inhibition of efficient rumen function or other transitory effects. Strategies, such as use of plant secondary metabolites and dietary manipulations have emerged to reduce the methane emission, but these still require extensive research before these can be recommended and deployed in the livestock industry sector. Furthermore, immunization vaccines for methanogens and phages are also under investigation for mitigation of enteric methanogenesis. The increasing knowledge of methanogenic diversity in rumen, DNA sequencing technologies and bioinformatics have paved the way for chemogenomic strategies by targeting methane producers. Chemogenomics will help in finding target enzymes and proteins, which will further assist in the screening of natural as well chemical inhibitors. The construction of a methanogenic gene catalogue through these approaches is an attainable objective. This will lead to understand the microbiome function, its relation with the host and feeds, and therefore, will form the basis of practically viable and eco-friendly methane mitigation approaches, while improving the ruminant productivity.
The essential route to blood parasitaemia in malaria, erythrocyte invasion is facilitated by activation of the G-protein coupled receptor signaling pathway mediated by the ?2-adrenoreceptor as one of the proteins on the surface of red blood cells. The effectiveness of bronchodilators and inhaled corticosteroids in the clinical treatment for asthma patients also depend on polymorphisms in the ?2-adrenoreceptor gene (ADRB2). In a case control study, individuals affected by Plasmodium falciparum malaria, asthma and controls were tested for association of six ADRB2 single nucleotide polymorphisms (SNPs) viz. rs1042711, rs1801704, rs1042713, rs1042714, rs1042717 and rs1042718, by direct DNA sequencing. The rs1801704 locus was significantly associated with malaria when compared against controls. The rs1042713 polymorphism was associated with forced expiratory flow between 25% and 75% of the FVC in asthma patients, pre (p=0.048) and post (p=0.038) treatment measurements. Predicted haplotype of the six SNPs computed from genotype data showed T-T-A-C-G-C conferred significant risk of malaria (p=0.02) whereas T-T-A-C-G-A was associated with risk of asthma (p=0.02). The haplotype T-T-G-C-G-C was protective against both malaria (p=0.02) as well as asthma (p=0.026) and C-C-G-G-G-C was protective uniquely for asthma (p=0.04). A significant outcome was that all variant alleles at the SNP loci were part of the haplotype conferring resistance to malaria disease and asthma, except rs1042713 and rs1042718 which showed very high frequency in asthma. The pairwise linkage disequilibrium (LD) estimates showed a distinct LD block of all SNP loci (D=1 or >0.8) in malaria patients. This characteristic haplotype block was disrupted in the controls due to non-significant pairwise LD of the SNP loci; and a more extensive disruption of the block was noted in asthma patients. The study provides evidence for the proposed role of ?2-adrenoreceptor mediated molecular mechanisms in etiology of malaria, as well as asthma disease and drug response, for further clinical and therapeutic application studies.
Artemisinin form the most important class of antimalarial agents currently available, and is a unique sesquiterpene peroxide occurring as a constituent of Artemisia annua. Artemisinin is effectively used in the treatment of drug-resistant Plasmodium falciparum and because of its rapid clearance of cerebral malaria, many clinically useful semisynthetic drugs for severe and complicated malaria have been developed. However, one of the major disadvantages of using artemisinins is their poor solubility either in oil or water and therefore, in order to overcome this difficulty many derivatives of artemisinin were prepared. A comparative study on the chemical reactivity of artemisinin and some of its derivatives is performed using density functional theory (DFT) calculations. DFT based global and local reactivity descriptors, such as hardness, chemical potential, electrophilicity index, Fukui function, and local philicity calculated at the optimized geometries are used to investigate the usefulness of these descriptors for understanding the reactive nature and reactive sites of the molecules. Multiple regression analysis is applied to build up a quantitative structure-activity relationship (QSAR) model based on the DFT based descriptors against the chloroquine-resistant, mefloquine-sensitive Plasmodium falciparum W-2 clone.
About 10% of the drugs in the preclinical stage are poorly soluble, 40% of the drugs in the pipeline have poor solubility, and even 60% of drugs coming directly from synthesis have aqueous solubility below 0.1 mg/ml. Out of the research around, 40% of lipophilic drug candidates fail to reach the market despite having potential pharmacodynamic activities. Microtubule-modulating chemotherapeutics is an important class of cancer chemotherapy. Most chemotherapeutics that belong to this category are plant-derived active constituents, such as vincristine, vinblastine, colchicine, docetaxel, paclitaxel, and noscapinoids. The pKa of a drug considerably affects its solubility in physiological fluids and consequently bioavailability. It usually ranges from 5 to 12 for microtubule-modulating drugs. Hence, the solubility of these drugs in physiological fluids is considerably affected by a change in pH. However, because of unpredictable parameters involved in poor solubility and the low oral bioavailability of these chemotherapeutics during the early phases of drug development, they often have an unusual pharmacokinetic profile. This makes the development process of novel chemotherapeutics slow, inefficient, patient-unfriendly, and very costly, emphasizing a need for more rational approaches on the basis of preclinical concepts. Nanosolvation is a process of increasing the polarity of a hydrophobic molecule either by solvation or cavitization in a hydrophilic macrocycle. The present review therefore focuses on the techniques applied in nanosolvation of microtubule-modulating chemotherapeutics to enhance solubility and bioavailability. The methodologies described will be highly beneficial for anticancer researchers to follow a trend of rational drug development.
A Theoretical study on the mechanism of the reactions of CF2ClC(O)OCH3 with the OH radical and Cl atom is presented. Geometry optimization and frequency calculations have been performed at the MPWB1K/6-31+G(d,p) level of theory and energetic information is further refined by calculating the energy of the species using G2(MP2) theory. Transition states are searched on the potential energy surface involved during the reaction channels and each of the transition states are characterized by presence of only one imaginary frequency. The existence of transition states on the corresponding potential energy surface is ascertained by performing intrinsic reaction coordinate (IRC) calculation. Theoretically calculated rate constants at 298 K and atmospheric pressure using the canonical transition state theory (CTST) are found to be in good agreement with the experimentally measured ones. Using group-balanced isodesmic reactions as working chemical reactions, the standard enthalpies of formation for CF2ClC(O)OCH3, CF2ClC(O)OCH2 and CF3C(O)OCH3 are also reported for the first time.
Malformation is arguably the most crucial disease of mango (Mangifera indica L.). The etiology of the disease has not yet been successfully resolved. Here, we quantified the endogenous ethylene content in malformed and healthy vegetative and floral tissues of mango cultivars viz., Amrapali, Bombay green, Chausa, Dushehri and Mallika. Levels of ethylene were higher in malformed vegetative and floral tissues as compared with that of healthy tissues at both prior to full bloom and full bloom stages. The study also revealed that isolates of Fusarium dissected from mango exhibited most morphological similarities to the accepted standard features of Fusarium mangiferae. The growth dynamic of F. mangiferae were evaluated with varying temperatures ranging from 5 to 40 °C. Temperatures of 25 °C, 30 °C and 35 °C were better suited for growth of F. mangiferae than temperatures of 20 °C or 40 °C. Conidium germination of F. mangiferae was maximum at 30 °C and minimum at <15 °C. World-wide occurrence of mango malformation showed its most severity at 10-15 °C temperature range. Stress ethylene level is higher in diseased tissue at the same temperature range where growth of Fusaria is found to be completely restricted. The present study provides direct evidence that low temperature induced stress ethylene is potentially responsible for the disease while on the other hand Fusarium role in the disease either through toxic principle or malformation inducing principle is not conclusive at <15 °C and is rather out of question.
We have evaluated the effect of an integrated (nano-bio) technique involving the use of stabilized Pd/Fe(0) bimetallic nanoparticles (CMC-Pd/nFe(0)) and a Sphingomonas sp. strain NM05, on the degradation of ?-HCH in soil. Factors affecting degradation such as pH, incubation temperature and ?-HCH initial concentration were also studied. The results revealed that ?-HCH degradation efficiency is ~ 1.7-2.1 times greater in integrated system as compared to system containing either NM05 or CMC-Pd/nFe(0) alone. The integration showed synergistic effect on ?-HCH degradation. Further, cell growth studies indicated that NM05 gets well acclimatized to nanoparticles, showing potential growth in the presence of CMC-Pd/nFe(0) with respect to control system. This study signifies the potential efficacy of integrated technique to become an effective alternative remedial tool for ?-HCH contaminated soil. Further research in this direction could lead to the development of effective remediation strategies for other isomers of HCH and other chlorinated pesticides as well.
Type 2 diabetes is the most common form of diabetes, accounting for over 90% of cases. Current treatment approaches for type 2 diabetes include diet, exercise, and a variety of pharmacologic agents, including insulin, biguanides, sulfonylureas, and thiazolidinediones.
Theoretical investigations are carried out on reaction mechanism of the reactions of CF3CH2NH2 (TFEA) with the OH radical by means of ab initio and DFT methods. The electronic structure information on the potential energy surface for each reaction is obtained at MPWB1K/6-31+G(d,p) level and energetic information is further refined by calculating the energy of the species with a Gaussian-2 method, G2(MP2). The existence of transition states on the corresponding potential energy surface is ascertained by performing intrinsic reaction coordinate (IRC) calculation. Our calculation indicates that the H abstraction from -NH2 group is the dominant reaction channel because of lower energy barrier. The rate constants of the reaction calculated using canonical transition state theory (CTST) utilizing the ab initio data. The agreement between the theoretical and experimental rate constants is good at the measured temperature. From the comparison with CH3CH2NH2, it is shown that the fluorine substution decreases the reactivity of the C-H bond.
Predicting functions of proteins and alternatively spliced isoforms encoded in a genome is one of the important applications of bioinformatics in the post-genome era. Due to the practical limitation of experimental characterization of all proteins encoded in a genome using biochemical studies, bioinformatics methods provide powerful tools for function annotation and prediction. These methods also help minimize the growing sequence-to-function gap. Phylogenetic profiling is a bioinformatics approach to identify the influence of a trait across species and can be employed to infer the evolutionary history of proteins encoded in genomes. Here we propose an improved phylogenetic profile-based method which considers the co-evolution of the reference genome to derive the basic similarity measure, the background phylogeny of target genomes for profile generation and assigning weights to target genomes. The ordering of genomes and the runs of consecutive matches between the proteins were used to define phylogenetic relationships in the approach. We used Escherichia coli K12 genome as the reference genome and its 4195 proteins were used in the current analysis. We compared our approach with two existing methods and our initial results show that the predictions have outperformed two of the existing approaches. In addition, we have validated our method using a targeted protein-protein interaction network derived from protein-protein interaction database STRING. Our preliminary results indicates that improvement in function prediction can be attained by using coevolution-based similarity measures and the runs on to the same scale instead of computing them in different scales. Our method can be applied at the whole-genome level for annotating hypothetical proteins from prokaryotic genomes.
Exposure to psychostimulants results in structural and synaptic plasticity in striatal medium spiny neurons (MSNs). These cellular adaptations arise from alterations in genes that are highly implicated in the rearrangement of the actin-cytoskeleton, such as T-lymphoma invasion and metastasis 1 (Tiam1). Previous studies have demonstrated a crucial role for dopamine receptor 1 (D1)-containing striatal MSNs in mediating psychostimulant induced plasticity changes. These D1-MSNs in the nucleus accumbens (NAc) positively regulate drug seeking, reward, and locomotor behavioral effects as well as the morphological adaptations of psychostimulant drugs. Here, we demonstrate that rats that actively self-administer cocaine display reduced levels of Tiam1 in the NAc. To further examine the cell type-specific contribution to these changes in Tiam1 we used optogenetics to selectively manipulate NAc D1-MSNs or dopamine receptor 2 (D2) expressing MSNs. We find that repeated channelrhodopsin-2 activation of D1-MSNs but not D2-MSNs caused a down-regulation of Tiam1 levels similar to the effects of cocaine. Further, activation of D2-MSNs, which caused a late blunted cocaine-mediated locomotor behavioral response, did not alter Tiam1 levels. We then examined the contribution of D1-MSNs to the cocaine-mediated decrease of Tiam1. Using the light activated chloride pump, eNpHR3.0 (enhanced Natronomonas pharaonis halorhodopsin 3.0), we selectively inhibited D1-MSNs during cocaine exposure, which resulted in a behavioral blockade of cocaine-induced locomotor sensitization. Moreover, inhibiting these NAc D1-MSNs during cocaine exposure reversed the down-regulation of Tiam1 gene expression and protein levels. These data demonstrate that altering activity in specific neural circuits with optogenetics can impact the underlying molecular substrates of psychostimulant-mediated behavior and function.
A method is described for construction of an amperometric polyphenol biosensor employing nitrocellulose membrane-bound laccase purified from cell-free extract of Ganoderma lucidum onto a Pt electrode. The biosensor showed optimum response within 10s, at 0.4 V in 0.1M acetate buffer, pH 6.0, and 35°C. Detection limit of the biosensor was 3.0 × 10(-8)M. Analytical recovery of added guaiacol was 97.00%. Within batch and between batch coefficients of variation were <0.97% and <1.26%, respectively. The sensor measured total phenolic content in fruit juices and alcoholic beverages. The enzyme electrode was used 100 times over 4 months, when stored at 4°C.
Dysraphisms involving cervical region are very rare and there are very few series describing their follow-up in literature. Here, we report a 6-year-old boy who underwent postnatal "cosmetic" repair of posterior cervical cystic lesion and presented to us with a large recurrence with syringohydromyelia and tethering. Tethered cord should be suspected in the presence of meningocele and intact neurology. Treatment protocols of such complicated cervical spinal dysraphisms should include intradural exploration and detethering, with an aim to prevent neurological deterioration in future.
The design and development of nucleic acids based therapeutics for the treatment of diseases arising from genetic abnormalities has made significant progress over the past few years. Advances in synthetic oligonucleotide chemistry resulted in synthesis of nucleic acids that are relatively stable in in vivo environments. However, cellular targeting and intracellular delivery of nucleic acids still remains a challenge. Further, development of nucleic acids based therapeutics depends on the progress of safe and effective carriers for systemic administration. Cationic vectors with diminished cytotoxicity and enhanced efficacy are rapidly emerging as systems of choice. These vectors protect nucleic acids from enzymatic degradation by forming condensed complexes along with targeted tissue and cellular delivery. During the past few years, myriad of reports have appeared reporting delivery of nucleic acids mediated by nanocarriers. This review provides an overview of various nanocarriers employed for in vitro and in vivo delivery of therapeutically relevant nucleic acids e.g., DNA, siRNA, LNA, PNA etc.
A patent ductus arteriosus (PDA) is often present in patients undergoing correction of congenital heart disease. It is well appreciated that during cardiopulmonary bypass (CPB), a PDA steals arterial inflow into pulmonary circulation, and may lead to systemic hypoperfusion, excessive pulmonary blood flow (PBF) and distention of the left heart. Therefore, PDA is preferably ligated before initiation of CPB. We describe acute decreases of arterial blood pressure and entropy score with the initiation of CPB and immediate increase in entropy score following the PDA ligation in a child undergoing intracardiac repair of ventricular septal defect and right ventricular infundibular stenosis. The observation strongly indicates that a PDA steals arterial inflow into pulmonary circulation and if the PDA is dissected and ligated on CPB or its ligation on CPB is delayed the cerebral perfusion is potentially compromised.
Hip reconstruction with subtrochanteric valgus extension pelvic support osteotomy and distal femoral osteotomy for lengthening and varus correction is one of the options available for salvage of chronic unstable hips and is also known as Ilizarov hip reconstruction (IHR). This study evaluated the outcomes and complications associated with IHR in skeletally mature young patients.
siRNA are a rapidly emerging class of new therapeutic molecules for the treatment of inherited and acquired diseases. However, poor cellular uptake and instability in physiological conditions limits its therapeutic potential, hence a need to develop a delivery system that can protect and efficiently transport siRNA to the target cells has arisen. Nanoparticles have been proposed as suitable delivery vectors with reduced cytotoxicity and enhanced efficacy. These delivery vectors form condensed complexes with siRNA which, in turn, provides protection to siRNA against enzymatic degradation and further leads to tissue and cellular targeting. Nanoparticles derived from polymers, such as chitosan and polyethylenimine have found numerous applications owing to ease of manipulation, high stability, low cost and high gene carrying capability. This article focuses on various aspects of nanomedicine based siRNA delivery with emphasis on targeted delivery to tumors.
Pericardial tamponade limits diastolic filling of the heart; therefore, a high venous pressure is required to fill the ventricle. In presence of cardiac tamponade, therapeutic agents and manoeuvres that results in venodilation or vasodilation can severely compromise diastolic filling of the heart and might result in rapid cardiac decompensation. Equalization of central venous pressure and pulmonary artery diastolic pressure or equalization of pressures in all four chambers during diastole confirms cardiac tamponade. Transthoracic echocardiography can detect the site of tamponade and assist in pericardiocentesis. We describe acute pericardial tamponade in a young man who underwent left posterolateral thoracotomy for left upper lobectomy. Intraoperatively, mobilization of the left upper lobe was frequently associated with hypotension. Postoperatively, the patient suffered two more episodes of hypotension. The episodes of hypotension were attributed to surgical manipulation and epidural blockade. Hemodynamics normalized after discontinuing epidural infusion, volume resuscitation and lobectomy. On third postoperative day, the patient developed cardiovascular collapse; arterial blood pressure and central venous pressure were 70/50 and 12 mmHg. Investigations showed haziness of left lung, and severe respiratory acidosis. On opening of the left thoracotomy wound, pericardial tamponade was diagnosed. A pericardial window was created and tamponade was released with that the hemodynamics normalized. Episodes of unexplained hypotension after left upper lobectomy suggest a cardiac etiology and acute pericardial tamponade is a possibility which should be released immediately otherwise it can result in fatal outcome.
Although Yersinia enterocolitica is usually transmitted through contaminated food and untreated water, occasional transmission such as human-to-human, animal-to-human and blood transfusion associated transmission have also identified in human disease. Of the six Y. enterocolitica biotypes, the virulence of the pathogenic biotypes, namely, 1B and 2-5 is attributed to the presence of a highly conserved 70-kb virulence plasmid, termed pYV/pCD and certain chromosomal genes. Some biotype 1A strains, despite lacking virulence plasmid (pYV) and traditional chromosomal virulence genes, are isolated frequently from humans with gastrointestinal diseases similar to that produced by isolates belonging known pathogenic biotypes. Y. enterocolitica pathogenic biotypes have evolved two major properties: the ability to penetrate the intestinal wall, which is thought to be controlled by plasmid genes, and the production of heat-stable enterotoxin, which is controlled by chromosomal genes.
Noscapine, the tubulin-binding anticancer agent, when administered orally, requires high ED(50) (300-600 mg/kg), whereas intravenous administration (10 mg/kg) results in rapid elimination of the drug with a half-life of 0.39 h. Hence, the development of long-circulating injectable nanoparticles can be an interesting option for designing a viable formulation of noscapine for anticancer activity. Noscapine-enveloped gelatin nanoparticles and poly(ethylene glycol)-grafted gelatin nanoparticles were constructed and characterized. Data indicate that smooth and spherical shaped nanoparticles of 127 ± 15 nm were engineered with maximum entrapment efficiency of 65.32 ± 3.81%. Circular dichroism confirms that nanocoacervates retained the ?-helical content of gelatin in ethanol whereas acetone favored the formation of a random coil. Moreover, the Fourier transform infrared and powder X-ray diffraction pattern prevents any significant change in the noscapine-loaded gelatin nanoparticles in comparison with individual components. In-vitro release kinetic data suggest a first-order release of noscapine (85.1%) from gelatin nanoparticles with a release rate constant of 7.611×10(-3). It is to be noted that there is a 1.43-fold increase in the area under the curve up to the last sampling point for the noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles over the noscapine-loaded gelatin nanoparticles and a 13.09-fold increase over noscapine. Cytotoxicity analysis of the MCF-7 cell line indicated that the IC(50) value of the noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles was equivalent to 20.8 ?mol/l, which was significantly (P<0.05) lower than the IC(50) value of the noscapine-loaded gelatin nanoparticles (26.3 ?mol/l) and noscapine (40.5 ?mol/l).Noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles can be developed as a promising therapeutic agent for the management of breast cancer.
Cisplatin-loaded protransfersome system was prepared and characterized for in vitro drug permeation, drug deposition and antitumor effect. A histopathological study and a genotoxicity study were also done. The skin permeation data of cisplatin from protransfersome gel formulation revealed 494.33 ± 11.87 ?g cm-2, which was significantly higher than that from the control plain drug solution in 0.9 % NaCl (p < 0.001). Untreated group of animals showed invasive moderately differentiated keratinizing squamous cell carcinoma (malignant stage). However, with cisplatin loaded protransfersome gel system simple epithelial hyperplasia (pre-cancerous stage) with no cancerous growth was observed. Also, a significant induction in micronucleus formation was found in the group that was treated with injectable intraperitoneal cisplatin preparation in 0.9 % saline as compared to the group treated with topical protransfersome gel formulation. The findings of this research work appear to support improved, site-specific and localized drug action in the skin, thus providing a better option for dealing with skin related problems like squamous cell carcinoma.
Noscapine and its derivatives are important microtubule-interfering agents shown to have potent anti-tumor activity. The binding free energies (?G (bind)) of noscapinoids computed using linear interaction energy (LIE) method with a surface generalized Born (SGB) continuum solvation model were in agreement with the experimental ?G (bind) with average root mean square error of 0.082 kcal/mol. This LIE-SGB model guided us in designing a novel derivative of noscapine, amino-noscapine [(S)-3-((R)-9-amino-4-methoxy-6-methyl-5,6,7,8-tetrahydro [1, 3] dioxolo[4,5-g]isoquinolin-5-yl)-6,7-dimethoxy isobenzo-furan-1(3H)-one] that has higher tubulin binding activity (predicted ?G (bind) = -6.438 kcal/mol and experimental ?G (bind) = -6.628 kcal/mol) than noscapine, but does not significantly change the total extent of the tubulin subunit/polymer ratio. The modes of interaction of amino-noscapine with the binding pocket of tubulin involved three hydrogen bonds and are distinct compared to noscapine which involved only one hydrogen bond. Also the patterns of non-bonded interactions are albeit different between both the lignads. The blind docking approach (docking of ligand with different binding sites of a protein and their evaluations) as well as the reasonable accuracy of calculating ?G (bind) using LIE-SGB model constitutes the first evidence that this class of compounds binds to tubulin at a site overlapping with colchicine-binding site or close to it. Our results revealed that amino-noscapine has better anti-tumor activity than noscapine.
Malaria is one of the most lethal parasitic infections in the world. The lethality of the parasite depends on the rate of multiplication of the parasite within host erythrocytes. Different strains of the malaria parasite often respond in a different way to the same strain of mice or vice versa. In the present study, we investigated the course of infection of the arteether-sensitive and arteether-resistant Plasmodium vinckei parasites in Swiss albino AKR (inbred) and AJ (outbred) mice. The higher parasite burden and mortality were observed in the sensitive parasite-infected mice, whereas the infection with the resistant parasite was non-lethal. Resistant parasite-infected mice developed a moderate level of parasitemia that decreased gradually throughout the infection. The microscopic examination suggests that the resistant parasite invades reticulocytes more efficiently than normocytes, regardless of the mouse strain examined. Since the reticulocytes are rare in blood circulation, it limits the increase in parasite proliferations, while arteether-sensitive parasites can invade both mature normocytes and reticulocytes, resulting in the mortality of the mice. However, treatment with phenylhydrazine in Swiss mice results in reticulocytosis, which transforms the non-lethal resistant parasites to produce lethal infections. Our findings demonstrate that the characteristic response during infections with the arteether-resistant strain is dependent on the availability of reticulocytes in peripheral blood circulation. We can use this model for identifying the interaction between host and artemisinin derivative-resistant parasites.
A simple, rapid, and solvent-free method for quantitative determination of benzene, toluene, and Xylene in exposed Drosophila larvae was developed using headspace solid-phase microextraction (HS-SPME) coupled to GC/MS. Larvae fed on standard Drosophila food mixed with benzene, toluene, and Xylene for 48 h were homogenized in Milli-Q water. Extraction of benzene, toluene, and Xylene was performed at 65 degrees C for 30 min on the SPME fiber (silica-fused). Subsequently, the fiber was desorbed in the GC injection port, followed by GC/MS analysis in the selected-ion monitoring mode. An external calibration curve was used for the quantification of benzene, toluene, and Xylene in the exposed organism. Recoveries were in the range of 78-82% (intraday) and 76-81% (interday) in larvae, and 91-96% (intraday) and 87-92% (interday) in the diet. LOD with an S/N of 3:1 and LOQ with an S/N of 10:1 were in the range of 0.01-0.023 and 0.034-0.077 microg/L, respectively. Percent RSD values for benzene, toluene, and Xylene were in the range of 0.50-0.81 (intraday) and 0.89-1.23 (interday) for retention time, and 2.16--3.85 (intraday) and 2.99-4.95 (interday) for peak concentration, showing good repeatability. This method was sensitive enough to quantitate benzene, toluene, and Xylene in small exposed organisms like Drosophila larvae. The SPME/GC/MS method developed may have wider applications in various in vivo toxicological studies.
The control of malaria has been complicated by the increasing resistance of malarial parasites to multiple drugs. However, artemisinin-based drugs offer hope in the fight against drug-resistant parasites. The mode of action of these drugs remains unclear, but evidence suggests a role for free radicals in their mechanism of action. In this study, we examined the relationship between the intracellular levels of glutathione (GSH) and antioxidant enzymes and resistance to the artemisinin-based drug arteether in experimentally selected arteether-resistant Plasmodium vinckei. GSH plays a critical role in the detoxification and protection of cells against oxidative stress. Our comparative studies showed a significant (2.9-fold) increase in the GSH level in arteether-resistant parasites as compared to arteether-sensitive parasites. Simultaneously, significantly increased activities of glutathione reductase, glutathione-S transferase and glucose-6-phosphate dehydrogenase and decreased activity of superoxide dismutase were recorded in resistant parasites; the activity of glutathione peroxidase was comparable in arteether-sensitive and -resistant parasites. Artemisinin derivatives act by generating free radicals and our results indicate that glutathiones antioxidant effects may counteract that drug effect and thereby contribute to the parasites resistance to arteether and other artemisinin-based antimalarials.
We report a case of non missile penetrating spinal injury (NMPSI) caused due to an impaled knife in the lumbar region. The patient was neurologically preserved and presented with the knife blade retained in his back. The wound with the knife in situ was explored, the knife removed and a dural laceration was repaired. The wound healed without evidence for cerebrospinal fluid leakage or infection.
In the present work, we report a novel method for the synthesis of palladium and lead nanoparticles by the reduction method in tetrazolium ring based ionic liquid. Palladium and lead nanoparticles so-prepared were well characterized by powder X-ray diffraction measurements (pXRD), transmission electron microscopy (TEM) and quasi elastic light scattering (QELS) techniques. Powder X-ray diffraction (pXRD) analysis revealed all relevant Braggs reflection for crystal structure of palladium and lead. Powder X-ray diffraction plots also revealed no oxidized material of palladium and lead nanoparticles. TEM showed nearly uniform distribution of the particles in methanol and confirmed by QELS. Typical applications of palladium nanoparticles include in vitro use and sensor design applications. Palladium nanoparticles is also ideal for spin coating, self-assembly and monolayer formation. Palladium nanoparticles can also be considered as potential new catalysts.
Children with Waardenburg syndrome (WS) exhibiting normal inner ear anatomy, like those included in our cohort, derive significant benefit from cochlear implantation and results are comparable to those reported for the general population of implanted children.
In the present study, we report the synthesis of ZnO nanostructures using the Vapor-Liquid-Solid growth with different metal catalyst by electron beam evaporation method. As grown samples were characterized by means of Field emission scanning electron microscopy (FESEM), Raman spectroscopy and photoluminescence spectroscopy. FESEM characterization showed the formation of different type of nanostructure depending on the metal catalyst. Array of well aligned nanorods were formed when Au and Fe were used as a catalyst. However, Sn catalyst induced the formation of nanoflakes. The presence of peak at 434 cm(-1) in Raman spectroscopy revealed the wurtzite nature of formed ZnO nanostructures. Nanoflakes showed a more strong UV emission in comparision to that of nanorods as revealed by Photoluminescence spectra.
A laboratory study was conducted to investigate the ability of activated CO(2)-neutralized red mud (ANRM) for the removal of arsenate from the aqueous solutions. The batch adsorption experiments were conducted with respect to adsorbent dose, equilibrium pH, contact time, initial arsenate concentration, kinetics, Langmuir isotherms. The mechanisms involved in adsorption of arsenate ions on ANRM were characterized by using XRD, FT-IR, UV-vis, SEM/EDX, and chemical methods. The percentage removal was found to increase gradually with decrease of pH and maximum removal was achieved at pH approximately 4. Adsorption kinetic studies revealed that the adsorption process followed pseudo-second-order kinetics and equilibrates within 24 h. FT-IR spectra of ANRM before and after adsorption reveals the binding of arsenate to the adsorbent. The adsorption data were fitted to linearly transformed Langmuir isotherm with R(2) (correlation coefficient)>0.99. Arsenate adsorbed ANRM can be regenerated using NaOH solution at pH 12.0.
The ultimate success of micropropagation on a commercial scale depends on the ability to transfer plants out of culture on a large scale, at low cost and with high survival rates. During field transfer the in vitro grown plantlets are unable to compete with soil microbes and to cope with the environmental conditions. The in vitro culture conditions result in the plantlets with altered morphology, anatomy and physiology. In order to increase growth and reduce mortality in plantlets at the acclimatisation stage, efforts are focused on the control of both physical and chemical environment and biohardening of micropropagated plantlets. This review describes the abiotic and biotic stresses and current developing methods for the acclimatization of microshoots.
Talc particles, the basic ingredient in different kinds of talc-based cosmetic and pharmaceutical products, pose a health risk to pulmonary and ovarian systems due to domestic and occupational exposures. Two types of talc nanoparticles depending on the source of geographical origin - indigenous- and commercial talc nanoparticles were assessed for their potential in vitro toxicity on A(549) cells; along with indigenous conventionally used microtalc particles. Cell viability, determined through live/dead staining and 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, decreased as a function of concentration, origin and size of particles. Both varieties of talc nanoparticles differentially induced lipid peroxidation (LPO), which was correlated with the pattern of lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) generation, and glutathione (GSH) depletion. Relatively higher cytotoxicity of indigenous nanotalc could be attributed to its higher content of iron as compared to commercial nanotalc. The known scavenger of ROS, l-ascorbic acid significantly inhibited LPO induction due to talc particles. Data suggest that nanotalc toxicity on A(549) cells was mediated through oxidative stress, wherein role of iron-mediated LPO was much pronounced in differential cytotoxicity.
A laboratory study was conducted to investigate the ability of neutralization of red mud (RM) using carbon dioxide gas sequestration cycle at ambient conditions. The neutralized red mud (NRM) was characterized by XRD, SEM, EDX, FT-IR and auto titration method. X-ray diffraction pattern of NRM was revealed that the intensity of gibbsite was increased prominently and formed ilmenite due to dissolution of minerals. EDX analysis was showed that the %(w/w) of Na, C, O, Si were higher in the carbonated filtrate as compared to the RM and NRM. The permanently sequestered CO(2)%(w/w) per 10 g of red mud were approximately 26.33, approximately 58.01, approximately 55.37, and approximately 54.42 in NRM and first, second, third cycles of carbonated filtrate, respectively. The pH of red mud was decreased from approximately 11.8 to approximately 8.45 and alkalinity was decreased from approximately 10,789 to approximately 178 mg/L. The acid neutralizing capacity of NRM was approximately 0.23 mol H(+)/kg of red mud. The specific advantages of these cyclic processes are that, large amount of CO(2) can be captured as compared to single step.
We have earlier reported that an endoplasmic reticulum luminal protein calreticulin (CR) mediated the acetylation of certain receptor proteins such as glutathione S-transferase (GST) by polyphenolic acetates, leading to irreversible inhibition. This function of calreticulin was termed calreticulin transacetylase. In this communication, we have demonstrated for the first time the ability of the purified recombinant calreticulin of a parasitic nematode Haemonchus contortus to transfer propionyl group from 7,8-Dipropoxy-4-methylcoumarin (DPMC) to recombinant Schistosoma japonicum glutathione S-transferase (rGST). Calreticulin transacetylase exhibited hyperbolic kinetics and yielded K(m) (140 microM) and V(max) (105 units) when the concentration of DPMC was varied keeping the concentration of rGST constant. rGST thus propionylated was found to positively interact with anti-acetyl lysine antibody. Also, the nanoscale LC-MS/MS analysis identified the propionylation sites on three lysine residues: Lys-11, -180 and -181 of rGST. These results highlight the transacylase function of calreticulin (CRTAase).
Information about the health risks or the subtle adverse health effects that might be associated with low-level lead exposure on micronutrient metabolism are scarce in the literature. The present work investigated the subtle adverse health effects of exposure to progressively low levels of lead on the metabolism of two micronutrients, copper and zinc in different tissues of the rat. Rats were exposed to 200, 300 and 400 ppm lead in their drinking water for 12 weeks. Lead, copper and zinc concentrations were determined in blood, liver, kidney, heart, spleen and brain of the animals. While the imbalance in zinc metabolism was characterized by a deposition of zinc in the kidney and to a lesser extent in the heart of the animals, imbalance in copper metabolism was characterized by a depletion of blood and splenic copper concentrations as well as renal and cardiac accumulation of copper. Hepatic and brain copper and zinc contents, together with blood zinc were not affected by the 12-week lead exposure. A linear relationship was observed between lead dose and lead accumulation in the spleen, whereas a non-linear relationship was observed between lead dose and lead accumulation in blood, liver, kidney and heart. Our findings indicate that exposure to progressively low-level lead concentrations results in imbalance in copper and zinc in the organism and this might be a factor in propensity toward behavioral disorders observed in lead exposure.
Diabetes mellitus is a chronic metabolic disorder affecting about 6% of population worldwide with its complications and is rapidly reaching epidemic scale. Cinnamomum zeylanicum is widely used in alternative system of medicine for treatment of diabetes. In the present study, we have performed bioassay guided fractionation of chloroform extract of C. zeylaniucm and identified cinnamaldehyde (CND) as an active principle against diabetes. In continuation to it, a detailed study was undertaken to elucidate its mode of antidiabetic action in STZ induced diabetic rats. Oral administration of CND (20 mg/kg bw) to diabetic rats for 2 months showed significant improvement (p<0.001) in muscle and hepatic glycogen content. In vitro incubation of pancreatic islets with CND enhanced the insulin release compared to glibenclamide. The insulinotropic effect of CND was found to increase the glucose uptake through glucose transporter (GLUT4) translocation in peripheral tissues. The treatment also showed a significant improvement in altered enzyme activities of pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK) and their mRNA expression levels. Furthermore, the median lethal dose (LD(50)) of CND could not be obtained even at 20 times (0.4 g/kg bw) of its effective dose. With the high margin of safety of CND, it can be developed as a potential therapeutic candidate for the treatment of diabetes.
Epileptic seizures are accompanied by changes in autonomic function that in turn influence the cardiovascular system (hypertension and bradyarrhythmia). We have studied possible cardioprotective activity (during the ictal state in conscious animals) of valproic acid, nifedipine, and verapamil, alone and in combination, during pentylenetetrazole (PTZ)-induced seizures. Telemetry system was used for recording EEG, blood pressure, and heart rate in conscious, freely moving rats during seizures. We observed that PTZ-induced seizures were accompanied by hypertension and bradyarrhythmia. Pretreatment with valproic acid did not block seizure-induced hypertension and bradyarrhythmia. Nifedipine alone and in combination with valproic acid blocked seizure-induced hypertension and bradyarrhythmia significantly. We also observed that pretreatment with verapamil alone and in combination with valproic acid did not block seizure-induced hypertension and bradyarrhythmia significantly. Our results suggest that pretreatment with nifedipine alone or in combination with valproic acid provides protection against seizure-induced hypertension and bradyarrhythmia.
Zn0.9Cd0.1S nanoparticles doped with 0.005-0.24 M cobalt have been prepared by co-precipitation technique in ice bath at 280 K. For the cobalt concentration >0.18 M, XRD pattern shows unidentified phases along with Zn0.9Cd0.1S sphalerite phase. For low cobalt concentration (?0.05 M) particle size, dXRDis ~3.5 nm, while for high cobalt concentration (>0.05 M) particle size decreases abruptly (~2 nm) as detected by XRD. However, TEM analysis shows the similar particle size (~3.5 nm) irrespective of the cobalt concentration. Local strain in the alloyed nanoparticles with cobalt concentration of 0.18 M increases ~46% in comparison to that of 0.05 M. Direct to indirect energy band-gap transition is obtained when cobalt concentration goes beyond 0.05 M. A red shift in energy band gap is also observed for both the cases. Nanoparticles with low cobalt concentrations were found to have paramagnetic nature with no antiferromagnetic coupling. A negative Curie-Weiss temperature of -75 K with antiferromagnetic coupling was obtained for the high cobalt concentration.
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