Objective
Much evidence suggests that the subiculum plays a significant role in the regulation of epileptic activity. Lactate acts as a neuroprotective agent against many conditions that cause brain ...damage. During epileptic seizures, lactate formation reaches up to ~6 mmol/L in the brain. We investigated the effect of lactate on subicular pyramidal neurons after induction of epileptiform activity using 4‐aminopyridine (4‐AP‐0Mg2+) in an in vitro epilepsy model in rats. The signaling mechanism associated with the suppression of epileptiform discharges by lactate was also investigated.
Methods
We used patch clamp electrophysiology recordings on rat subicular neurons of acute hippocampal slices. Immunohistochemistry was used for demonstrating the expression of hydroxycarboxylic acid receptor 1 (HCA1) in the subiculum.
Results
Our study showed that application of 6 mmol/L lactate after induction of epileptiform activity reduced spike frequency (control 2.5 ± 1.23 Hz vs lactate 1.01 ± 0.91 Hz, P = .049) and hyperpolarized the subicular neurons (control −51.8 ± 1.9 mV vs lactate −57.2 ± 3.56 mV, P = .002) in whole cell patch‐clamp experiments. After confirming the expression of HCA1 in subicular neurons, we demonstrated that lactate‐mediated effect occurs via HCA1 by using its specific agonist. All values are mean ±SD. Electrophysiological recordings revealed the involvement of Gβγ and intracellular cAMP in the lactate‐induced effect. Furthermore, current‐clamp and voltage‐clamp experiments showed that the G protein–coupled inwardly rectifying potassium (GIRK) channel blocker tertiapin‐Q, negated the lactate‐induced inhibitory effect, which confirmed that lactate application results in outward GIRK current.
Significance
Our finding points toward the potential role of lactate as an anticonvulsant by showing lactate‐induced suppression of epileptiform activity in subicular neurons. The study gives a different insight by suggesting importance of endogenous metabolite and associated signaling factors, which can aid in improving the present therapeutic approach for treating epilepsy.
One health approach and COVID-19: A perspective Jorwal, Pooja; Bharadwaj, Swati; Jorwal, Pankaj
Journal of family medicine and primary care,
12/2020, Letnik:
9, Številka:
12
Journal Article
Recenzirano
Odprti dostop
One Health is a well-recognized concept; however, it has been at the fringe of most operational health policies rather than being the central theme. Although, global experts and policy makers have ...agreed on this theory, the transition from a vision to practical application is inconspicuous. COVID-19 pandemic has caused massive damage to the world economy and continues to peril human lives everywhere. Ignorance of the principles of One Health approach in the current health care system has proved to be the Achilles heel of our health policy. Social distancing, lockdown, and hand hygiene are short-term preventive measures imposed by nations worldwide but are difficult to sustain in the long run. Thus, it is long overdue that we change our unidimensional approach regarding the control and prevention of diseases. A rational practice of the One Health strategy should be our utmost priority to control the ongoing grave situation. The purpose of this article is to bring the attention of healthcare professionals and researchers toward the One Health paradigm for the betterment of public health while combating COVID-19 and to prepare for future emergence of infectious diseases. Our assessment for this review is based on the philosophy and views shared by recent publications on the One Health approach which emphasizes an integrated, multisectoral, and holistic concept (animal health-human health-environmental factors) and promotes a transdisciplinary-integrated tactic for disease prevention and control.
The C-terminal domain of the cellular prion protein (PrPC) contains two N-linked glycosylation sites, the occupancy of which impacts disease pathology. In this study, we demonstrate that glycans at ...these sites are required to maintain an intramolecular interaction with the N-terminal domain, mediated through a previously identified copper–histidine tether, which suppresses the neurotoxic activity of PrPC. NMR and electron paramagnetic resonance spectroscopy demonstrate that the glycans refine the structure of the protein’s interdomain interaction. Using whole-cell patch-clamp electrophysiology, we further show that cultured cells expressing PrP molecules with mutated glycosylation sites display large, spontaneous inward currents, a correlate of PrP-induced neurotoxicity. Our findings establish a structural basis for the role of N-linked glycans in maintaining a nontoxic, physiological fold of PrPC.
The structure of a new cysteine framework (−CCCCCC−) “M”-superfamily conotoxin, Mo3964, shows it to have a β-sandwich structure that is stabilized by inter-sheet cross disulfide bonds. Mo3964 ...decreases outward K+ currents in rat dorsal root ganglion neurons and increases the reversal potential of the NaV1.2 channels. The structure of Mo3964 (PDB ID: 2MW7) is constructed from the disulfide connectivity pattern, i.e., 1-3, 2-5, and 4-6, that is hitherto undescribed for the “M”-superfamily conotoxins. The tertiary structural fold has not been described for any of the known conus peptides. NOE (549), dihedral angle (84), and hydrogen bond (28) restraints, obtained by measurement of h3 J NC′ scalar couplings, were used as input for structure calculation. The ensemble of structures showed a backbone root mean square deviation of 0.68 ± 0.18 Å, with 87% and 13% of the backbone dihedral (ϕ, ψ) angles lying in the most favored and additional allowed regions of the Ramachandran map. The conotoxin Mo3964 represents a new bioactive peptide fold that is stabilized by disulfide bonds and adds to the existing repertoire of scaffolds that can be used to design stable bioactive peptide molecules.
Background: COVID-19 infection is caused by corona virus SARS-COV2. the aim of the study is to assess feto-maternal outcome in severely ill covid positive pregnant females.Methods: An observational ...study was conducted at dedicated covid care center, RNT medical college Udaipur from Jan 2021 to May 2021 among pregnant females. In this study out of 236 total covid positive pregnant patients, 54 patients which could not maintain oxygen saturation, according to NIH criteria were included in our study.Results: Out of 54 pregnant women, 24 women delivered with 2 twin pregnancies. Out of this 67% underwent cesarean section and 33% were delivered by vaginal route. Postpartum hemorrhage seen in 29% of patients. Maternal death reported in 39% of patients. Out of 54 patients 38 patients were admitted in ICU. Invasive ventilation received by 26% of patients while oxygen received by non-invasive ventilation (15%), Bains (18%) rest by NRBM and venturi mask (41%). Remdesivir were given in 26 (48%) patients.Conclusions: Our study suggests there may be increased risk of adverse pregnancy outcome for mother and fetus. COVID-19 in pregnancy was associated with risks of pre-eclampsia, stillbirth, preterm birth, PPH. Similar to general population comorbidities do play a role in the outcome of disease in pregnancy. Further studies are needed for effective strategies to prevent adverse outcomes in pregnant females with COVID-19.
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