Telomerase - future drug target enzyme?

Problem pomnoževanja koncev evkariontskih kromosomov (telomer) so uspešno rešili z odkritjem encima telomeraze konec 80. let prejšnjega stoletja, za odkritje so leta 2009 podelili tudi Nobelovo nagrado za medicino in fiziologijo. Izražanje telomeraze pri rakavih boleznih in človeške sanje o večni mladosti so močno pospešile razvoj farmakoloških telomeraznih inhibitorjev in aktivatorjev, vendar pa kljub 15-letnemu raziskovanju zdravila še niso dostopna na trgu. V članku smo glede na podatke v svetovnih medijih in literaturi naredili pregled farmakoloških učinkovin v zgodnjih fazah kliničnih preskušanj, ki specifično uravnavajo aktivnost telomeraze. Načrtovana protitumorska zdravila večinoma ne bodo namenjena samostojni uporabi, saj telomerazne inhibitorje klinično preskušajo v kombinaciji z obstoječimi kemoterapevtskimi sredstvi, protitelomerazna cepiva pa v kombinaciji z imunostimulansi. Poleg raka in staranja v prispevku navajamo ostala bolezenska stanja, ki so povezana s telomerazo/telomerami, hkrati pa opisujemo tudi tehnično-pravne probleme pri razvoju novih zdravil. Glede na dinamiko razvoja lahko prva protitelomerazna zdravila na trgu pričakujemo v naslednjih petih letih.Eucaryotic chromosome endings (telomeres) replication problem was solved in the 1980\u27s by discovery of the telomerase enzyme. The Nobel Prize in Physiology or Medicine was awarded in 2009 for the discovery of telomerase. Altered telomerase expression in cancer, and human dream of eternal youth haveaccelerated the development of pharmacological telomerase inhibitors and activators. However, after 15 years of development they are still not available on the market. In the present article we reviewed pharmacological agents that target telomerase activity, which have entered clinical trials. Current drugs in development are mostly not intended to be used alone, as telomerase inhibitors under clinical trials are used in combination with the existing chemotherapeutics and anti-telomerase vaccines in combination with immuno-stimulants. Apart from cancer and aging, there are other diseases linked to deregulated activity of telomerasežtelomeres and we also discuss technical and legal problems that researchers encounter in developing anti-telomerase therapy. Given the pace of development, first anti-telomerase drugs might appear on the market in the next 5 years

1943-10-05, Larry to Ann

https://digitalcommons.chapman.edu/avolk_correspondence/1001/thumbnail.jp

1943-09-16, Phillip to Ann

https://digitalcommons.chapman.edu/avolk_correspondence/1000/thumbnail.jp

Classification of subsystems for graded-local nets with trivial superselection structure

We classify Haag-dual Poincar\'e covariant subsystems \B\subset \F of a graded-local net \F on 4D Minkowski spacetime which satisfies standard assumptions and has trivial superselection structure. The result applies to the canonical field net \F_\A of a net \A of local observables satisfying natural assumptions. As a consequence, provided that it has no nontrivial internal symmetries, such an observable net \A is generated by (the abstract versions of) the local energy-momentum tensor density and the observable local gauge currents which appear in the algebraic formulation of the quantum Noether theorem. Moreover, for a net \A of local observables as above, we also classify the Poincar\'e covariant local extensions \B \supset \A which preserve the dynamics.Comment: 38 pages, LaTe

News from the Virasoro algebra

It is shown that the local quantum field theory of the chiral energy- momentum tensor with central charge $c=1$ coincides with the gauge invariant subtheory of the chiral $SU(2)$ current algebra at level 1, where the gauge group is the global $SU(2)$ symmetry. At higher level, the same scheme gives rise to $W$-algebra extensions of the Virasoro algebra.Comment: 4 pages, Latex, DESY 93-11

Quarks, gluons, colour: Facts or fiction?

A general method is presented which allows one to determine from the local gauge invariant observables of a quantum field theory the underlying particle and symmetry structures appearing at the lower (ultraviolet) end of the spatio--temporal scale. Particles which are confined to small scales, i.e., do not appear in the physical spectrum, can be uncovered in this way without taking recourse to gauge fields or indefinite metric spaces. In this way notions such as quark, gluon, colour symmetry and confinement acquire a new and intrinsic meaning which is stable under gauge or duality transformations. The method is illustrated by the example of the Schwinger model.Comment: 22 pages, ams-latex; the article had to be replaced because of tex problems, there are no changes in the tex

Conveyor design optimization as the provision of sustainability

Konvejeri su strojevi koji u principu rade neprekidno tijekom dugih vremenskih perioda. Čak i malo povećanje energetske učinkovitosti dovodi do znatnih ušteda energije, dakle do bolje održivosti. Energija se troši na svladavanje disipativnih učinaka i moguće podizanje transportiranih roba. Može se uštedjeti jedino smanjenjem disipativnih učinaka. U radu se daje primjer dviju konstrukcija lančanog konvejera proizvodnog stroja. Utvrđen je učinak promjena konstrukcije na potrošnju energije. Disipativni učinci definiraju se primjenom analitičkog pristupa verificiranog mjerenjima. Dokazana je i obrazložena poboljšana održivost u slučaju druge konstrukcije.Conveyors are machines which typically operate continuously during long periods of time. Even a small increase in energy efficiency leads toward considerable energy savings and therefore improved sustainability. The energy is consumed to overcome dissipative effects and for possible lifting of transported goods. It can be saved only by reducing the dissipative effects. In the paper an example is introduced of two designs of the production machine chain conveyor. The effect of the changes of the design on the energy consumption is established. The dissipative effects are defined using analytical approach which is verified by means of measurements. Improved sustainability in the case of the second design is proven and discussed

Health professionals' knowledge of probiotics : an international survey

The objective of this study was to survey health professionals to investigate their knowledge of probiotics. An online survey was conducted to gather data on the knowledge of health professionals. The online survey was distributed via email and social media platforms using snowball sampling. A total of 1066 health professionals (859; 80.6% female) from 30 countries responded to the survey. Most of the respondents evaluated their knowledge of probiotics as medium (36.4%) or good (36.2%). Only 8.9% of the respondents rated it as excellent. No statistical difference in knowledge was found between male and female health professionals. Over 80% of pharmacists, allied health professionals, medical doctors and dentists, and other health professionals knew the correct definition of probiotics as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”, whereas three quarters of registered nurses and midwives and less than two thirds of psychologists identified the correct definition. Statistically, more female than male health professionals knew the correct definition of probiotics. The most frequently recognized species of bacteria containing probiotic strains were Lactobacillus acidophilus (92%), Bifidobacterium bifidum (82%), and Lactobacillus rhamnosus (62%). The opinions on when it is best to take probiotics were different (χ2 = 28.375; p < 0.001), with 90.2% of respondents identifying that probiotics have beneficial effects if taken during antibiotic therapy, 83.5% for diarrhea, 70.6% for constipation, 63.3% before traveling abroad, and 60.4% for treating allergies. Almost 79% of health professionals involved in this study have advised their patients to use probiotics and 57.5% of the respondents wanted to learn more about probiotics. All things considered, health professionals have a medium level of knowledge of probiotics, which could be improved by the implementation of targeted learning programs. As probiotics have many beneficial effects in a wide range of health areas, health professionals need to adopt the use of probiotics in clinical practice