Human CYP1B1 Leu432Val gene polymorphism: ethnic distribution in African-Americans, Caucasians and Chinese; oestradiol hydroxylase activity; and distribution in prostate cancer cases and controls

Cytochrome P4501B1 (CYP1B1) is involved in the activation of many carcinogens and in the metabolism of steroid hormones, including 17beta-oestradiol (E2) and testosterone. We report a significant difference in the allele frequencies of two point mutations in the coding region of the CYP1B1 gene among Caucasian (n = 189), African-American (n = 52) and Chinese (Linxian) (n = 109) populations. A (C to G) transversion at position 1666 in exon 3, which results in an amino acid substitution of Leu432 to Val, was present in African-Americans with an allele frequency for Va1432 of 0.75, in Caucasians of 0.43, and in Chinese of 0.17. A (C to T) transition at position 1719 in exon 3, with no amino acid change (Asp449), appeared to be closely linked with the Val432 variant. Results using human lung microsomal preparations from individuals with the CYP1B1Val/Val and CYP1B1Leu/Leu genotypes indicate that Val432 variant may be a high activity allele and thus may contribute to the interindividual differences in CYP1B1 activity. Because CYP1B1 is involved in hormone and carcinogen metabolism, and given the disparate rates of prostate cancer among ethnic groups, we also evaluated the association of the CYP1B1 Leu432Val polymorphism with prostate cancer risk in a pilot case-control study. Among Caucasians, 34% of men with cancer (n = 50) were homozygous for the Val432 polymorphism, while only 12% of matched control subjects (n = 50) had this genotype. These preliminary data indicate that genetic polymorphisms in CYP1B1 might play an important role in human prostate carcinogenesis.     

Nutritional care and candidates for small bowel transplantation

Twenty two children were evaluated for small bowel transplantation between 1989 and 1994. Eight were unfit for transplantation and died within three months; a raised plasma bilirubin concentration (> 200 mumol/l) predicted death from liver failure within six months (p = 0.0001). The 11 children who were not managed by a multidisciplinary nutritional care team were less well nourished at referral, had more complications with intravenous feeding catheters, and greater early mortality while awaiting transplantation (p < 0.05). It is recommended that children with chronic intestinal failure be referred for assessment early, before liver dysfunction is established.     

Immunophenotype and Ultrastructural Studies in Blast Crisis of Chronic Myeloid Leukemia

Thirty-four patients with chronic myeloid leukemia in blast crisis (CML-BC) were evaluated for lineage differentiation, with immunological markers and the presence of ultrastructural peroxidase. Eighteen (52.9%) were found to have myeloid blast crisis. Cytochemically, myeloperoxidase (MPO) could bedetectedonly in six patientson light microscopy while in the remaining 12 patients, myeloid differentiation was confirmed only by demonstration of MPO either at ultrastructural level or by the reactivity with anti myeloperoxidase (anti MPO) antibody. Six (17.6%) had lymphoid blast crisis as identified by lymphoid specific markers (CD 19; CD 10; CD7; CD4) along with the absence of myeloid markers. Heterogenous blast cell populations with mixed lineage differentiation were seen in 4 (I I .7%) patients. These cases showed both lymphoid (CD 19, CD 10) and myeloid (anti MPO and ultrastructural MPO) characteristics. A single case of megakaryoblastic blast crisis was identitied with positivity for CD41 and CD42 along with the presence of platelet peroxidase at the ultrastructural level. Five cases (148) of CML blast crisis remained unclassifiable. These results suggest that blast crisis in CML show an arrest of differentiation at an early stage when compared to de novo acute leukemias. This is particularly evident from the fact that MPO could only be demonstrated ultra-StNCtIIrally or with anti MPO antibody in the majority of patients with myeloid differentiation. It is expected that utilisation of molecular studies including immunoglobulin and T-cell receptor gene rearrangement and m-RNA expression for myeloperoxidase will provide a better insight into the level of differentiation for the presently unclassifiable cases of CML-blast crisis.     

Development of a 384-well colorimetric assay to quantify hydrogen peroxide generated by the redox cycling of compounds in the presence of reducing agents

We report here the development and optimization of a simple 384-well colorimetric assay to measure H(2)O(2) generated by the redox cycling of compounds incubated with reducing agents in high-throughput screening (HTS) assay buffers. The phenol red-horseradish peroxidase (HRP) assay readily detected H(2)O(2) either added exogenously or generated by the redox cycling of compounds in dithiothreitol (DTT). The generation of H(2)O(2) was dependent on the concentration of both the compound and DTT and was abolished by catalase. Although both DTT and tris(2-carboxyethyl) phosphine sustain the redox cycling generation of H(2)O(2) by a model quinolinedione, 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5,8-dione (NSC 663284; DA3003-1), other reducing agents such as beta-mercaptoethanol, glutathione, and cysteine do not. The assay is compatible with HTS. Once terminated, the assay signal was stable for at least 5 h, allowing for a reasonable throughput. The assay tolerated up to 20% dimethyl sulfoxide, allowing a wide range of compound concentrations to be tested. The assay signal window was robust and reproducible with average Z-factors of > or =0.8, and the redox cycling generation of H(2)O(2) by DA3003-1 in DTT exhibited an average 50% effective concentration of 0.830 +/- 0.068 microM. Five of the mitogen-activated protein kinase phosphatase (MKP) 1 inhibitors identified in an HTS were shown to generate H(2)O(2) in the presence of DTT, and their inhibition of MKP-1 activity was shown to be time dependent and was abolished or significantly reduced by either 100 U of catalase or by higher DTT levels. A cross-target query of the PubChem database with three structurally related pyrimidotriazinediones revealed active flags in 36-39% of the primary screening assays. Activity was confirmed against a number of targets containing active site cysteines, including protein tyrosine phosphatases, cathepsins, and caspases, as well as a number of cellular cytotoxicity assays. Rather than utilize resources to conduct a hit characterization effort involving several secondary assays, the phenol red-HRP assay provides a simple, rapid, sensitive, and inexpensive method to identify compounds that redox cycle in DTT or tris(2-carboxyethyl)phosphine to produce H(2)O(2) that may indirectly modulate target activity and represent promiscuous false-positives from a primary screen.     

Development of a validated RP-LC/ESI-MS-MS method for separation, identification and determination of related substances of tamsulosin in bulk drugs and formulations

A reversed-phase high performance liquid chromatographic (RP-HPLC) method for evaluation of purity of tamsulosin in bulk drugs and pharmaceuticals was developed. The separation was accomplished on an Inertsil C(18) column using 10 mM ammonium acetate: acetonitrile as a mobile phase in a gradient elution mode. A photodiode array detector set at 280 nm was used for detection. The impurities were identified by ESI-MS-MS. The detection limits were 0.06-0.11 microg/ml. The method was validated with respect to accuracy, precision, linearity, ruggedness and limits of detection and quantification. It finds application not only for monitoring the reactions during the process development but also on quality assurance of tamsulosin.     

Meningitis due to Rhodotorula glutinis in an HIV infected patient

Rhodotorula spp, though considered a common saprophyte, recently has been reported as causative agent of opportunistic mycoses. We present a case of meningitis in an immunocompromised human immunodeficiency virus infected patient who presented with longstanding fever. He was diagnosed as a case of chronic meningitis. Diagnosis was confirmed by cell cytology, India ink preparation, Gram staining and culture of cerebrospinal fluid (CSF) sample. CSF culture grew Rhodotorula glutinis. Therapy with amphotericin B was successful in eliminating the yeast from CSF and the patient was discharged after recovery.     

Effect of fibre-reinforced composite as a post-obturation restorative material on fracture resistance of endodontically treated teeth: A systematic review

BackgroundFracture resistance of endodontically treated tooth is affected due to large cavity designs and access cavities and an appropriate material capable to resist fracture plays an important role. This review aims to evaluate the effect of fibre-reinforced composite (FRC) as a post-obturation material on fracture resistance of endodontically treated teeth.ObjectivesTo systematically gather and evaluate the fracture resistance of fibre-reinforced composite as a post-obturation restorative material in endodontically treated teeth.Data SourcesA systematic search was conducted using PubMed, Ebsco Host, Scopus, Google Scholar, Hinari and manual search library resources from 1st Jan 2000 to 30th November 2019 to identify appropriate studies.ResultA total of 157 articles were examined out of which 55 articles were selected after reading the title. After removing the duplicates, 27 articles were screened for abstract and 1 article was eliminated as it did not meet the eligibility criteria. A thorough reading of the full text of the remaining 26 selected articles was assessed for eligibility. Amongst these, 1 article was then excluded from the study as the full text was not accessible. Lastly, 25 articles were included in the study.ConclusionFRC as a core material increases fracture resistance of endodontically treated teeth but they do not have the fracture resistance similar to the intact tooth. Both polyethylene and short fibre-reinforced composites showed greater fracture resistance when compared to glass FRC and restoration without reinforcement. Also, the fracture resistance increases if restored with FRC along with retention slots and are placed on the occlusal third surfaces of cavities. Also, favourable fractures were most commonly seen and it usually occurred at the level of enamel and dentin and adhesive fractures were seen.     

Glutamate acting at NMDA receptors stimulates embryonic cortical neuronal migration

During cortical development, embryonic neurons migrate from germinal zones near the ventricle into the cortical plate, where they organize into layers. Mechanisms that direct neuronal migration may include molecules that act as chemoattractants. In rats, GABA, which localizes near the target destination for migrating cortical neurons, stimulates embryonic neuronal migration in vitro. In mice, glutamate is highly localized near the target destinations for migrating cortical neurons. Glutamate-induced migration of murine embryonic cortical cells was evaluated in cell dissociates and cortical slice cultures. In dissociates, the chemotropic effects of glutamate were 10-fold greater than the effects of GABA, demonstrating that for murine cortical cells, glutamate is a more potent chemoattractant than GABA. Thus, cortical chemoattractants appear to differ between species. Micromolar glutamate stimulated neuronal chemotaxis that was mimicked by microM NMDA but not by other ionotropic glutamate receptor agonists (AMPA, kainate, quisqualate). Responding cells were primarily derived from immature cortical regions [ventricular zone (vz)/subventricular zone (svz)]. Bromodeoxyuridine (BrdU) pulse labeling of cortical slices cultured in NMDA antagonists (microM MK801 or APV) revealed that antagonist exposure blocked the migration of BrdU-positive cells from the vz/svz into the cortical plate. PCR confirmed the presence of NMDA receptor expression in vz/svz cells, whereas electrophysiology and Ca2+ imaging demonstrated that vz/svz cells exhibited physiological responses to NMDA. These studies indicate that, in mice, glutamate may serve as a chemoattractant for neurons in the developing cortex, signaling cells to migrate into the cortical plate via NMDA receptor activation.     

Emerging cold plasma treatment and machine learning prospects for seed priming: a step towards sustainable food production

Seeds are vulnerable to physical and biological stresses during the germination process. Seed priming strategies can alleviate such stresses. Seed priming is a technique of treating and drying seeds prior to germination in order to accelerate the metabolic process of germination. Multiple benefits are offered by seed priming techniques, such as reducing fertilizer use, accelerating seed germination, and inducing systemic resistance in plants, which are both cost-effective and eco-friendly. For seed priming, cold plasma (CP)-mediated priming could be an innovative alternative to synthetic chemical treatments. CP priming is an eco-friendly, safe and economical, yet relatively less explored technique towards the development of seed priming. In this review, we discussed in detail the application of CP technology for seed priming to enhance germination, the quality of seeds, and the production of crops in a sustainable manner. Additionally, the combination treatment of CP with nanoparticle (NP) priming is also discussed. The large numbers of parameters need to be monitored and optimized during CP treatment to achieve the desired priming results. Here, we discussed a new perspective of machine learning for modeling plasma treatment parameters in agriculture for the development of synergistic protocols for different types of seed priming.

The perspective of machine learning for modeling plasma treatment parameters in agriculture for the development of synergistic protocols for different types of seed priming.     

Self-reported health assessments in the 2002 World Health Survey: how do they correlate with education?

Objective

To assess the value of self-rated health assessments by examining the association between education and self-rated poor health.

Methods

We used the globally representative population-based sample from the 2002 World Health Survey, composed of 219 713 men and women aged 25 and over in 69 countries, to examine the association between education and self-rated poor health. In a binary regression model with a logit link function, we used self-rated poor health as the binary dependent variable, and age, sex and education as the independent variables.

Findings

Globally, there was an inverse association between years of schooling and self-rated poor health (odds ratio, OR: 0.929; 95% confidence interval, CI: 0.926–0.933). Compared with the individuals in the highest quintile of years of schooling, those in the lowest quintile were twice as likely to report poor health (OR: 2.292; 95% CI: 2.165–2.426). We found a dose–response relationship between quintiles of years of schooling and the ORs for reporting poor health. This association was consistent among men and women; low-, middle- and high-income countries; and regions.

Conclusion

Our findings suggest that self-reports of health may be useful for epidemiological investigations within countries, even in low-income settings.