Placebos and painkillers: is mind as real as matter?

Considerable progress has been made in our understanding of the neurobiological mechanisms of the placebo effect, and most of our knowledge originates from the field of pain and analgesia. Today, the placebo effect represents a promising model that could allow us to shed new light on mind-body interactions. The mental events induced by placebo administration can activate mechanisms that are similar to those activated by drugs, which indicates a similarity between psychosocial and pharmacodynamic effects. These new neurobiological advances are already changing our conception of how clinical trials and medical practice must be viewed and conducted.     

Pollen as food and medicine—A review

Pollen, the male gametophyte of flowering plants, is a high energy material, which is collected by insects and stored as food reserve. Pollen has been used traditionally by humans for religious purposes and as supplementary food. Pollen is a concentrated, energy and vitamin rich food that in contemporary times is not only consumed as a dietary component, but also is used in alternative medical treatments. Pollen has potential imporiance as a supplementary and survival food, and for conditioning of athletes. Pollen has been used medically in prostatitis, bleeding stomach ulcers and some infectious diseases, although such use has been questioned by the medical profession. Pollen may also be used for treatment and prevention of the high-altitude-sickness syndrome. Because some individuals are allergic to pollen, and various pollen species contain specific allergens, individual sensitivities must be tested before pollen is used as a treatment or as a supplementary food.     

Amino acids and β-aminopropionitrile as inhibitors of seed germination and growth

The germination of lettuce fruits and legume seeds was affected by the imbibition of solutions of certain amino acids. Seedling growth was inhibited more markedly than germination by these compounds. Non-protein amino acids were, as a group, more effective inhibitors of germination and seedling growth than were protein amino acids, with the exception of lysine. Anomalous results were obtained with β-aminopropionitrile.     

γ-Hydroxyethyl piperidine iminosugar and N-alkylated derivatives: A study of their activity as glycosidase inhibitors and as immunosuppressive agents

An efficient and practical strategy for the synthesis of (3R,4s,5S)-4-(2-hydroxyethyl) piperidine-3,4,5-triol and its N-alkyl derivatives 8a–f, starting from the d-glucose, is reported. The chiral pool methodology involves preparation of the C-3-allyl-α-d-ribofuranodialdose 10, which was converted to the C-5-amino derivative 11 by reductive amination. The presence of C-3-allyl group gives an easy access to the requisite hydroxyethyl substituted compound 13. Intramolecular reductive aminocyclization of C-5 amino group with C-1 aldehyde provided the γ-hydroxyethyl substituted piperidine iminosugar 8a that was N-alkylated to get N-alkyl derivatives 8b–f. Iminosugars 8a–f were screened against glycosidase enzymes. Amongst synthetic N-alkylated iminosugars, 8b and 8c were found to be α-galactosidase inhibitors while 8d and 8e were selective and moderate α-mannosidase inhibitors. In addition, immunomodulatory activity of compounds 8a–f was examined. These results were substantiated by molecular docking studies using AUTODOCK 4.2 programme.     

A study of structure–activity relationship and anion-controlled quinolinyl Ag(I) complexes as antimicrobial and antioxidant agents as well as their interaction with macromolecules

BioMetals - In this communication, we feature the synthesis and in-depth characterization of a series of silver(I) complexes obtained from the complexation of quinolin-4-yl Schiff base ligands...     

Phytoconstituents of Selaginella effusa Alston and Their α-Glucosidase as well as Urease Inhibitory Activities

Three new compounds ( 1 – 2 , 14 ), as well as 22 known compounds ( 3 – 13 , 15 – 25 ), were extracted for the first time from the Selaginella effusa Alston (S. effusa). For the unknown compounds, the planar configurations were determined via NMR and by high-resolution mass spectrometry, while their absolute configurations were determined by calculated electronic circular dichroism (ECD), and the configuration of the stereogenic center of biflavones 4 – 5 were established for the first time. The pure compounds ( 1 – 25 ) were tested in vitro to determine the inhibitory activity of the enzyme-catalyzed reactions. Compounds 1 – 9 inhibited α-glucosidase with IC₅₀ values ranging from 0.30±0.02 to 4.65±0.04 μM and kinetic analysis of enzyme inhibition indicated that biflavones 1 – 3 were mixed-type α-glucosidase inhibitors. Compounds 12 – 13 showed excellent inhibitory activity against urease, with compound 12 (IC₅₀=4.38±0.31 μM) showing better inhibitory activity than the positive control drug AHA (IC₅₀13.52±0.61 μM). In addition, molecular docking techniques were used to simulate inhibitor-enzyme binding and to estimate the binding posture of the α-glucosidase and urease catalytic sites.     

Synthesis and SAR of tetrahydroisoquinolines as Rev-erbα agonists

The design and synthesis of a novel series of Rev-erbα agonists is described. The development and optimization of the tetrahydroisoquinoline series was carried out from an earlier acyclic series of Rev-erbα agonists. Through the optimization of the scaffold 1, several potent compounds with good in vivo profiles were discovered.     

Diet as prophylaxis and treatment for venous thromboembolism?

Background

Both prophylaxis and treatment of venous thromboembolism (VTE: deep venous thrombosis (DVT) and pulmonary emboli (PE)) with anticoagulants are associated with significant risks of major and fatal hemorrhage. Anticoagulation treatment of VTE has been the standard of care in the USA since before 1962 when the U.S. Food and Drug Administration began requiring randomized controlled clinical trials (RCTs) showing efficacy, so efficacy trials were never required for FDA approval. In clinical trials of 'high VTE risk' surgical patients before the 1980s, anticoagulant prophylaxis was clearly beneficial (fatal pulmonary emboli (FPE) without anticoagulants = 0.99%, FPE with anticoagulants = 0.31%). However, observational studies and RCTs of 'high VTE risk' surgical patients from the 1980s until 2010 show that FPE deaths without anticoagulants are about one-fourth the rate that occurs during prophylaxis with anticoagulants (FPE without anticoagulants = 0.023%, FPE while receiving anticoagulant prophylaxis = 0.10%). Additionally, an FPE rate of about 0.012% (35/28,400) in patients receiving prophylactic anticoagulants can be attributed to 'rebound hypercoagulation' in the two months after stopping anticoagulants. Alternatives to anticoagulant prophylaxis should be explored.

Methods and Findings

The literature concerning dietary influences on VTE incidence was reviewed. Hypotheses concerning the etiology of VTE were critiqued in relationship to the rationale for dietary versus anticoagulant approaches to prophylaxis and treatment. Epidemiological evidence suggests that a diet with ample fruits and vegetables and little meat may substantially reduce the risk of VTE; vegetarian, vegan, or Mediterranean diets favorably affect serum markers of hemostasis and inflammation. The valve cusp hypoxia hypothesis of DVT/VTE etiology is consistent with the development of VTE being affected directly or indirectly by diet. However, it is less consistent with the rationale of using anticoagulants as VTE prophylaxis. For both prophylaxis and treatment of VTE, we propose RCTs comparing standard anticoagulation with low VTE risk diets, and we discuss the statistical considerations for an example of such a trial.

Conclusions

Because of (a) the risks of biochemical anticoagulation as anti-VTE prophylaxis or treatment, (b) the lack of placebo-controlled efficacy data supporting anticoagulant treatment of VTE, (c) dramatically reduced hospital-acquired FPE incidence in surgical patients without anticoagulant prophylaxis from 1980 - 2010 relative to the 1960s and 1970s, and (d) evidence that VTE incidence and outcomes may be influenced by diet, randomized controlled non-inferiority clinical trials are proposed to compare standard anticoagulant treatment with potentially low VTE risk diets. We call upon the U. S. National Institutes of Health and the U.K. National Institute for Health and Clinical Excellence to design and fund those trials.     

Cyanidin and cyanidin 3-O-β-D-glucoside as DNA cleavage protectors and antioxidants

Anthocyanins, colored flavonoids, are water-soluble pigments present in the plant kingdom; in fact they are secondary plant metabolites responsible for the blue, purple, and red color of many plant tissues. Present in beans, fruits, vegetables and red wines, considerable amounts of anthocyanins are ingested as constituents of the human diet (180-215 mg daily). There is now increasing interest in the in vivo protective function of natural antioxidants contained in dietary plants against oxidative damage caused by free radical species. Recently, the antioxidant activity of phenolic phytochemicals, has been investigated. Since the antioxidant mechanism of anthocyanin pigments is still controversial, in the present study we evaluated the effects of cyanidin and cyanidin 3-O-beta-D-glucoside on DNA cleavage, on their free radical scavenging capacity and on xanthine oxidase activity. Cyanidin and cyanidin 3-O-beta-D-glucoside showed a protective effect on DNA cleavage, a dose-dependent free radical scavenging activity and significant inhibition of XO activity. These effects suggest that anthocyanins exhibit interesting antioxidant properties, and could therefore represent a promising class of compounds useful in the treatment of pathologies where free radical production plays a key role.     

Aquatic insects and water quality in Peñas Blancas watershed and reservoir

The aquatic insects have been used to evaluate water quality of aquatic environments. The population of aquatic insects and the water quality of the area were characterized according to the natural and human alterations present in the study site. During the monthly-survey, pH, DO, temperature, water level, DBO, PO4 and NO3 were measured. Biological indexes (abundance, species richness and the BMWP-CR) were used to evaluate the water quality. No relation between environmental and aquatic insects was detected. Temporal and spatial differences attributed to the flow events (temporal) and the presence of Pe?as Blancas reservoir (spatial). In the future, the investigations in Pe?as Blancas watershed need to be focused on determining the real influence of the flows, sediment release and the possible water quality degradation because of agriculture activities.     

Are amoxycillin and folate inhibitors as effective as other antibiotics for acute sinusitis? A meta-analysis

Objectives: To examine whether antibiotics are indicated in treating uncomplicated acute sinusitis and, if so, whether newer and more expensive antibiotics with broad spectra of antimicrobial activity are more effective than amoxycillin or folate inhibitors. Design: Meta-analysis of randomised trials. Setting: Outpatient clinics. Subjects: 2717 patients with acute sinusitis or acute exacerbation of chronic sinusitis from 27 trials. Interventions: Any antibiotic versus placebo; amoxycillin or folate inhibitors versus newer, more expensive antibiotics. Main outcome measurements: Clinical failures and cures. Results: Compared with placebo, antibiotics decreased the incidence of clinical failures by half (risk ratio 0.54 (95% confidence interval 0.37 to 0.79)). Risk of clinical failure among 1553 randomised patients was not meaningfully decreased with more expensive antibiotics as compared with amoxycillin (risk ratio 0.86 (0.62 to 1.19); risk difference 0.9 fewer failures per 100 patients (1.4 more failures to 3.1 fewer failures per 100 patients)). The results were similar for other antibiotics versus folate inhibitors (risk ratio 1.01 (0.52 to 1.97)), but data were sparse (n=410) and of low quality. Conclusions: Amoxycillin and folate inhibitors are essentially as effective as more expensive antibiotics for the initial treatment of uncomplicated acute sinusitis. Small differences in efficacy may exist, but are unlikely to be clinically important.

Key messages

• A major question in managing acute sinusitis is whether antibiotics should be used, and if so which drugs should be chosen
• In a comprehensive meta-analysis we evaluated evidence from randomised controlled trials comparing, firstly, antibiotics against placebo and, secondly, amoxycillin and folate inhibitors against newer, more expensive antibiotics
• Antibiotics were significantly more efficacious than placebo in achieving cure of clinical symptoms, but over two thirds of placebo patients showed spontaneous resolution or improvement of symptoms
• Amoxycillin and folate inhibitors had overall similar efficacy compared with newer antibiotics
• The current evidence does not justify the use of expensive, broad spectrum antibiotics in the community for treating uncomplicated acute sinusitis

     

Oat β-glucan and xylan hydrolysates as selective substrates for Bifidobacterium and Lactobacillus strains

Novel oligomers that resist digestion in the upper gut were prepared from oat mixed-linked β-glucan and xylan by enzymatic hydrolysis with lichenase of Bacillus subtilis and xylanase of Trichoderma reesei respectively. The low-molecular-mass hydrolysis products of β-glucan and xylan were compared with fructooligomers and raffinose in their ability to provide growth substrates for probiotic (Lactobacillus and Bifidobacterium) and intestinal (Bacteroides, Clostridium and Escherichia coli) strains in vitro. A degradation profile of each carbohydrate and total sugar consumption were analysed with HPLC, and bacterial growth rate with an automatic turbidometer, the Bioscreen C system. β-Glucooligomers and xylooligomers both enhanced the growth of health-promoting probiotic strains as compared with intestinal bacterial growth, but not to a significant level. Raffinose stimulated the probiotic strains significantly, whereas fructooligomers induced high average growth for intestinal bacteria also. Received: 16 May 1997 / Received revision: 12 September 1997 / Accepted: 19 September 1997     

Enzymatic synthesis of propyl-α-glycosides and their application as emulsifying and antibacterial agents

Alkyl glycosides have been effectively used in many industries because of their biodegradable, emulsification and antibacterial properties. In this study, the alkyl glycoside of propyl glycosides (PG_n) was synthesized using β-cyclodextrin (β-CD) and 1-propanol through the transglycosylation reaction of recombinant cyclodextrin glycosyltransferase (CGTase) from the Bacillus circulans A11. The optimal condition for the synthesis of propyl glycosides consisted of an incubation of 1.5% (w/v) β-CD and 500 U/mL of CGTase in a water/propanol content containing 10% (v/v) 1-propanol at pH 6.0, 50°C for 96 h. Upon analysis of the product at the optimal condition by TLC, at least three products which move faster than glucose were observed. These transferred products were formed with molecular weights of 222.1, 384.1 and 546.4 daltons as determined by mass spectrometry analysis; these values were in accordance with propyl glucoside (PG₁), propyl maltoside (PG₂) and propyl maltotrioside (PG₃), respectively. PG₁ and PG₂ were produced and prepared on a large scale and subsequently purified by preparative TLC. The combined ¹H- and ¹³C-NMR analysis confirmed that the structures of PG₁ and PG₂ were propyl-α-D-glucopyranoside and propyl-α-D-maltopyranoside, respectively. Both PG₁ and PG₂ showed emulsification activity and stability in their formation in water and n-hexadecane. Furthermore, the antibacterial activity of both products was determined and it was found that PG₂ had a higher antibacterial activity against Staphylococcus aureus and Escherichia coli than that of PG₁.     

Streptomyces as symbionts: an emerging and widespread theme?

Streptomyces bacteria are ubiquitous in soil, conferring the characteristic earthy smell, and they have an important ecological role in the turnover of organic material. More recently, a new picture has begun to emerge in which streptomycetes are not in all cases simply free-living soil bacteria but have also evolved to live in symbiosis with plants, fungi and animals. Furthermore, much of the chemical diversity of secondary metabolites produced by Streptomyces species has most likely evolved as a direct result of their interactions with other organisms. Here we review what is currently known about the role of streptomycetes as symbionts with fungi, plants and animals. These interactions can be parasitic, as is the case for scab-causing streptomycetes, which infect plants, and the Streptomyces species Streptomyces somaliensis and Streptomyces sudanensis that infect humans. However, in most cases they are beneficial and growth promoting, as is the case with many insects, plants and marine animals that use streptomycete-produced antibiotics to protect themselves against infection. This is an exciting and newly emerging field of research that will become increasingly important as the search for new antibiotics switches to unusual and under-explored environments.     

Immucillins as Antibiotics for T‐Cell Proliferation and Malaria

The genetic deficiency of human PNP causes a specific immunodeficiency by inducing apoptosis in dividing T‐cells. Powerful inhibitors of PNP have been designed from the experimental determination of the transition state structure of PNPs. The Immucillins are transition state analogue inhibitors with K _d values as low as 7 pM. In the presence of deoxyguanosine the Immucillins kill activated human T‐cells but not other cell types. The Immucillins are orally available and of low toxicity to mice. Immucillins also inhibit PNP from Plasmodium falciparum. Parasites cultured in human erythrocytes are killed by purine starvation in the presence of Immucillins and can be rescued by hypoxanthine.     

Professional burnout as the state and process--what to do?

The professional staff in human service institutions is often required to spend time in intense involvement with other people. Frequently, the staff-client interaction is centred around the client's current problems (psychological, social, and/ or physical) and is therefore charged with feelings of anger, embarrassment, fear or despair In this article we follow the burnout which could not be only the consequence of such job characteristics but could appear also as the result of type of work organization, social relationships, and some bodies personal characteristics as life style, too. Moreover, it can be a consequence of a disturbed balance between give and take at all three levels of social exchange--at interpersonal, at the team, and at the organizational level. So burnout is not only the problem of individuals but also the problem of social environment in which they work. The workplaces shape how people interact with another and how they carry out their jobs. In addition, we try to find the ways how to prevent or to reduce burnout, too. So we present the theories of social comparison (Festinger, 1954; Schachter, 1959), equity theory (Walster and Berscheid, 1978), as also the Kahn's model of employee engagement (1990) and the Schaufeli- Buunk's integrative comprehensive social exchange model (1993) as the possible key to help individuals and organization. In this context V. also Frankl's logo therapy (sense of purpose, 1960) became much more important as the theories of positive (Seligman, 2000) and humanistic psychology (Maslow, 1971, 1987; Rogers, 1959), too.     

Peptides and peptidomimetics as regulators of protein–protein interactions

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Docking and SAR studies of D- and L-isofagomine isomers as human β-glucocerebrosidase inhibitors

We report the structure-activity relationship of a series of D-, and L-isofagomine and fagomine isomers as glycosidase inhibitors. Our study revealed that a positive charge at the anomeric position of d-isofagomines enhanced the potency toward β-glycosidases, while the epimerization at the C3 OH group drastically reduced their inhibitory potency by over three orders of magnitude. Furthermore, d-3,4-di-epi-isofagomine abolished their inhibition activities against all enzymes. L-Isofagomine was also a fairly potent inhibitor of human β-glucocerebrosidase, with an IC?? value of 8.7 μM. A molecular docking study revealed that the positions and orientations of the piperidine ring of D-3-epi-isofagomine in the binding site was similar to that of D-isofagomine, while D-3-epi-isofagomine missed the hydrogen bond interactions between Asp127 and the 3-OH group and between Trp179 and the 3-OH group. Furthermore, the top 10 docking models ranked by IFDscore suggested that D-3,4-di-epi-isofagomine can not bind to β-glucocerebrosidase at a stable interaction mode. These results provide an insight into the structural requirements of isofagomine isomers for developing a new type of pharmacological chaperone for Gaucher disease.     

Design and characterization of electrochemical dopamine–aptamer as convenient and integrated sensing platform

Here, an ultrasensitive label-free electrochemical aptasensor was developed for dopamine (DA) detection. Construction of the aptasensor was carried out by electrodeposition of gold–platinum nanoparticles (Au–PtNPs) on glassy carbon (GC) electrode modified with acid-oxidized carbon nanotubes (CNTs–COOH). A designed complementary amine-capped capture probe (ssDNA1) was immobilized at the surface of PtNPs/CNTs–COOH/GC electrode through the covalent amide bonds formed by the carboxyl groups on the nanotubes and the amino groups on the oligonucleotides. DA-specific aptamer was attached onto the electrode surface through hybridization with the ssDNA1. Methylene blue (MB) was used as an electrochemical indicator that was intercalated into the aptamer through the specific interaction with its guanine bases. In the presence of DA, the interaction between aptamer and DA displaced the MB from the electrode surface, rendering a lowered electrochemical signal attributed to a decreased amount of adsorbed MB. This phenomenon can be applied for DA detection. The peak current of probe (MB) linearly decreased over a DA concentration range of 1–30 nM with a detection limit of 0.22 nM.     

Feruloyl Esterases as Biotechnological Tools： Current and Future Perspectives

Feruloyl esterases represent a diverse group of hydrolases catalyzing the cleavage and formation of ester bonds between plant cell wall polysaccharide and phenolic acid. They are widely distributed in plants and microorganisms. Besides lipases, a considerable number of microbial feruloyl esterases have also been discovered and overexpressed. This review summarizes the latest research on their classification, production, and biophysicochemical properties. Special emphasis is given to the importance of that type of enzyme and their related phenolic ferulic acid compound in biotechnological processes, and industrial and medicinal applications.