Deciphering the scopolamine challenge rat model by preclinical functional MRI

AbstractDuring preclinical drug testing, the systemic administration scopolamine (SCO), a cholinergic antagonist, is widely used. However, it has limited predictive validity partly due to its peripheral side-effects. Therefore, objective neuroimaging measures would enhance its translational value. To this end, in Wistar rats, we measured whisker-stimulation induced functional MRI activation after SCO, peripherally acting butylscopolamine (BSCO), or saline administration. Besides the commonly used gradient-echo echo-planar imaging (GE EPI), we also used an arterial spin labeling method in isoflurane anesthesia. With the GE EPI measurement, SCO decreased the evoked BOLD response in the barrel cortex (BC), while BSCO increased it in the anterior cingulate cortex. In a second experiment, we used GE EPI and spin-echo (SE) EPI sequences in a combined (isoflurane + i.p. dexmedetomidine) anesthesia to account for anesthesia-effects. Here, we also examined the effect of donepezil. In the combined anesthesia, with the GE EPI, SCO decreased the activation in the BC and the inferior colliculus (IC). BSCO reduced the response merely in the IC. Our results revealed that SCO attenuated the evoked BOLD activation in the BC as a probable central effect in both experiments. The likely peripheral vascular actions of SCO with the given fMRI sequences depended on the type of anesthesia or its dose.Significance StatementRodent functional MRI (fMRI) is a powerful and promising tool for translational research, as it bridges the gap between animal experiments and human neuroimaging. Scopolamine (SCO) is a standard reference drug for inducing experimental cognitive impairment in both animals and humans, however, it has limited predictive validity partly due to its peripheral side-effects. We measured whisker-stimulation induced fMRI activation after injecting SCO or its peripherally acting analog with different fMRI sequences in two different anesthesia type and analyzed the data with different statistical inferences. We deciphered that the likely peripheral vascular actions of SCO with the given fMRI sequences depended on the type of anesthesia or its dose.

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Deciphering the scopolamine challenge rat model by preclinical functional MRI

Scientific Reports ◽

10.1038/s41598-021-90273-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Gergely Somogyi ◽

Dávid Hlatky ◽

Tamás Spisák ◽

Zsófia Spisák ◽

Gabriella Nyitrai ◽

...

Keyword(s):

Functional Mri ◽

Drug Testing ◽

Barrel Cortex ◽

Spin Echo ◽

Anterior Cingulate ◽

Planar Imaging ◽

Saline Administration ◽

Combined Anesthesia ◽

Echo Planar ◽

Labeling Method

AbstractDuring preclinical drug testing, the systemic administration of scopolamine (SCO), a cholinergic antagonist, is widely used. However, it suffers important limitations, like non-specific behavioural effects partly due to its peripheral side-effects. Therefore, neuroimaging measures would enhance its translational value. To this end, in Wistar rats, we measured whisker-stimulation induced functional MRI activation after SCO, peripherally acting butylscopolamine (BSCO), or saline administration in a cross-over design. Besides the commonly used gradient-echo echo-planar imaging (GE EPI), we also used an arterial spin labeling method in isoflurane anesthesia. With the GE EPI measurement, SCO decreased the evoked BOLD response in the barrel cortex (BC), while BSCO increased it in the anterior cingulate cortex. In a second experiment, we used GE EPI and spin-echo (SE) EPI sequences in a combined (isoflurane + i.p. dexmedetomidine) anesthesia to account for anesthesia-effects. Here, we also examined the effect of donepezil. In the combined anesthesia, with the GE EPI, SCO decreased the activation in the BC and the inferior colliculus (IC). BSCO reduced the response merely in the IC. Our results revealed that SCO attenuated the evoked BOLD activation in the BC as a probable central effect in both experiments. The likely peripheral vascular actions of SCO with the given fMRI sequences depended on the type of anesthesia or its dose.

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Pilot Study: Quantitative Photoacoustic Evaluation of Peripheral Vascular Dynamics Induced by Carfilzomib In Vivo

Sensors ◽

10.3390/s21030836 ◽

2021 ◽

Vol 21 (3) ◽

pp. 836

Author(s):

Thi Thao Mai ◽

Manh-Cuong Vo ◽

Tan-Huy Chu ◽

Jin Young Kim ◽

Chulhong Kim ◽

...

Keyword(s):

Pilot Study ◽

Side Effects ◽

Cardiovascular Events ◽

Evaluation Method ◽

Vascular System ◽

Maximum Amplitude ◽

Peripheral Vascular ◽

Peripheral Vasculature ◽

Mouse Ear

Carfilzomib is mainly used to treat multiple myeloma. Several side effects have been reported in patients treated with carfilzomib, especially those associated with cardiovascular events, such as hypertension, congestive heart failure, and coronary artery disease. However, the side effects, especially the manifestation of cardiovascular events through capillaries, have not been fully investigated. Here, we performed a pilot experiment to monitor peripheral vascular dynamics in a mouse ear under the effects of carfilzomib using a quantitative photoacoustic vascular evaluation method. Before and after injecting the carfilzomib, bortezomib, and PBS solutions, we acquired high-resolution three-dimensional PAM data of the peripheral vasculature of the mouse ear during each experiment for 10 h. Then, the PAM maximum amplitude projection (MAP) images and five quantitative vascular parameters, i.e., photoacoustic (PA) signal, diameter, density, length fraction, and fractal dimension, were estimated. Quantitative results showed that carfilzomib induces a strong effect on the peripheral vascular system through a significant increase in all vascular parameters up to 50%, especially during the first 30 min after injection. Meanwhile, bortezomib and PBS do not have much impact on the peripheral vascular system. This pilot study verified PAM as a comprehensive method to investigate peripheral vasculature, along with the effects of carfilzomib. Therefore, we expect that PAM may be useful to predict cardiovascular events caused by carfilzomib.

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Olfactory modulation of barrel cortex activity during active whisking and passive whisker stimulation

10.21203/rs.3.rs-289925/v1 ◽

2021 ◽

Author(s):

Anthony Renard ◽

Evan Harrell ◽

Brice Bathallier

Keyword(s):

Facial Nerve ◽

Calcium Imaging ◽

Tactile Stimulation ◽

Barrel Cortex ◽

Neuronal Responses ◽

Population Activity ◽

Tactile Information ◽

Large Populations ◽

Whisker Stimulation ◽

The Impact

Abstract Rodents depend on olfaction and touch to meet many of their fundamental needs. The joint significance of these sensory systems is underscored by an intricate coupling between sniffing and whisking. However, the impact of simultaneous olfactory and tactile inputs on sensory representations in the cortex remains elusive. To study these interactions, we recorded large populations of barrel cortex neurons using 2-photon calcium imaging in head-fixed mice during olfactory and tactile stimulation. We find that odors alter barrel cortex activity in at least two ways, first by enhancing whisking, and second by central cross-talk that persists after whisking is abolished by facial nerve sectioning. Odors can either enhance or suppress barrel cortex neuronal responses, and while odor identity can be decoded from population activity, it does not interfere with the tactile representation. Thus, barrel cortex represents olfactory information which, in the absence of learned associations, is coded independently of tactile information.

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Synthesis, Characterization and Acute Anti-inflammatory Evaluation of New Mefenamic Acid Derivatives Having 4-Thiazolidinone Nucleus

Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) ◽

10.31351/vol28iss1pp138-146 ◽

2019 ◽

Vol 28 (1) ◽

pp. 138-146

Author(s):

Mustafa H. Ali Alsafi ◽

Muthanna S. Farhan

Keyword(s):

Side Effects ◽

Mefenamic Acid ◽

Paw Edema ◽

Compound I ◽

Reference Drug ◽

Cox 2 ◽

Anti Inflammatory ◽

Derivatives Of ◽

Cox 1 ◽

Inflammatory Effect

Mefenamic acid (MA) is one of the non-steroidal anti-inflammatory drugs, it is widely used probably due to having both anti-inflammatory and analgesic activity, the main side effects of mefenamic acid include gastrointestinal tract (GIT) disturbance mainly diarrhea, peptic ulceration, and gastric bleeding. The analgesic effects of NSAIDs are probably linked to COX-2 inhibition, while COX-1 inhibition is the major cause of this classic adverse effects. Introduction of thiazolidinone may lead to the increase in the bulkiness leads to the preferential inhibition of COX-2 rather than COX-1 enzyme. The study aimed to synthesize derivatives of mefenamic acid with more potency and to decrease the drug's potential side effects, new series of 4-thiazolidinone derivatives of mefenamic acid were synthesized IVa-g. The synthetic procedures for target compounds and their intermediates are designed to be as follows: acylation of secondary amine of mefenamic acid by chloroacetylchloride to produce compound (I), then reaction between compound (I) and hydrazine hydrate to form hydrazine derivative of mefenamic acid (compound II). After that, Schiff base formation by addition of seven benzaldehyde derivatives and finally, cyclization in presence of thioglycolic acid to form 4-thiazolidinone heterocyclic ring. The characterization of the titled compounds has been established on the basis of their spectral FTIR, 1HNMR data, and by measurements of their physical properties. In vivo acute anti-inflammatory effect of the synthesized compounds was evaluated in rats using egg-white induced edema model of inflammation. The tested compounds and the reference drug produced significant reduction of paw edema with respect to the effect of dimethyl sulfoxide 10%v/v (control group). Compound IVe showed more potent effect than mefenamic acid at 240-300 min, while at time 300 min, compounds IVa and IVd exhibit more potent anti-inflammatory effect than mefenamic acid (50mg/kg, i.p.) as they reduced paw edema significantly more than mefenamic acid at mentioned intervals (p<0.05) . On the other hand compound IVc exhibited lower anti-inflammatory effect.

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Response and Side Effects from Rheumatoid Arthritis Therapy at Dr. Soetomo General Hospital Surabaya 2017

JUXTA: Jurnal Ilmiah Mahasiswa Kedokteran Universitas Airlangga ◽

10.20473/juxta.v13i12022.9-12 ◽

2022 ◽

Vol 13 (1) ◽

pp. 9

Author(s):

Ayu Imamatun Nisa ◽

Awalia Awalia ◽

Jusak Nugraha

Keyword(s):

Rheumatoid Arthritis ◽

Side Effects ◽

General Hospital ◽

Clinical Symptoms ◽

Laboratory Data ◽

Kidney Injury ◽

Cross Sectional ◽

Reactive Protein ◽

Cross Sectional Design ◽

The Given

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease which mainly attacks synovial membrane and causes systemic manifestation. During treatment, controlling disease activity is needed to prevent further complication. On the other hand, medications used in the treatment of RA may bring various side effects. It is important to evaluate side effects from the given therapy.Methods: This study aimed to evaluate response and side effects of therapy in RA patients. The samples were collected from 59 RA patients at Rheumatology Division of Outpatient Clinic in Department of Internal Medicine Dr. Soetomo General Hospital Surabaya in 2017. This study method was descriptive observational with cross sectional design using medical records.Results: Pain was reduced in 83.1% patients, Erythrocyte Sedimentation Rate (ESR) increased in 61.4% patients, and C-Reactive Protein (CRP) decreased in 50% patients. Based on the statistic analysis, ESR decreased significantly (p = 0.012) while CRP decreased not significantly (p = 0.415). The side effects were observed from clinical and laboratory data. Based on clinical symptoms, there were alopecia in 1.7% patient, dyspepsia in 78% patients, infection in 27.1% patients, and other symptoms including itchy skin, neuropathy, hyperuricemia, hyperkalemia and Acute Kidney Injury (AKI). Meanwhile, abnormalities in laboratory data include increased aspartate transaminase (AST) in 3.8% patients, increased alanine transaminase (ALT) in 26.1% patients, increased Blood Urea Nitrogen (BUN) in 7.9% patients, increased creatinine serum in 7.9% patients, decreased hemoglobin in 15.5% patients, and decreased leukocytes in 3.4% patients.Conclusion: Most patients had a good therapeutic response based on decreased pain, while ESR had a significant decrease and CRP did not have significant decrease. Side effects discovered in patients were various

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Antiartherosclerotic Effects of Plant Flavonoids

BioMed Research International ◽

10.1155/2014/480258 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 80

Author(s):

Shamala Salvamani ◽

Baskaran Gunasekaran ◽

Noor Azmi Shaharuddin ◽

Siti Aqlima Ahmad ◽

Mohd Yunus Shukor

Keyword(s):

Cardiovascular Diseases ◽

Side Effects ◽

Animal Models ◽

Vascular Diseases ◽

Lipid Lowering ◽

Peripheral Vascular ◽

Heart Attacks ◽

Synthetic Drug

Atherosclerosis is the process of hardening and narrowing the arteries. Atherosclerosis is generally associated with cardiovascular diseases such as strokes, heart attacks, and peripheral vascular diseases. Since the usage of the synthetic drug, statins, leads to various side effects, the plants flavonoids with antiartherosclerotic activity gained much attention and were proven to reduce the risk of atherosclerosisin vitroandin vivobased on different animal models. The flavonoids compounds also exhibit lipid lowering effects and anti-inflammatory and antiatherogenic properties. The future development of flavonoids-based drugs is believed to provide significant effects on atherosclerosis and its related diseases. This paper discusses the antiatherosclerotic effects of selected plant flavonoids such as quercetin, kaempferol, myricetin, rutin, naringenin, catechin, fisetin, and gossypetin.

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Infragranular barrel cortex activity is enhanced with learning

Journal of Neurophysiology ◽

10.1152/jn.00305.2012 ◽

2012 ◽

Vol 108 (5) ◽

pp. 1278-1287 ◽

Cited By ~ 7

Author(s):

Rebekah L. Ward ◽

Luke C. Flores ◽

John F. Disterhoft

Keyword(s):

Single Unit ◽

Barrel Cortex ◽

Eyeblink Conditioning ◽

Sensory Cortex ◽

Learning Criterion ◽

Extracellular Recordings ◽

Primary Sensory Cortex ◽

Whisker Stimulation ◽

Trace Eyeblink Conditioning

The barrel cortex (BC) is essential for the acquisition of whisker-signaled trace eyeblink conditioning and shows learning-related expansion of the trained barrels after the acquisition of a whisker-signaled task. Most previous research examining the role of the BC in learning has focused on anatomic changes in the layer IV representation of the cortical barrels. We studied single-unit extracellular recordings from individual neurons in layers V and VI of the BC as rabbits acquired the whisker-signaled trace eyeblink conditioning task. Neurons in layers V and VI in both conditioned and pseudoconditioned animals robustly responded to whisker stimulation, but neurons in conditioned animals showed a significant enhancement in responsiveness in concert with learning. Learning-related changes in firing rate occurred as early as the day of learning criterion within the infragranular layers of the primary sensory cortex.

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