The many “faces” of copper in medicine and treatment

Copper (Cu) is an essential microelement found in all living organisms with the unique ability to adopt two different redox states—in the oxidized (Cu²⁺) and reduced (Cu⁺). It is required for survival and serves as an important catalytic cofactor in redox chemistry for proteins that carry out fundamental biological functions, important in growth and development. The deficit of copper can result in impaired energy production, abnormal glucose and cholesterol metabolism, increased oxidative damage, increased tissue iron (Fe) accrual, altered structure and function of circulating blood and immune cells, abnormal neuropeptides synthesis and processing, aberrant cardiac electrophysiology, impaired myocardial contractility, and persistent effects on the neurobehavioral and the immune system. Increased copper level has been found in several disorders like e.g.: Wilson’s disease or Menke’s disease. New findings with the great potential for impact in medicine include the use of copper-lowering therapy for antiangiogenesis, antifibrotic and anti-inflammatory purposes. The role of copper in formation of amyloid plaques in Alzheimer’s disease, and successful treatment of this disorder in rodent model by copper chelating are also of interest. In this work we will try to describe essential aspects of copper in chosen diseases. We will represent the evidence available on adverse effect derived from copper deficiency and copper excess. We will try to review also the copper biomarkers (chosen enzymes) that help reflect the level of copper in the body.     

Characteristics and application of S1–P1 nucleases in biotechnology and medicine

3′–nucleases/nucleotidases of the S1–P1 family (EC 3.1.30.1) are single–strand–specific or non-specific zinc–dependent phosphoesterases present in plants, fungi, protozoan parasites, and in some bacteria. They participate in a wide variety of biological processes and their current biotechnological applications rely on their single–strand preference, nucleotide non-specificity, a broad range of catalytic conditions and high stability. We summarize the present and potential utilization of these enzymes in biotechnology and medicine in the context of their biochemical and structure–function properties. Explanation of unanswered questions for bacterial and trypanosomatid representatives could facilitate development of emerging applications in medicine.     

Genetic and pharmacological evidence of intraneuronal Aβ accumulation in APP transgenic mice

Intraneuronal punctate immunostaining in Alzheimer’s disease brain and amyloid-β precursor protein (APP) transgenic mice has been suggested to represent Aβ, but this is somewhat controversial. Here we show that both biochemical Aβ levels and intraneuronal immunostaining are reduced in APP transgenic mice when γ-secretase is inhibited. Moreover, BACE-1 deficient APP transgenic mice show neither Aβ production nor intraneuronal immunostaining. Our findings suggest that the punctate immunostaining with APP antibodies is due to Aβ that has accumulated inside neurons. Similar type of intraneuronal Aβ accumulation, which precedes senile plaque formation, may link Aβ to tauopathy and neurodegeneration in Alzheimer’s disease pathogenesis.     

The ‘requirement of total evidence’ and its role in phylogenetic systematics

The question of whether or not to partition data for the purposes of inferring phylogenetic hypotheses remains controversial. Opinions have been especially divided since Kluge's (1989, Systematic Zoology 38, 7–25) claim that data partitioning violates the requirement of total evidence (RTE). Unfortunately, advocacy for or against the RTE has not been based on accurate portrayals of the requirement. The RTE is a basic maxim for non-deductive inference, stipulating that evidence must be considered if it has relevance to an inference. Evidence is relevant if it has a positive or negative effect on a given conclusion. In the case of ℈partitioned’ phylogenetic inferences, the RTE is violated, and the basis for rational belief in any conclusion is compromised, unless it is shown that the partitions are evidentially irrelevant to one another. The goal of phylogenetic systematics is to hypothesize past causal conditions to account for observed shared similarities among two or more species. Such inferences are non-deductive, necessitating consideration of the RTE. Some phylogeneticists claim the parsimony criterion as justification for the RTE. There is no relation between the two – parsimony is a relation between a hypothesis and causal question(s). Parsimony does not dictate the content of premises prior to an inference. ℈Taxonomic congruence,’ ℈supertrees,’ and ℈conditional combination’ methods violate the RTE. Taxonomic congruence and supertree methods also fail to achieve the intended goal of phylogenetic inference, such that ℈consensus trees’ and ℈supertrees’ lack an empirical basis. ℈Conditional combination’ is problematic because hypotheses derived from partitioned data cannot be compared – a causal hypothesis inferred to account for a set of effects only has relevance to those effects, not any comparative relevance to other causal hypotheses. A similar problem arises in the comparisons of hypotheses derived from different causal theories.     

Traditional medicine practitioners’ knowledge and views on treatment of pregnant women in three regions of Mali

Background

Despite the widespread use of medicinal plants in Mali, knowledge about how traditional practitioners (TPs) treat pregnant and lactating women is lacking.

Aim of the study

The aim of this study was to investigate how traditional practitioners in Mali treat common diseases and ailments during pregnancy.

Methods

Data was collected through structured interviews of traditional practitioners in one urban (Bamako) and two rural areas (Siby and Dioila) in Mali. The TPs were interviewed about how they treat common diseases and ailments during pregnancy. They were also asked to name harmful plants in pregnancy and plants that could affect breast milk production. In addition, we asked about nine specific medicinal plants commonly used in Mali; Opilia amentacea (syn. Opilia celtidifolia), Ximenia americana, Cola cordifolia, Combretum glutinosum, Parkia biglobosa, Trichilia emetica, Combretum micranthum, Lippia chevalieri and Vepris heterophylla.

Results

A total of 72 traditional practitioners (64% women, age: 34 to 90 years) were interviewed during an eight week period October 2011 to December 2011. They treated between 1 and 30 pregnant women with medicinal plants per months. We found a relatively high consensus for treatment of pregnant women with common diseases and ailments like nausea and dermatitis. The highest informer consensus was found for the treatment of malaria during pregnancy. TPs generally recommended pregnant women to avoid medicinal plants with bitter tastes like stem and root bark of Khaya senegalensis and Opilia amentacea (syn. Opilia celtidifolia). TPs distinguished between oral (potentially unsafe) and dermal use (safe) of Opilia amentacea (syn. Opilia celtidifolia). Cola cordifolia was used to facilitate labor.

Conclusion

Experience and knowledge about treatment of pregnant women with medicinal plants was broad among the traditional practitioners in the three investigated regions in Mali. Collaborating with traditional practitioners on the safe use of medicinal plants in pregnancy may promote safer pregnancies and better health for mothers and their unborn infants in Mali.

     

Forecasting Helicoverpa populations in Australia： A comparison of regression based models and a bioclimatic based modelling approach

Abstract Long-term forecasts of pest pressure are central to the effective management of many agricultural insect pests. In the eastern cropping regions of Australia, serious infestations of Helicoverpa punctigera (Wallengren) and H. armigera (Hübner)(Lepidoptera: Noctuidae) are experienced annually. Regression analyses of a long series of light-trap catches of adult moths were used to describe the seasonal dynamics of both species. The size of the spring generation in eastern cropping zones could be related to rainfall in putative source areas in inland Australia. Subsequent generations could be related to the abundance of various crops in agricultural areas, rainfall and the magnitude of the spring population peak. As rainfall figured prominently as a predictor variable, and can itself be predicted using the Southern Oscillation Index (SOI), trap catches were also related to this variable. The geographic distribution of each species was modelled in relation to climate and CLIMEX was used to predict temporal variation in abundance at given putative source sites in inland Australia using historical meteorological data. These predictions were then correlated with subsequent pest abundance data in a major cropping region. The regression-based and bioclimatic-based approaches to predicting pest abundance are compared and their utility in predicting and interpreting pest dynamics are discussed.     

Electromagnetic fields in medicine – The state of art

ABSTRACT

Introduction: Intense development of methods belonging to physical medicine has been noted recently. There are treatment methods, which in many cases lead to reduction treatment time and positively influence on quality of life treatment patients. Research implications: The present physical medicine systematically extends their therapeutic possibilities. This above applies to illnesses and injuries of locomotor system, diseases affecting of soft tissues, as well as chronic wounds. The aim of the study: The evidence on this are the results of basic and clinical examinations relating the practical use of electromagnetic fields in medicine. Originality: In this work the authors introduced the procedure using the current knowledge relating to physical characteristic and biological effects of the magnetic fields. In the work the following methods were used: static magnetic fields, spatial magnetic fields, the variable magnetic fields both with laser therapy (magnetolaserotherapy) and variable magnetic fields both with light optical non-laser (magnetoledtherapy) talked.     

Is there evidence of learned helplessness in horses?

Learned helplessness is a psychological condition whereby individuals learn that they have no control over unpleasant or harmful conditions, that their actions are futile, and that they are helpless. In a series of experiments in which dogs were exposed to inescapable shocks, this lack of control subsequently interfered with the ability to learn an avoidance task. There is evidence that both neural adaptations and behavioral despair occur in response to uncontrollable aversive experiences in rodents, although this has yet to be demonstrated in other species such as horses. However, certain traditional methods of horse training and some behavioral modification techniques--it has been suggested--may involve aversive conditions over which the horse has little or no control. When training and management procedures are repeatedly unpleasant for the horse and there is no clear association between behavior and outcome, this is likely to interfere with learning and performance-in addition to compromising welfare. This article reviews published literature and anecdotal evidence to explore the possibility that the phenomenon, learned helplessness, occurs in the horse.     

A review of MHC‐based mate preferences and fostering experiments in two congenic strains of mice

We review our studies of mate choice with two MHC‐congenic strains of mice. This work was stimulated by findings from Yamazaki and colleagues showing that male mice exhibited mate preferences for females whose MHC‐haplotype was different from their own, while female mice exhibited either no preference or a weak preference for males of a particular MHC‐haplotype (see Beauchamp et al., 1988). Since these findings were unexpected (mate choice theory predicts that females will be more selective than males), we studied the preferences of mice from two additional MHC‐congenic strains to assess the generality of the previous findings. Specifically, the goals of our research were: (1) to determine the mate preferences of congenic mice with MHC‐haplotypes derived from wild populations, (2) to compare the mate preferences of male and female mice in a test situation where each sex has a clear opportunity to make a choice, and (3) to estimate effects of cross‐fostering on each sex. This revised version was published online in July 2006 with corrections to the Cover Date.     

Molecular evidence for the hybridity ofIlex × wandoensis and the phylogenetic study of KoreanIlex based on ITS sequence data

In this study, internal transcribed spacer (ITS) regions within the nuclear ribosomal DNA of KoreanIlex were analyzed in order to investigate any molecular evidence thatI. × wandoensis could serve as a putative hybrid betweenI. cornuta andI. integra. We also sought to clearly identify taxonomic relationships and problems caused by consecutive external morphological characters among taxa in the genus. We sequenced 20 clones fromI. × wandoensis and found these individuals displayed intra-genomic polymorphisms within ITS regions. The analysis of the clones clearly demonstrated the presence of discrete sequences from bothI. cornuta andI. integra, thereby confirmingI. × wandoensis is a species that was formed by crossingI. cornuta andI. integra. Lastly, the subgenusIlex, which contains the evergreen species, failed to form a monophyletic group in a strict consensus tree that was prepared based upon ITS regions.I. crenata var.microphylla in the subgenus KoreaIlex, which has presented taxonomic problems previously, formed an independent clade within the consensus tree, thereby showing distinction fromI. crenata.) Genetic discontinuity ofI. macropoda andI. Macropoda for.pseudo-macropoda individuals couldn't be confirmed.     

Structure and property based design, synthesis and biological evaluation of γ-lactam based HDAC inhibitors

Histone deacetylases (HDACs) are involved in post-translational modification and gene expression. Cancer cells recruited amounts of HDACs for their survival by epi-genetic down regulation of tumor suppressor genes. HDACs have been the promising targets for treatment of cancer, and many HDAC inhibitors have been investigated nowadays. In previous study, we synthesized δ-lactam core HDAC inhibitors which showed potent HDAC inhibitory activities as well as cancer cell growth inhibitory activities. Through QSAR study of the δ-lactam based inhibitors, the smaller core is suggested as more active than larger one because it fits better in narrow hydrophobic tunnel of the active pocket of HDAC enzyme. The smaller γ-lactam core HDAC inhibitors were designed and synthesized for biological and property optimization. Phenyl, naphthyl and thiophenyl groups were introduced as the cap groups. Hydrophobic and bulky cap groups increase potency of HDAC inhibition because of hydrophobic interaction between HDAC and inhibitors. In overall, γ-lactam based HDAC inhibitors showed more potent than δ-lactam analogues.