Central effects of botulinum toxin type A on spinal cord neurotransmitters and inhibitory neuron markers in rats with local muscular spasticity

Botulinum toksin tip A jedan je od najšire primjenjivanih lijekova u liječenju lokalnih mišićnih hiperkinetičkih poremećaja. Nedavna istraživanja su pokazala mogući terapijski učinak djelovanja BoNT/A na razini centralnih motoneuorna. U ovom radu želimo ispitati ovu hipotezu istražujući učinke BoNT/A na centralnu neurotransmisiju i neuronalne proteinske markere po prvi puta koristeći štakorski model fokalne mišićne hipertonije u istraživanju njegova djelovanja. Štakori su podijeljeni u četiri grupe: kontrolna (vehikulum+fiziološka otopina), TeNT+fiziološka otopina, vehikulum+BoNT/A i TeNT+BoNT/A. Unilateralni mišićni spazam induciran je niskom dozom TeNT im. Farmakološki odgovor na im. i in. injekciju BoNT/A je zabilježen različitim motoričkim parametrima i testovima u svjesnih životinja. Kralježnična moždina štakora je analizirana na koncentracije glutamata i GABA-e ELISA metodom, a ekspresija VAMP-2, SV2C, CGRP i NeuN imunohistokemijski. Rezultati bihevioralnih testova su pokazali da BoNT/A primijenjen i in. i im. smanjuje hipertoniju mišića. Mjerenjem ukupne koncentracije GABA-e i glutamata u tkivu ventralnog roga nije bilo moguće utvrditi potencijalno djelovanje BoNT/A na disbalans inhibicijske i ekscitacijske transmisije. U ventralnom je rogu detektiran pocijepani SNAP-25 nakon primjene BoNT/A i u mišić i u živac, što ukazuje na njegovo moguće centralno djelovanje. Međutim, objašnjenje antispastičkog djelovanja BoNT/A u središnjem živčanom sustavu zahtijeva daljnja istraživanja.Botulinum toxin type A is one of the most widely used drugs in the treatment of local muscular hyperkinetic disorders. Recent studies have demonstrated the possible therapeutic effect of BoNT/A on the central motoneurons. In this paper we want to examine this hypothesis by investigating the effects of BoNT/A on central neurotransmission and neuronal protein markers using a rat model of focal muscle hypertonia. The rats were divided into four groups: control (vehicle + saline), TeNT + saline, vehicle + BoNT/A and TeNT + BoNT/A. Unilateral muscle spasm was induced by a low intramuscular dose of TeNT. The rat spinal cord was analyzed on glutamate and GABA concentrations by ELISA. The expression of VAMP-2, SV2C, CGRP and NeuN proteins was analyzed immunohistochemically. The results of behavioral tests have shown that BoNT/A applied by intraneural and intramuscular route reduces muscle hypertonia. By measuring the total concentration of GABA and glutamate in ventral horn, it was not possible to determine the potential effect of BoNT/A on the inhibitory and excitatory transmission mismatch. In the ventral horn, cleaved SNAP-25 was detected after administration of BoNT/A in muscle and nerve, indicating its possible central activity. However, an explanation of the antispastic effect of BoNT/A in the central nervous system requires further research

Central effects of botulinum toxin type A on spinal cord neurotransmitters and inhibitory neuron markers in rats with local muscular spasticity

Botulinum toksin tip A jedan je od najšire primjenjivanih lijekova u liječenju lokalnih mišićnih hiperkinetičkih poremećaja. Nedavna istraživanja su pokazala mogući terapijski učinak djelovanja BoNT/A na razini centralnih motoneuorna. U ovom radu želimo ispitati ovu hipotezu istražujući učinke BoNT/A na centralnu neurotransmisiju i neuronalne proteinske markere po prvi puta koristeći štakorski model fokalne mišićne hipertonije u istraživanju njegova djelovanja. Štakori su podijeljeni u četiri grupe: kontrolna (vehikulum+fiziološka otopina), TeNT+fiziološka otopina, vehikulum+BoNT/A i TeNT+BoNT/A. Unilateralni mišićni spazam induciran je niskom dozom TeNT im. Farmakološki odgovor na im. i in. injekciju BoNT/A je zabilježen različitim motoričkim parametrima i testovima u svjesnih životinja. Kralježnična moždina štakora je analizirana na koncentracije glutamata i GABA-e ELISA metodom, a ekspresija VAMP-2, SV2C, CGRP i NeuN imunohistokemijski. Rezultati bihevioralnih testova su pokazali da BoNT/A primijenjen i in. i im. smanjuje hipertoniju mišića. Mjerenjem ukupne koncentracije GABA-e i glutamata u tkivu ventralnog roga nije bilo moguće utvrditi potencijalno djelovanje BoNT/A na disbalans inhibicijske i ekscitacijske transmisije. U ventralnom je rogu detektiran pocijepani SNAP-25 nakon primjene BoNT/A i u mišić i u živac, što ukazuje na njegovo moguće centralno djelovanje. Međutim, objašnjenje antispastičkog djelovanja BoNT/A u središnjem živčanom sustavu zahtijeva daljnja istraživanja.Botulinum toxin type A is one of the most widely used drugs in the treatment of local muscular hyperkinetic disorders. Recent studies have demonstrated the possible therapeutic effect of BoNT/A on the central motoneurons. In this paper we want to examine this hypothesis by investigating the effects of BoNT/A on central neurotransmission and neuronal protein markers using a rat model of focal muscle hypertonia. The rats were divided into four groups: control (vehicle + saline), TeNT + saline, vehicle + BoNT/A and TeNT + BoNT/A. Unilateral muscle spasm was induced by a low intramuscular dose of TeNT. The rat spinal cord was analyzed on glutamate and GABA concentrations by ELISA. The expression of VAMP-2, SV2C, CGRP and NeuN proteins was analyzed immunohistochemically. The results of behavioral tests have shown that BoNT/A applied by intraneural and intramuscular route reduces muscle hypertonia. By measuring the total concentration of GABA and glutamate in ventral horn, it was not possible to determine the potential effect of BoNT/A on the inhibitory and excitatory transmission mismatch. In the ventral horn, cleaved SNAP-25 was detected after administration of BoNT/A in muscle and nerve, indicating its possible central activity. However, an explanation of the antispastic effect of BoNT/A in the central nervous system requires further research

Central effects of botulinum toxin type A on spinal cord neurotransmitters and inhibitory neuron markers in rats with local muscular spasticity

Botulinum toksin tip A jedan je od najšire primjenjivanih lijekova u liječenju lokalnih mišićnih hiperkinetičkih poremećaja. Nedavna istraživanja su pokazala mogući terapijski učinak djelovanja BoNT/A na razini centralnih motoneuorna. U ovom radu želimo ispitati ovu hipotezu istražujući učinke BoNT/A na centralnu neurotransmisiju i neuronalne proteinske markere po prvi puta koristeći štakorski model fokalne mišićne hipertonije u istraživanju njegova djelovanja. Štakori su podijeljeni u četiri grupe: kontrolna (vehikulum+fiziološka otopina), TeNT+fiziološka otopina, vehikulum+BoNT/A i TeNT+BoNT/A. Unilateralni mišićni spazam induciran je niskom dozom TeNT im. Farmakološki odgovor na im. i in. injekciju BoNT/A je zabilježen različitim motoričkim parametrima i testovima u svjesnih životinja. Kralježnična moždina štakora je analizirana na koncentracije glutamata i GABA-e ELISA metodom, a ekspresija VAMP-2, SV2C, CGRP i NeuN imunohistokemijski. Rezultati bihevioralnih testova su pokazali da BoNT/A primijenjen i in. i im. smanjuje hipertoniju mišića. Mjerenjem ukupne koncentracije GABA-e i glutamata u tkivu ventralnog roga nije bilo moguće utvrditi potencijalno djelovanje BoNT/A na disbalans inhibicijske i ekscitacijske transmisije. U ventralnom je rogu detektiran pocijepani SNAP-25 nakon primjene BoNT/A i u mišić i u živac, što ukazuje na njegovo moguće centralno djelovanje. Međutim, objašnjenje antispastičkog djelovanja BoNT/A u središnjem živčanom sustavu zahtijeva daljnja istraživanja.Botulinum toxin type A is one of the most widely used drugs in the treatment of local muscular hyperkinetic disorders. Recent studies have demonstrated the possible therapeutic effect of BoNT/A on the central motoneurons. In this paper we want to examine this hypothesis by investigating the effects of BoNT/A on central neurotransmission and neuronal protein markers using a rat model of focal muscle hypertonia. The rats were divided into four groups: control (vehicle + saline), TeNT + saline, vehicle + BoNT/A and TeNT + BoNT/A. Unilateral muscle spasm was induced by a low intramuscular dose of TeNT. The rat spinal cord was analyzed on glutamate and GABA concentrations by ELISA. The expression of VAMP-2, SV2C, CGRP and NeuN proteins was analyzed immunohistochemically. The results of behavioral tests have shown that BoNT/A applied by intraneural and intramuscular route reduces muscle hypertonia. By measuring the total concentration of GABA and glutamate in ventral horn, it was not possible to determine the potential effect of BoNT/A on the inhibitory and excitatory transmission mismatch. In the ventral horn, cleaved SNAP-25 was detected after administration of BoNT/A in muscle and nerve, indicating its possible central activity. However, an explanation of the antispastic effect of BoNT/A in the central nervous system requires further research

Proton pump inhibitors use prior to COVID-19 hospitalization is associated with higher C lostridioides difficile infection rate

Background: There are uncertainties regarding associations of prior proton pump inhibitor (PPI) use with susceptibility for COVID-19 and risks associated with SARS-CoV-2 infection. We aimed to evaluate the associations of prior PPI use with outcomes in hospitalized patients with COVID-19. Research design and methods: We have retrospectively evaluated a total of 5959 consecutively hospitalized patients with COVID-19 from a tertiary-level institution in the period 3/2020-6/2021. Associations of prior PPI use with outcomes of in-hospital mortality, mechanical ventilation, intensive care unit stay, venous thromboembolism, arterial thrombosis, major bleeding, bacteremia, and Clostridioides difficile infection (C. diff.) were evaluated in entire and case-matched cohorts. Results: Among 5959 evaluated patients, there were 1967 (33%) PPI users. In an entire cohort, prior PPI use was associated with higher in-hospital mortality and higher occurrence of C. diff. Association of prior PPI use with mortality diminished, whereas association with C. diff. persisted after multivariable adjustments. In a matched cohort, prior PPI use was associated only with higher risk of C. diff. but not other outcomes in line with multivariable analysis. Conclusions: Although prior PPI use might not have a significant impact on clinical course and mortality of SARS-CoV-2 infection, it may predispose patients to the development of complications like higher occurrence of C. diff. and thus substantially impact the course of treatment

Survival after hospital discharge in patients hospitalized for acute coronavirus disease 2019: data on 2586 patients from a tertiary center registry

Aim: To assess the long-term survival after hospital discharge of patients hospitalized due to coronavirus disease 2019 (COVID-19). ----- Methods: We retrospectively reviewed data on post-discharge survival of 2586 COVID-19 patients hospitalized in our tertiary hospital from March 2020 to March 2021. ----- Results: Among 2586 patients, 1446 (55.9%) were men. The median age was 70 years, interquartile range (IQR, 60-80). The median Charlson comorbidity index was 4 points, IQR (2-5). The median length of hospital stay was 10 days, IQR (7-16). During a median follow-up of 4 months, 192 (7.4%) patients died. The median survival time after hospital discharge was not reached, and 3-month, 6-month, and 12-month survival rates were 93%, 92%, and 91%, respectively. In a multivariate analysis, mutually independent predictors of worse mortality after hospital discharge were age >75 years, Eastern Cooperative Oncology Group status 4, white blood cell count >7 ×109/L, red cell distribution width >14%, urea on admission >10.5 mmol/L, mechanical ventilation during hospital stay, readmission after discharge, absence of obesity, presence of chronic obstructive pulmonary disease, dementia, and metastatic malignancy (P<0.05 for all). ----- Conclusion: Substantial risk of death persists after hospital admission due to COVID-19. Factors related to an increased risk are older age, higher functional impairment, need for mechanical ventilation during hospital admission, parameters indicating more pronounced inflammation, impaired renal function, and particular comorbidities. Interventions aimed at improving patients' functional capacity may be needed

Prevalence and Prognostic Impact of Deranged Liver Blood Tests in COVID-19: Experience from the Regional COVID-19 Center over the Cohort of 3812 Hospitalized Patients

Background: Derangement of liver blood tests (LBT) is frequent in patients with Coronavirus disease 2019 (COVID-19). We aimed to evaluate (a) the prevalence of deranged LBT as well as their association with (b) clinical severity at admission and (c) 30-day outcomes among the hospitalized patients with COVID-19. ----- Methods: Consecutive patients with COVID-19 hospitalized in the regional referral center over the 12-month period were included. Clinical severity of COVID-19 at hospital admission and 30-day outcomes (need for intensive care, mechanical ventilation, or death) were analyzed. ----- Results: Derangement of LBT occurred in 2854/3812 (74.9%) of patients, most frequently due to elevation of AST (61.6%), GGT (46.1%) and ALT (33.4%). Elevated AST, ALT, GGT and low albumin were associated with more severe disease at admission. However, in multivariate Cox regression analysis, when adjusted for age, sex, obesity and presence of chronic liver disease, only AST remained associated with the risk of dying (HR 1.5081 and 2.1315, for elevations 1–3 × ULN and >3 × ULN, respectively) independently of comorbidity burden and COVID-19 severity at admission. Patients with more severe liver injury more frequently experienced defined adverse outcomes. ----- Conclusions: Deranged LBTs are common among patients hospitalized with COVID-19 and might be used as predictors of adverse clinical outcomes