TY  - JOUR
AU  - Joksimović, Sonja
AU  - Joksimović, Srđan
AU  - Manzella, Francesca
AU  - Asnake, Betelehem
AU  - Orestes, Peihan
AU  - Raol, Yogendra
AU  - Krishnan, Kathiresan
AU  - Covey, Douglas
AU  - Jevtović-Todorović, Vesna
AU  - Todorović, Slobodan
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3610
AB  - Background and Purpose: Neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) is a novel hypnotic and voltage-dependent blocker of T-type calcium channels. Here, we examine its potential analgesic effects and adjuvant anaesthetic properties using a post-surgical pain model in rodents. Experimental Approach: Analgesic properties of 3β-OH were investigated in thermal and mechanical nociceptive tests in sham or surgically incised rats and mice, with drug injected either systemically (intraperitoneal) or locally via intrathecal or intraplantar routes. Hypnotic properties of 3β-OH and its use as an adjuvant anaesthetic in combination with isoflurane were investigated using behavioural experiments and in vivo EEG recordings in adolescent rats. Key Results: A combination of 1% isoflurane with 3β-OH (60 mg·kg−1, i.p.) induced suppression of cortical EEG and stronger thermal and mechanical anti-hyperalgesia during 3 days post-surgery, when compared to isoflurane alone and isoflurane with morphine. 3β-OH exerted prominent enantioselective thermal and mechanical antinociception in healthy rats and reduced T-channel-dependent excitability of primary sensory neurons. Intrathecal injection of 3β-OH alleviated mechanical hyperalgesia, while repeated intraplantar application alleviated both thermal and mechanical hyperalgesia in the rats after incision. Using mouse genetics, we found that CaV3.2 T-calcium channels are important for anti-hyperalgesic effect of 3β-OH and are contributing to its hypnotic effect. Conclusion and Implications: Our study identifies 3β-OH as a novel analgesic for surgical procedures. 3β-OH can be used to reduce T-channel-dependent excitability of peripheral sensory neurons as an adjuvant for induction and maintenance of general anaesthesia while improving analgesia and lowering the amount of volatile anaesthetic needed for surgery.
PB  - John Wiley and Sons Inc.
T2  - British Journal of Pharmacology
T1  - Novel neuroactive steroid with hypnotic and T-type calcium channel blocking properties exerts effective analgesia in a rodent model of post-surgical pain
VL  - 177
IS  - 8
SP  - 1735
EP  - 1753
DO  - 10.1111/bph.14930
ER  - 

@article{
author = "Joksimović, Sonja and Joksimović, Srđan and Manzella, Francesca and Asnake, Betelehem and Orestes, Peihan and Raol, Yogendra and Krishnan, Kathiresan and Covey, Douglas and Jevtović-Todorović, Vesna and Todorović, Slobodan",
year = "2020",
abstract = "Background and Purpose: Neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) is a novel hypnotic and voltage-dependent blocker of T-type calcium channels. Here, we examine its potential analgesic effects and adjuvant anaesthetic properties using a post-surgical pain model in rodents. Experimental Approach: Analgesic properties of 3β-OH were investigated in thermal and mechanical nociceptive tests in sham or surgically incised rats and mice, with drug injected either systemically (intraperitoneal) or locally via intrathecal or intraplantar routes. Hypnotic properties of 3β-OH and its use as an adjuvant anaesthetic in combination with isoflurane were investigated using behavioural experiments and in vivo EEG recordings in adolescent rats. Key Results: A combination of 1% isoflurane with 3β-OH (60 mg·kg−1, i.p.) induced suppression of cortical EEG and stronger thermal and mechanical anti-hyperalgesia during 3 days post-surgery, when compared to isoflurane alone and isoflurane with morphine. 3β-OH exerted prominent enantioselective thermal and mechanical antinociception in healthy rats and reduced T-channel-dependent excitability of primary sensory neurons. Intrathecal injection of 3β-OH alleviated mechanical hyperalgesia, while repeated intraplantar application alleviated both thermal and mechanical hyperalgesia in the rats after incision. Using mouse genetics, we found that CaV3.2 T-calcium channels are important for anti-hyperalgesic effect of 3β-OH and are contributing to its hypnotic effect. Conclusion and Implications: Our study identifies 3β-OH as a novel analgesic for surgical procedures. 3β-OH can be used to reduce T-channel-dependent excitability of peripheral sensory neurons as an adjuvant for induction and maintenance of general anaesthesia while improving analgesia and lowering the amount of volatile anaesthetic needed for surgery.",
publisher = "John Wiley and Sons Inc.",
journal = "British Journal of Pharmacology",
title = "Novel neuroactive steroid with hypnotic and T-type calcium channel blocking properties exerts effective analgesia in a rodent model of post-surgical pain",
volume = "177",
number = "8",
pages = "1735-1753",
doi = "10.1111/bph.14930"
}

Joksimović, S., Joksimović, S., Manzella, F., Asnake, B., Orestes, P., Raol, Y., Krishnan, K., Covey, D., Jevtović-Todorović, V.,& Todorović, S.. (2020). Novel neuroactive steroid with hypnotic and T-type calcium channel blocking properties exerts effective analgesia in a rodent model of post-surgical pain. in British Journal of Pharmacology
John Wiley and Sons Inc.., 177(8), 1735-1753.
https://doi.org/10.1111/bph.14930

Joksimović S, Joksimović S, Manzella F, Asnake B, Orestes P, Raol Y, Krishnan K, Covey D, Jevtović-Todorović V, Todorović S. Novel neuroactive steroid with hypnotic and T-type calcium channel blocking properties exerts effective analgesia in a rodent model of post-surgical pain. in British Journal of Pharmacology. 2020;177(8):1735-1753.
doi:10.1111/bph.14930 .

Joksimović, Sonja, Joksimović, Srđan, Manzella, Francesca, Asnake, Betelehem, Orestes, Peihan, Raol, Yogendra, Krishnan, Kathiresan, Covey, Douglas, Jevtović-Todorović, Vesna, Todorović, Slobodan, "Novel neuroactive steroid with hypnotic and T-type calcium channel blocking properties exerts effective analgesia in a rodent model of post-surgical pain" in British Journal of Pharmacology, 177, no. 8 (2020):1735-1753,
https://doi.org/10.1111/bph.14930 . .

TY  - JOUR
AU  - Stefanović, Tatjana
AU  - Bosić, Srećko
AU  - Vekić, Jelena
AU  - Spasojević-Kalimanovska, Vesna
AU  - Todorović, Vesna
AU  - Pijanović, Marina
AU  - Zeljković, Aleksandra
AU  - Stefanović, Aleksandra
AU  - Jelić-Ivanović, Zorana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3667
AB  - Glikohemoglobin  (HbA1c)  je  važan  parametar  za  praćenje  dugoročne  metaboličke kontrole  i  procenu  rizika  za  razvoj  hroničnih  komplikacija  kod pacijenata  sa  dijabetes melitusom (DM). U ovoj studiji ispitivali smo povezanost postignute metaboličke kontrole u tipu  2  DM  sa  rizikom  za  razvoj  i  primenjenim  modalitetom  lečenja  sindroma  dijabetesnog stopala (SDS). U istraživanju je učestvovalo 111 pacijenata (80 muškaraca i 31 žena) sa tipom 2 DM, starosti 65,5 ± 9,8 godina. Kod 41 pacijenta SDS je lečen neoperativnim (konzervativnim) pristupom, hirurška intervencija manjeg obima (amputacija u predelu stopala) je izvršena kod 41,  a  opsežna  hirurška  intervencija  (amputacija  u  predelu  potkolenice)  kod  29  pacijenata. Koncentracije  biohemijskih  parametara  i  HbA1c  su  određene  standardnim  laboratorijskim metodama. U ispitivanoj grupi najučestaliji faktor rizika za nastanak SDS (82% pacijenata) bila je  neadekvatna  glikoregulacija  (HbA1c>8%).  Utvrdili  smo  da  su  pacijenti  koji  su  lečeni hirurškim putem imali statistički značajno više vrednosti HbA1c u poređenju sa pacijentima koji su  lečeni  neoperativnim  pristupom  (P<0,05).  Ukupan  broj  pacijenata  koji  je  podvrgnut hirurškom  lečenju  bio  je  značajno  veći  u  grupi  sa  neadekvatnom glikoregulacijom  (68,2% pacijenata  sa  neadekvatnom vs.  40%  pacijenata  sa  adekvatnom  glikoregulacijom; P<0,05). Utvrdili smo da je verovatnoća za amputaciju 3,2 puta veća ukoliko pacijent ima neadekvatnu glikoregulaciju  (OR=3,21;  95%CI:1,18-8,69; P<0,05).  Naši  rezultati  su  pokazali  da  se održavanjem dobre metaboličke kontrole u tipu 2 DM smanjuje rizik za razvoj SDS, ali i stepen invazivnosti postupka lečenja SDS.
AB  - Glycosylated hemoglobin (HbA1c) is important parameter for the assessment of long term metabolic control and risk for development of chronic complications in patients with diabetes mellitus (DM). This study investigates associations between achieved metabolic control in type 2 DM with the risk for the development of diabetic foot (DF) and its treatment modalities. The study included 111 patients (80 men and 31 women) with type 2 DM, aged 65.5±9.8 years. In 41 patients DF was treated by a conservative approach, 41 patients underwent a minor limb amputation (foot amputation) and 29 patients underwent a major limb amputation (below-knee amputation).  The  levels  of  HbA1c  and  serum  biochemical  parameters  were  measured  by standard laboratory methods. The most frequent risk factor for DF in the examined group (82% patients) was poor glycaemic control (HbA1c>8%). The level of HbA1c was significantly higher in surgically treated patients than in the conservatively treated group (P<0.05). The number of patients  who  underwent  surgical  treatment  were  significantly  higher  in  the  group  with  poor glycaemic control (62.8% patients with poor glycaemic control vs. 40% patients with optimal glycaemic control; P<0.05). We found that the patients with poor glycaemic control had 3.2 times  higher  risk  for  amputation  (OR=3.21;  95%CI:1.18-8.69; P<0.05).  In  conclusion,  our results  demonstrated  that  optimal  metabolic  control  in  type  2  DM  reduces  the  risk  for  DF development, as well as the invasiveness of DF treatment.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Significance of glycosylated haemoglobin determination for the assessment of lowerextremity amputation risk in patients with diabetic foot
T1  - Značaj određivanja glikohemoglobina u proceni rizika od amputacija kod pacijenata sa sindromom dijabetesnog stopala
VL  - 69
IS  - 2
SP  - 51
EP  - 66
DO  - 10.5937/arhfarm1902051X
ER  - 

@article{
author = "Stefanović, Tatjana and Bosić, Srećko and Vekić, Jelena and Spasojević-Kalimanovska, Vesna and Todorović, Vesna and Pijanović, Marina and Zeljković, Aleksandra and Stefanović, Aleksandra and Jelić-Ivanović, Zorana",
year = "2019",
abstract = "Glikohemoglobin  (HbA1c)  je  važan  parametar  za  praćenje  dugoročne  metaboličke kontrole  i  procenu  rizika  za  razvoj  hroničnih  komplikacija  kod pacijenata  sa  dijabetes melitusom (DM). U ovoj studiji ispitivali smo povezanost postignute metaboličke kontrole u tipu  2  DM  sa  rizikom  za  razvoj  i  primenjenim  modalitetom  lečenja  sindroma  dijabetesnog stopala (SDS). U istraživanju je učestvovalo 111 pacijenata (80 muškaraca i 31 žena) sa tipom 2 DM, starosti 65,5 ± 9,8 godina. Kod 41 pacijenta SDS je lečen neoperativnim (konzervativnim) pristupom, hirurška intervencija manjeg obima (amputacija u predelu stopala) je izvršena kod 41,  a  opsežna  hirurška  intervencija  (amputacija  u  predelu  potkolenice)  kod  29  pacijenata. Koncentracije  biohemijskih  parametara  i  HbA1c  su  određene  standardnim  laboratorijskim metodama. U ispitivanoj grupi najučestaliji faktor rizika za nastanak SDS (82% pacijenata) bila je  neadekvatna  glikoregulacija  (HbA1c>8%).  Utvrdili  smo  da  su  pacijenti  koji  su  lečeni hirurškim putem imali statistički značajno više vrednosti HbA1c u poređenju sa pacijentima koji su  lečeni  neoperativnim  pristupom  (P<0,05).  Ukupan  broj  pacijenata  koji  je  podvrgnut hirurškom  lečenju  bio  je  značajno  veći  u  grupi  sa  neadekvatnom glikoregulacijom  (68,2% pacijenata  sa  neadekvatnom vs.  40%  pacijenata  sa  adekvatnom  glikoregulacijom; P<0,05). Utvrdili smo da je verovatnoća za amputaciju 3,2 puta veća ukoliko pacijent ima neadekvatnu glikoregulaciju  (OR=3,21;  95%CI:1,18-8,69; P<0,05).  Naši  rezultati  su  pokazali  da  se održavanjem dobre metaboličke kontrole u tipu 2 DM smanjuje rizik za razvoj SDS, ali i stepen invazivnosti postupka lečenja SDS., Glycosylated hemoglobin (HbA1c) is important parameter for the assessment of long term metabolic control and risk for development of chronic complications in patients with diabetes mellitus (DM). This study investigates associations between achieved metabolic control in type 2 DM with the risk for the development of diabetic foot (DF) and its treatment modalities. The study included 111 patients (80 men and 31 women) with type 2 DM, aged 65.5±9.8 years. In 41 patients DF was treated by a conservative approach, 41 patients underwent a minor limb amputation (foot amputation) and 29 patients underwent a major limb amputation (below-knee amputation).  The  levels  of  HbA1c  and  serum  biochemical  parameters  were  measured  by standard laboratory methods. The most frequent risk factor for DF in the examined group (82% patients) was poor glycaemic control (HbA1c>8%). The level of HbA1c was significantly higher in surgically treated patients than in the conservatively treated group (P<0.05). The number of patients  who  underwent  surgical  treatment  were  significantly  higher  in  the  group  with  poor glycaemic control (62.8% patients with poor glycaemic control vs. 40% patients with optimal glycaemic control; P<0.05). We found that the patients with poor glycaemic control had 3.2 times  higher  risk  for  amputation  (OR=3.21;  95%CI:1.18-8.69; P<0.05).  In  conclusion,  our results  demonstrated  that  optimal  metabolic  control  in  type  2  DM  reduces  the  risk  for  DF development, as well as the invasiveness of DF treatment.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Significance of glycosylated haemoglobin determination for the assessment of lowerextremity amputation risk in patients with diabetic foot, Značaj određivanja glikohemoglobina u proceni rizika od amputacija kod pacijenata sa sindromom dijabetesnog stopala",
volume = "69",
number = "2",
pages = "51-66",
doi = "10.5937/arhfarm1902051X"
}

Stefanović, T., Bosić, S., Vekić, J., Spasojević-Kalimanovska, V., Todorović, V., Pijanović, M., Zeljković, A., Stefanović, A.,& Jelić-Ivanović, Z.. (2019). Significance of glycosylated haemoglobin determination for the assessment of lowerextremity amputation risk in patients with diabetic foot. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 69(2), 51-66.
https://doi.org/10.5937/arhfarm1902051X

Stefanović T, Bosić S, Vekić J, Spasojević-Kalimanovska V, Todorović V, Pijanović M, Zeljković A, Stefanović A, Jelić-Ivanović Z. Significance of glycosylated haemoglobin determination for the assessment of lowerextremity amputation risk in patients with diabetic foot. in Arhiv za farmaciju. 2019;69(2):51-66.
doi:10.5937/arhfarm1902051X .

Stefanović, Tatjana, Bosić, Srećko, Vekić, Jelena, Spasojević-Kalimanovska, Vesna, Todorović, Vesna, Pijanović, Marina, Zeljković, Aleksandra, Stefanović, Aleksandra, Jelić-Ivanović, Zorana, "Significance of glycosylated haemoglobin determination for the assessment of lowerextremity amputation risk in patients with diabetic foot" in Arhiv za farmaciju, 69, no. 2 (2019):51-66,
https://doi.org/10.5937/arhfarm1902051X . .