Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons

“Molecular neurosurgery” is emerging as a new medical concept, and is the combination of two partners: (i) a molecular neurosurgery agent, and (ii) the cognate receptor whose activation results in the selective elimination of a specific subset of neurons in which this receptor is endogenously expressed. In general, a molecular surgery agent is a selective and potent ligand, and the target is a specific cell type whose elimination is desired through the molecular surgery procedure. These target cells have the highest innate sensitivity to the molecular surgery agent usually due to the highest receptor density being in their plasma membrane. The interaction between the ligand and its receptor evokes an overactivity of the receptor. If the receptor is a ligand-activated non-selective cation channel, the overactivity of receptor leads to excess Ca2+ and Na+ influx into the cell and finally cell death. One of the best known examples of such an interaction is the effect of ultrapotent vanilloids on TRPV1-expressing pain-sensing neurons. One intrathecal resiniferatoxin (RTX) dose allows for the receptor-mediated removal of TRPV1+ neurons from the peripheral nervous system. The TRPV1 receptor-mediated ion influx induces necrotic processes, but only in pain-sensing neurons, and usually within an hour. Besides that, target-specific apoptotic processes are also induced. Thus, as a nano-surgery scalpel, RTX removes the neurons responsible for generating pain and inflammation from the peripheral nervous system providing an option in clinical management for the treatment of morphine-insensitive pain conditions. In the future, the molecular surgery concept can also be exploited in cancer research for selectively targeting the specific tumor cell

Molecular surgery concept from bench to bedside: a focus on TRPV1+ pain-sensing neurons

“Molecular neurosurgery” is emerging as a new medical concept, and is the combination of two partners: (i) a molecular neurosurgery agent, and (ii) the cognate receptor whose activation results in the selective elimination of a specific subset of neurons in which this receptor is endogenously expressed. In general, a molecular surgery agent is a selective and potent ligand, and the target is a specific cell type whose elimination is desired through the molecular surgery procedure. These target cells have the highest innate sensitivity to the molecular surgery agent usually due to the highest receptor density being in their plasma membrane. The interaction between the ligand and its receptor evokes an overactivity of the receptor. If the receptor is a ligand-activated non-selective cation channel, the overactivity of receptor leads to excess Ca2+ and Na+ influx into the cell and finally cell death. One of the best known examples of such an interaction is the effect of ultrapotent vanilloids on TRPV1- expressing pain-sensing neurons. One intrathecal resiniferatoxin (RTX) dose allows for the receptor-mediated removal of TRPV1+ neurons from the peripheral nervous system. The TRPV1 receptor-mediated ion influx induces necrotic processes, but only in pain-sensing neurons, and usually within an hour. Besides that, target-specific apoptotic processes are also induced. Thus, as a nano-surgery scalpel, RTX removes the neurons responsible for generating pain and inflammation from the peripheral nervous system providing an option in clinical management for the treatment of morphine-insensitive pain conditions. In the future, the molecular surgery concept can also be exploited in cancer research for selectively targeting the specific tumor cell

AcrB homológ membrán transzporterek vizsgálata = Investigation of AcrB homologue membrane transporters

Különböző AcrB homológ fehérjéket vizsgáltunk. Kettő a Brucella melitensis baktériumban kódolt (BMEI 1645, BMEI 0895) egy-egy pedig Haemophilus influenzae-ban (HI 0895). Acinetobacter baumannii-ban (ACIAD0783), Pseudomonas aeruginosa-ban (PA0158), Pectobacterium carotovorum-ban (ECA1169), Helicobacter pylori-ban (HP0607), Klebsiella pneumoniae-ban (KPN00443) valamint Bacillus cereus törzsekből: Bacillus cereus ATCC 10987 (BCE 0788), és Bacillus cereus ATCC 14579 (BC0714). Sikeres klónozást a következő gének esetén értünk el: BMEI 1645, BMEI 0895, HI 0895, BCE 0788, BC0714. A felsorolt gének közül a BMEI 1645-ös fehérje over-expresszálódott egyedül Escherichia coliban. Ezt a fehérjét szolubilizáltuk, tisztítottuk affinitás oszlopon, majd gélszűréssel. A fehérje két fő populációt mutatott a gélszűrés eredményként, melyeket jellemeznünk szükséges a fehérje kristályosítása előtt. Az AcrB fehérjét, mint kontrollt, sikeresen klónoztuk, expresszáltuk Escherichia coliban, nagy mennyiségben tisztítottuk és kristályosítottuk. A kristályosítás során ß-peptid foldamerek hatását vizsgáltuk és megállapítottuk, hogy a kristályosítás során segédanyagként használt foldamer megkönnyíteni, lerövidíteni látszik kristályosításhoz szükséges időt. | Different AcrB homologue transporters were examined. Two of them are coded in Brucella melitensis (BMEI 1645, BMEI 0895), one each is coded in Haemophilus influenzae (HI 0895). Acinetobacter baumannii (ACIAD0783), Pseudomonas aeruginosa (PA0158), Pectobacterium carotovorum (ECA1169), Helicobacter pylori (HP0607), Klebsiella pneumoniae (KPN00443) and two of them from different Bacillus cereus strains Bacillus cereus ATCC 10987 (BCE 0788) and Bacillus cereus ATCC 14579 (BC0714). The following genes were successfully cloned: BMEI 1645, BMEI 0895, HI 0895, BCE 0788, BC0714. BMEI 1645 protein was overexpressed in Escherichia coli. The protein was solubilized and purified by affinity chromatography and size exclusion chromatography. Two major populations of protein were observed after size exclusion chromatography and those need to be characterized before protein crystallization. AcrB protein as a control was successfully cloned, expressed in Escherichia coli, purified in large scale and crystallized. The effect of a ß-peptid foldamer was investigated and we determined that the ß-peptid foldamer as a crystallization adjuvant might help to decrease the time necessary for crystal formation

The effects of infrared laser therapy and weightbath traction hydrotherapy in disorders of the lumbar spine: a controlled pilot study with follow-up

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Inventory methods in order to minimize raw materials at the inventory level in the supply chain

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Future challenges and areas of development for supply chain management

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