Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial.

Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and <12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment.

METABOLIC SUPPORT FOR PATIENTS WITH MILD COGNITIVE (DODECAMENTAL) IMPAIRMENT IN THE OUTCOME OF COVID-19.

An open comparative study was conducted to assess the efficacy and safety of cytoflavin in the treatment of 50 patients who underwent SARS-CoV-2 infection, with subsequently developed mild cognitive impairment after leaving an infectious disease hospital. The survey was carried out using the Montreal Cognitive Assessment Scale (MoCA test) for the study of cognitive status, as well as the SF-36 questionnaire to determine parameters of the quality of life of patients and to assess the level of asthenia, anxiety and depression during follow-up (at the beginning of study and after 10 days of fluid therapy). Patients of the main group received intravenous infusion of cytoflavin for 10 days at a dose of 10 mL per 100 mL of 0.9% sodium chloride solution, while the comparison group received "active placebo" (100.0 mL of 0.9 sodium chloride solution) also for 10 days. During observation, the main test group patients showed significant discrepancies in the amount of complaints such as dizziness, headache, and decreased cognitive performance versus placebo group. According to the MoCA test results, patients of the main group showed higher total score on the background of improved cognitive functions: attention improved by 13.2%, p < 0.05 (subtest "repetition" of the number series in forward and reverse order and the "cotton" subtest with letter "A");regulatory skills improved by 9.8%, p < 0.05 (speaking "fluency" subtest);visual-constructive skills improved by 11.4%, p < 0.05 ("clock drawing" subtest);phrase repetition improved by 11.3%, p < 0.05, and literature associations improved by 11.3%, p < 0,05. Based on the results of the SF-36 questionnaire, the life quality was also significantly improved, by 19.5%, p < 0.05 on the average (including physical functioning and condition, pain intensity, general condition, vitality and mental health indicators). The tolerance of cytoflavin in all patients was good and there were no side effects related to the drug. Thus, the use of cytoflavin in the complex treatment of SARS-CoV-2 patients, who suffered from the infection with encephalopathy/mild cognitive impairment developed as part of the postvoid syndrome, reduces neurological deficit and helps to restore neurocognitive functions.Copyright © 2021 Eieeaeoea aaoiia

A Rare Case Of Peripartum Takotsubo Cardiomyopathy

Background: Takotsubo cardiomyopathy is characterized by left ventricular dysfunction with apical ballooning in the absence of significant coronary artery disease. Though rare in pregnancy, this transient cardiac dysfunction may affect women in antepartum, intrapartum, or postpartum period, making it difficult to discern the inciting event or differentiate from spontaneous coronary artery dissection or peripartum cardiomyopathy. Most patients respond well to medical management with spontaneous resolution of cardiac dysfunction within weeks of diagnosis. Case presentation: A 38-year-old female G3P0202 at 36 weeks of gestation with a history of preeclampsia, hypertension, hyperlipidemia, and recent COVID-19 infection presented with severe substernal chest pain. She was hypertensive on arrival with a blood pressure of 220/120 mm Hg. Electrocardiogram showed T-wave inversion in the anterior leads and troponin I level was 2.6 ng/ml. She was treated with aspirin 324 mg, IV hydralazine 20 mg, IV magnesium sulfate infusion for seizure prophylaxis and fetal neuroprotection. A transthoracic echocardiogram revealed left ventricular ejection fraction of 35-40% with apical ballooning. Urgent left heart catheterization did not show signs of epicardial coronary artery disease, prompting the diagnosis of Takotsubo cardiomyopathy. Hospital course included interdisciplinary team-based medical therapy until cesarean section 24 hours after arrival. Following delivery, she was started on guideline directed medical therapy for heart failure and discharged home. At her one month follow-up, she was still experiencing symptoms of heart failure and classified as New York Heart Association Class II. Conclusion(s): Stress-induced cardiomyopathy rarely occurs in gravid females with chest pain;however, it should be considered after ruling out acute myocardial infarction. Distinguishing Takotsubo cardiomyopathy from peripartum cardiomyopathy is important as peripartum cardiomyopathy is considered a contraindication for future pregnancies. Clinical suspicion for Takotsubo cardiomyopathy should be increased in patients with a history of superimposed preeclampsia. Whether COVID-19 infection-associated inflammatory state predisposes high risk pregnant patients to Takotsubo cardiomyopathy is unknown, but this is a possible inciting factor that should be assessed in patient work up. Management should involve an interdisciplinary team approach to ensure the safety of mother and child.Copyright © 2022

[6]-Gingerol: A narrative review of its beneficial effect on human health

Ginger rhizome, a common spice that has been traditionally used in various health aspects. The rhizome contains volatile oil and nonvolatile oil compounds, including oleoresin. Chemical constituents of ginger are numerous and vary depending on the geographic origin, harvest process, and storage conditions. [6]-Gingerol, a major bioactive constituent of ginger, has been reported to possess anti-inflammatory, antiviral, antitumor, antioxidant, and antiemetic effects. Therefore, it is a valuable food molecule with benefits for human health. This review summarized current findings on [6]-gingerol with regards to its beneficial effects on human health, encompassing the biological activities, mechanisms of action and toxicity assessment. In addition, relevant evidence in support of the application of [6]-gingerol towards the promotion health and vitality, as well as methods for extraction, identification and quantitative determination of [6]-gingerol are also provided.Copyright © 2022 The Author(s)

Is There a Rendezvous for SARS-CoV-2 and Agmatine?

The catastrophe of the ongoing COVID-19 pandemic is caused by Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). The respiratory system appears to be ground zero in the majority of the patients. However, many other organs can get infected by cytokines, chemokines and other mediators released in response to the presence of the virus. The neurotropism by the SARS-CoV-2 is established beyond doubt. In addition to non-specific symptoms, the symptoms specific to central and/or peripheral nervous system diseases as well as neuromuscular diseases have been observed in numerous clinical cases. These observations and the experiences with other coronavirus infections earlier and flu pandemics raise concerns not only about the neurological effects in active disease but also about the long-term effects generated by the infection, immune and inflammatory functions. The knowledge of biological actions of agmatine in the backdrop of physiological events instigated by invading SARS-CoV-2 and host's response, especially in neural events, focuses on the possible overlaps of biomolecular pathways at a number of instances. This is not surprising since the factors stimulated during SARS-CoV-2 infection are the disease-generating neuroinflammatory components altered by agmatine. Hence, we hypothesize the possible beneficial role of agmatine in SARS-CoV-2 infection. Based on a narrative review of the literature, agmatine can be proposed as a plausible beneficial candidate for supporting treatment of SARS-CoV-2 infection and for addressing post-infection neurological complications.Copyright © 2022 Bentham Science Publishers.

Inflammatory neuropsychiatric disorders and COVID-19 neuroinflammation.

Neuropsychiatric sequalae to coronavirus disease 2019 (COVID-19) infection are beginning to emerge, like previous Spanish influenza and severe acute respiratory syndrome episodes. Streptococcal infection in paediatric patients causing obsessive compulsive disorder (PANDAS) is another recent example of an infection-based psychiatric disorder. Inflammation associated with neuropsychiatric disorders has been previously reported but there is no standard clinical management approach established. Part of the reason is that it is unclear what factors determine the specific neuronal vulnerability and the efficacy of anti-inflammatory treatment in neuroinflammation. The emerging COVID-19 data suggested that in the acute stage, widespread neuronal damage appears to be the result of abnormal and overactive immune responses and cytokine storm is associated with poor prognosis. It is still too early to know if there are long-term-specific neuronal or brain regional damages associated with COVID-19, resulting in distinct neuropsychiatric disorders. In several major psychiatric disorders where neuroinflammation is present, patients with abnormal inflammatory markers may also experience less than favourable response or treatment resistance when standard treatment is used alone. Evidence regarding the benefits of co-administered anti-inflammatory agents such as COX-2 inhibitor is encouraging in selected patients though may not benefit others. Disease-modifying therapies are increasingly being applied to neuropsychiatric diseases characterised by abnormal or hyperreactive immune responses. Adjunct anti-inflammatory treatment may benefit selected patients and is definitely an important component of clinical management in the presence of neuroinflammation.

Heat-killed Lactobacillus murinus confers neuroprotection against dopamine neuronal loss by targeting NLRP3 inflammasome.

The intestinal flora has become very active in studies related to Parkinson's disease (PD) in recent years. The microbe-gut-brain axis is closely related to the maintenance of brain homeostasis as well as PD pathogenesis. Alterations in gut bacteria can contribute to neuroinflammation and dopamine (DA) neurodegeneration. Lactobacillus murinus, a gram-positive bacterium, is a commensal gut bacteria present in the mammalian gut and considered as a potential probiotic due to its beneficial effects, including anti-inflammatory and antibacterial actions. In this study, the effects of live L. murinus and heat-killed L. murinus on DA neuronal damage in rats and the underlying mechanisms were investigated. Data showed that heat-killed L. murinus ameliorated 6-hydroxydopamine-induced motor dysfunctions and loss of substantia nigra DA neurons, while no protection was shown in live L. murinus treatment. At the same time, heat-killed L. murinus reduced the activation of NLRP3 inflammasome in microglia and the secretion of pro-inflammatory factors, thus inhibiting the development of neuroinflammation. Furthermore, heat-killed L. murinus failed to display its original neuroprotective properties in NLRP3 inflammasome knockout mice. Together, heat-killed L. murinus conferred neuroprotection against DA neuronal loss via the inhibition of microglial NLRP3 inflammasome activation. These findings provide a promising potential for future applications of L. murinus, and also beneficial strategy for PD treatment.

COMPARATIVE EFFICACY OF VARIOUS ANTICOAGULANTS IN COVID-19 INDIAN SUBJECTS: AN OBSERVATIONAL STUDY

Background: To assess the efficacy of various anticoagulants being prescribed in the COVID 19 induced hypercoagulability, so as to know optimally effective anticoagulant. Methods: This was a Indian observational study conducted in our covid centre at vijayawada,Andhra Pradesh between june 2020 to January 2021 . Results: A total of 100 COVID 19 subjects were included. The patients were found to be matched with respect to age, gender, diet and past history of various illnesses. Gender wise more males (60 patients)are affected when compared to females(40 patients). Age group more affected are less than or equal to 50yrs . Comorbidites like Diabetes(67patients),cardiac problems(62patients), dyslipidemia(62patients) were seen. Risk factors like smoking(52patients), alcoholism(50patients) noticed. Almost all subjects are RTPCR positive. IL- 6,CRP,LDH high in most subjects. Ferritin and PT/INR are normal in more subjects. Out of 100 patients oxygen is required in 48 subjects and BIPAP/CPAP required in 26 subjects. Death occurred in 24 patients (2 with CVA,22 with myocardial infraction). Mortality rate is more in vegetarians. More patients in our study belongs to CORADS score 4 and 5. D-dimer are increased in 67subjects. IL-6 are increased in 68patients . Frequency of subjects with raised D-dimer (p = 0.049) and CRP (p = 0.002) levels were found to be benefitted on receiving nattokinase. However, no other parameters such as IL-6 (p = 0.068) ferritin (p = 0.396), ESR (p = 0.278), PT/INR (p = 0.47) LDH (p = 0.34) or CORADS staging achieved such significant association. Also need of interventions such as Oxygen (p = 0.001), BIPAP/CPAP (p < 0.0001) were low in patients on nattokinase. No significant difference was noted in follow up investigations such as PT/INR (p = 0.31) and other markers (D-dimer, IL-6, LDH, CRP) (p = 0.55). No bleeding episodes were reported in subjects on nattokinase. Significant low rate of death was found in subjects who received nattokinase (p < 0.0001) and rivaroxaban (p < 0.0001). Also, significantly higher mortality rate was observed in subjects who required to be put on oxygen (p < 0.0001) as well as BIPAP/CPAP (p < 0.0001). Conclusions: Nattokinase simultaneously effects several key favourable benefits for thrombosis, hypertension, atherosclerosis, hyperlipidaemia, platelet aggregation, and neuroprotection in patients with COVID 19 infection. (Figure Presented).

Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention.

Alpha-lipoic acid is an organic, sulfate-based compound produced by plants, humans, and animals. As a potent antioxidant and a natural dithiol compound, it performs a crucial role in mitochondrial bioenergetic reactions. A healthy human body, on the other hand, can synthesize enough α-lipoic acid to scavenge reactive oxygen species and increase endogenous antioxidants; however, the amount of α-lipoic acid inside the body decreases significantly with age, resulting in endothelial dysfunction. Molecular orbital energy and spin density analysis indicate that the sulfhydryl (-SH) group of molecules has the greatest electron donating activity, which would be responsible for the antioxidant potential and free radical scavenging activity. α-Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E. α-Lipoic acid enantiomers and its reduced form have antioxidant, cognitive, cardiovascular, detoxifying, anti-aging, dietary supplement, anti-cancer, neuroprotective, antimicrobial, and anti-inflammatory properties. α-Lipoic acid has cytotoxic and antiproliferative effects on several cancers, including polycystic ovarian syndrome. It also has usefulness in the context of female and male infertility. Although α-lipoic acid has numerous clinical applications, the majority of them stem from its antioxidant properties; however, its bioavailability in its pure form is low (approximately 30%). However, nanoformulations have shown promise in this regard. The proton affinity and electron donating activity, as a redox-active agent, would be responsible for the antioxidant potential and free radical scavenging activity of the molecule. This review discusses the most recent clinical data on α-lipoic acid in the prevention, management, and treatment of a variety of diseases, including coronavirus disease 2019. Based on current evidence, the preclinical and clinical potential of this molecule is discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-023-00370-1.

Cucurbitacin B: A review of its pharmacology, toxicity, and pharmacokinetics.

Cucurbitacin B (CuB, C32H46O8), the most abundant and active member of cucurbitacins, which are highly oxidized tetracyclic triterpenoids. Cucurbitacins are widely distributed in a variety of plants and mainly isolated from plants in the Cucurbitaceae family. CuB is mostly obtained from the pedicel of Cucumis melo L. Modern pharmacological studies have confirmed that CuB has a broad range of pharmacological activities, with significant therapeutic effects on a variety of diseases including inflammatory diseases, neurodegenerative diseases, diabetes mellitus, and cancers. In this study the PubMed, Web of Science, Science Direct, and China National Knowledge Infrastructure (CNKI) databases were searched from 1986 to 2022. After inclusion and exclusion criteria were applied, 98 out of 2484 articles were selected for a systematic review to comprehensively summarize the pharmacological activity, toxicity, and pharmacokinetic properties of CuB. The results showed that CuB exhibits potent anti-inflammatory, antioxidant, antiviral, hypoglycemic, hepatoprotective, neuroprotective, and anti-cancer activities mainly via regulating various signaling pathways, such as the Janus kinase/signal transducer and activator of transcription-3 (JAK/STAT3), nuclear factor erythroid 2-related factor-2/antioxidant responsive element (Nrf2/ARE), nuclear factor (NF)-κB, AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt, cancerous inhibitor of protein phosphatase-2A/protein phosphatase-2A (CIP2A/PP2A), Wnt, focal adhesion kinase (FAK), Notch, and Hippo-Yes-associated protein (YAP) pathways. Studies of its toxicity and pharmacokinetic properties showed that CuB has non-specific toxicity and low bioavailability. In addition, derivatives and clinical applications of CuB are discussed in this paper.

Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline.

The aim of this review is to highlight the beneficial attributes of flavonoids, a diverse family of widely-distributed polyphenolic phytochemicals that have beneficial cell and tissue protective properties. Phytochemicals are widely distributed in plants, herbs and shrubs used in traditional complimentary medical formulations for centuries. The bioactive components that convey beneficial medicinal effects in these complex herbal preparations are now being identified using network pharmacology and molecular docking procedures that identify their molecular targets. Flavonoids have anti-oxidant, anti-inflammatory, antiviral, antibacterial and anti-cancer properties that have inspired the development of potent multifunctional derivatised flavonoids of improved efficacy. The antiviral properties of flavonoids and the emergence of the severe acute respiratory syndrome (SARS-CoV-2) pandemic has resulted in a resurgence of interest in phytochemicals in the search for efficacious compounds that can prevent viral infection or replication, with many promising plant compounds identified. Promising semi-synthetic flavonoid derivatives have also been developed that inhibit multiple pathological neurodegenerative processes; these offer considerable promise in the treatment of diseases of cognitive decline. Clinical trials are currently being undertaken to evaluate the efficacy of dietary supplements rich in flavonoids for the treatment of virally-mediated diseases. Such trials are expected to identify flavonoids with cell and tissue protective properties that can be harnessed in biomedical applications that may serve as supportive adjunctive procedures to conventional anti-viral drug therapies against diseases such as COVID-19.

Difficulties and prospects of rational therapy of ischemic strokes

Despite significant progress in medical technology, many topical issues in neurology remain unresolved;among the latter, acute cerebrovascular accidents (strokes) continue to be one of the most important medical and social problems of the modern world, since their rates of morbidity, mortality and disability are steadily growing. The increase in the incidence of strokes over the past 30 years by 70% reflects the imperfection of modern medical strategies for the primary prevention of stroke and measures for their implementation among the population, which dictates the need to revise the prevailing ideas about the etiology, patho-genetic mechanisms and therapeutic approaches to managing patients with cerebrovascular pathology. The article presents a classification of strokes, a critical analysis of vascular risk factors (in particular, the emergence of new ones, such as acute coronavirus infection COVID-19), fundamental elements of the ischemic cascade, pathomorphological and pathophysiological consequences of ischemic damage to the central nervous system (necrosis and apoptosis of neurons, diaschisis in the penumbra zone), current theoretical (targets of drug exposure) and practical (therapeutic window) aspects of therapy and prevention of acute cerebrovascular accidents are outlined. The place and importance of the use of neuroprotective drugs in the combined therapy of patients with acute and chronic cerebrovascular pathology has been demonstrated. Particular attention is focused on neurometabolic drugs with a multimodal mechanism of action, which not only protect the neuronal cytoskeleton, but also increase the tolerance of brain tissue to hypoxia. © 2022, Remedium Group Ltd. All rights reserved.

Pexidartinib (PLX3397) through restoring hippocampal synaptic plasticity ameliorates social isolation-induced mood disorders.

Social behavior is essential for the well-being and survival of individuals. However, social isolation is a serious public health issue, especially during the COVID-19 pandemic, affecting a significant number of people worldwide, and can lead to serious psychological crises. Microglia, innate immune cells in the brain, are strongly implicated in the development of psychiatry. Although many microglial inhibitors have been used to treat depression, there is no literature report on pexidartinib (PLX3397) and social isolation. Herein, we adopted PLX3397 to investigate the role of microglia in the modulation of social isolation. Our results found that social isolation during adolescence caused depressive-like, but not anxiety-like behavior in mice in adulthood, with enhanced expression of the microglial marker Iba1 in the hippocampus. In addition, treatment with PLX3397 reduced the expression of the microglial marker Iba1, decreased the mRNA expression of IL-1ß, increased the mRNA expression of Arg1, elevated the protein levels of DCX and GluR1 and restored the dendritic spine branches and density, ultimately mitigating depressive-like behavior in mice. These findings suggest that inhibition of microglia in the hippocampus could ameliorate mood disorders in mice, providing a new perspective for the treatment of psychiatric disorders such as depression.

A review: The phytochemistry, pharmacology, and pharmacokinetics of Curcumae Longae Rhizoma (Turmeric)

Curcumae Longae Rhizoma (CLR) is the rhizome of Curcuma longa L. Pharmacological studies show that CLR can be used to treat cervical cancer, lung cancer, lupus nephritis, and other conditions. In this paper, we review botany, traditional application, phytochemistry, pharmacological activity, and pharmacokinetics of CLR. The literature from 1981 to date was entirely collected from online databases, such as Web of Science, Google Scholar, China Academic Journals full-text database (CNKI), Wiley, Springer, PubMed, and ScienceDirect. The data were also obtained from ancient books, theses and dissertations, and Flora Reipublicae Popularis Sinicae. There are a total of 275 compounds that have been isolated from CLR, including phenolic compounds, volatile oils, and others. The therapeutic effect of turmeric has been expanded from breaking blood and activating qi in the traditional sense to antitumor, anti-inflammatory, antioxidation, neuroprotection, antibacterial, hypolipidemic effects, and other benefits. However, the active ingredients and mechanisms of action related to relieving disease remain ill defined, which requires more in-depth research and verification at a clinical level.

An insight into the neuroprotective effects and molecular targets of pomegranate (Punica granatum) against Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that still has no permanent cure. The drugs prescribed in the present days are only for symptomatic relief for the patients. Many studies correlating the reduction in the incidence of AD with the diet consumed have been published. These studies showed that a diet rich in polyphenols is associated with a decrease in the incidence of AD. The present review is focused on the ability of pomegranate and its bioactive components to ameliorate the progression of AD and their ability to exert a neuroprotective effect. Various studies showing the ability of pomegranate in inhibiting enzymes, reducing reactive oxygen species, inhibition of microglial activation, inhibition of tau protein hyperphosphorylation, maintenance of synaptic plasticity, anti-inflammatory activity and its ability to inhibit Beta secretase-1 (BACE-1) has been reviewed in this article. In spite of the lack of studies on humans, there are compelling evidence indicating that pomegranate can reduce various risk factors involved in the causation of AD and thus can be used as a persistent nutraceutical to slow ageing and for providing neuroprotection for the treatment of AD.Abbreviations: ACh, Acetylcholine; AChE, Acetylcholinesterase; AD, Alzheimer's disease; AGEs, Advanced Glycation End products; APP, Amyloid precursor protein; Aß, Amyloid-beta; BACE, Beta secretase or ß-site amyloid precursor protein cleaving enzyme; BBB, Blood brain barrier; BDNF, Brain derived neurotrophic factor; BuChE, Butyrylcholinesterase; CAM, Chick Chorioallantoic Membrane; COVID 19, Corona virus disease 19; COX, Cyclooxygenase; DPPH, 2,2 diphenyl picryl hydrazyl; ER, Endoplasmic Reticulum; FAO, Food and Agriculture organization; FDA, Food and drug administration; GFAP, Glial-fibrillar acidic protein; GPx, Glutathione peroxidase; GSH, Glutathione; GST, Glutathione S transferase; HFD, High-fat diet; IL-6, Interleukin-6; LDH, Lactate dehydrogenase; LO, Lipooxygenase; LPS, Lipopolysaccharide; MAO, Mono amine oxidase; MDA, Malondialdehyde; MedDi, Mediterranean diet; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; mTOR, Mammalian Target of Rapamycin; NAD, Nicotinamide adenine dinucleotide; NFAT, Nuclear factor of activated T-cells; NO, Nitric oxide; NQO1, Quinone oxidoreductase 1; Nrf2, Nuclear factor erythroid 2-related factor 2; oAß, Oligomeric amyloid-beta; pCREB, Cyclic AMP-Response Element Binding Protein; PGE2, Prostaglandin E2; RON, Reactive nitrogen species; ROS, Reactive oxygen species; SOD, Superoxide dismutase; STZ, Streptozotocin; TNF-α, Tumor necrosis factor α; UNESCO, The United Nations Educational, Scientific and Cultural Organization; WHO, World Health Organization.

Neonatal RSV positive bronchiolitis with fulminant viral septic shock

AimsMain purpose of presenting this clinical case is that RSV BRONCHIOLITIS can present with lobar pneumonia,Fulminant viral septic shock with DIC,pulmonory haemorrhage and asystole. Viral VS Bacterial sepsis- clinically difficult to differentiate.Methods1 month old girl,unwell for 2 days with cough,decrease oral intake, seen by GP in the morning and diagnosed as BRONCHIOLITIS,same day evening presented to the hospital with apnoea in the car arrived at PAU within 3 mins of apnoea.O/E-no HR or breathing,bleeding from nose and mouth,pale looking,mottled, CRT 5 sec.CPR started and connected to monitor showed asystole.Immediate cardiac arrest call was activated.Intubated, cannula inserted, 2 doses of adrenaline given IV,Bolus of normal saline 10mls/kg thrice,partial septic screening done and covered with triple antibiotics amoxycillin,gentamycin and cefotaxime.After 10 mins of resuscitation baby responded. Given vitamin K and transfused with O negative blood and FFP.Blood gas showed mixed metabolic and respiratory acidosis and hence connected to ventilator started on morphine,maintenance fluids,ionotropes,morphine infusion and transferred to tertiary centre. In tertiary centre admitted for 11 days,extubated to CPAP on day 5, weaned to high flow on day 6, RA on day 9. Ionotropes for 1 day,acylovir, vitamin k for 9 and 6 days respectively.Neuroprotective measures followed.ResultsNPA for RSV positive, covid 19 PCR negative, blood c/s,CSF c/s and CSF PCR for bacteria and viruses negative, X ray chest consolidation upper lobes bilateral,CT Angiogram subsegmental consolidation and possible intraparenchymal haemorrhage. Initial Echo pulmonory hypertension and repeat Echo normal.MRI Brain -hypersensitivity in posterior putamina. Deranged coagulation profile.APTT more than 180, PT 16.2, INR 1.4ConclusionRSV positive bronchiolitis with all complications can mimic bacterial sepsis and its clinically difficult to differentiate between viral and bacterial septic shock.As this baby’s blood C/S was negative only positive thing was RSV in NPA, We have to consider this case as RSV BRONCHIOLITIS with fulminant septic shock with pneumonia, DIC, Pulmonory Haemorrhage leading to Asystole.Management of bacterial and viral Septic shock is pretty much the same except in certain cases we may have to use antivirals drugs when indicated.

Why antidiabetic drugs are potentially neuroprotective during the Sars-CoV-2 pandemic: The focus on astroglial UPR and calcium-binding proteins.

We are living in a terrifying pandemic caused by Sars-CoV-2, in which patients with diabetes mellitus have, from the beginning, been identified as having a high risk of hospitalization and mortality. This viral disease is not limited to the respiratory system, but also affects, among other organs, the central nervous system. Furthermore, we already know that individuals with diabetes mellitus exhibit signs of astrocyte dysfunction and are more likely to develop cognitive deficits and even dementia. It is now being realized that COVID-19 incurs long-term effects and that those infected can develop several neurological and psychiatric manifestations. As this virus seriously compromises cell metabolism by triggering several mechanisms leading to the unfolded protein response (UPR), which involves endoplasmic reticulum Ca2+ depletion, we review here the basis involved in this response that are intimately associated with the development of neurodegenerative diseases. The discussion aims to highlight two aspects-the role of calcium-binding proteins and the role of astrocytes, glial cells that integrate energy metabolism with neurotransmission and with neuroinflammation. Among the proteins discussed are calpain, calcineurin, and sorcin. These proteins are emphasized as markers of the UPR and are potential therapeutic targets. Finally, we discuss the role of drugs widely prescribed to patients with diabetes mellitus, such as statins, metformin, and calcium channel blockers. The review assesses potential neuroprotection mechanisms, focusing on the UPR and the restoration of reticular Ca2+ homeostasis, based on both clinical and experimental data.

Treatments in Ischemic Stroke: Current and Future.

BACKGROUND AND AIM: Despite progress made over the last 30 years, stroke is still a leading cause of disability and mortality; likewise, its burden is expected to increase over the next decades, due to population growth and aging. The development of drugs with better safety-efficacy profiles as well as strategies able to improve ischemic stroke management from the pre-hospital setting is needed. SUMMARY: The pathophysiology of ischemic stroke involves multiple pathways resulting in cerebral artery obstruction and brain tissue ischemia. To date, the only approved drug for acute ischemic stroke is intravenous thrombolytic alteplase. Intravenous thrombolysis (IVT) can be administered alone or in combination with endovascular treatment (EVT) with mechanical thrombectomy, in case of large vessel occlusion and generally within 6 h from symptoms onset. The risk of potential bleeding complications, especially symptomatic intracerebral hemorrhage, is one of the reasons for the reluctance to administer IVT. Tenecteplase is a promising alternative fibrinolytic agent, having a better safety profile than alteplase. Moreover, recent evidences have allowed an extension of the IVT ± EVT time window for patients with unknown onset time and for those with a known onset time thanks to the new "tissue-window" approach guided by advanced neuroimaging techniques, which also helps in collateral circulation estimation. Regarding primary-secondary prevention, researchers are focused on improving the efficacy of antithrombotic drugs with a "hemostasis-sparing" approach. Neuroprotective agents are also under development, particularly stem cells. The COVID-19 pandemic has critically stressed global healthcare systems, with collateral damage resulting in access delivery of only emergency care, such as ischemic stroke. Regarding telemedicine, it has had a minor role in acute stroke management, and with the onset of COVID-19, this role will most likely be adopted to increase access and delivery in stroke assessment, but also in the follow-up.

Biomedical and Potential Therapeutic Aspects of Lithium Carbonate Use

Background: lithium carbonate salts are used in psychiatry for agitated states reduction and, above all, to prevent recurring manic and depressive episodes, as well as for the treatment of aggressive behavior. The pharmacological characteristics of lithium carbonate have not been fully studied. Recently, there has been an increasing interest in the wider use of Lithium carbonate, in particular, in the treatment of neurodegenerative diseases, and even in viral infections. Objective: to present an overview of the earliest and late foreign studies covering the biomedical and potential therapeutic aspects of lithium off-label use as follows for Alzheimer’s disease and viral infections. Material and methods: the keywords “lithium carbonate, neuroprotection, toxicity, Alzheimer’s disease, coronavirus infection” were used to search for scientific publications in the databases MEDLINE, PubMed, Scopus for the period 1970–2021. Conclusions: lithium carbonate can have significant effects on pathogenesis of Alzheimer’s disease, which may be a good prospect in the treatment of this currently incurable disorder. It is also important to note the antiviral properties of lithium carbonate. Lithium carbonate is able to mitigate the immune-in ammatory activation observed during episodes of bipolar disorder, including the normalization of cytokine levels. It is also important to note the antiviral capabilities of lithium carbonate. The most interesting is the direct impact of lithium carbonate on some members of the coronavirus family, which is especially important in connection with the real problems a global public health crisis associated with the SARS-CoV-2 virus. © 2022. Psychiatry (Moscow). All Rights Reserved.