This paper is a rough precis of a recent book (GRAY, 1982). It is concerned with the question: what are the brain structures which mediate the psychology as well as the neurology of anxiety? It is clear that, once you start asking questions about the brain, you have to work with animals for reasons that are familiar to everybody. But it is very difficult to start studying emotions in animals, because it is difficult to know what emotions animals experience and whether these are the same as the human emotions. So the first thing one has to look for is a kind of crutch or bridge to get you across from the human domain on one side to the animal domain on the other. Now in the case of anxiety we are quite fortunate in that there are certain drugs which are clinically very effective in controlling anxiety in human subjects. So one can take those drugs and apply them to animals to study their behavioral effects.

The neuropsychology of anxiety

Ketamine and its enantiomer S-ketamine (esketamine) are promising candidates to produce a rapid-onset antidepressant effect in treatment-resistant depression. Ketamine causes continued blockade of the glutamate N-methyl-d-aspartate (NMDA) receptor, though this might not primarily mediate the antidepressant effect. Alternative hypotheses include selectivity for the NMDA receptor subtype containing the NMDA receptor subunit 2B (NR2B), inhibition of the phosphorylation of the eukaryotic elongation factor 2 (eEF2) kinase, increased expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrKB), and activation of the mammalian target of rapamycin (mTOR) signaling pathway, alongside other independent actions attributed to the ketamine metabolism to R-hydroxynorketamine (R-HNK). The enantiomer S-ketamine (esketamine) displays approximately fourfold greater affinity for the glutamate NMDA receptor in vitro than R-ketamine. Proof-of-concept single-dose and repeat-dose studies with intravenous ketamine show a significant antidepressant and probably antisuicidal effect in the short term, with response rates over 60% as early as 4.5 h after a single dose, with a sustained effect after 24 h, and over 40% after 7 days. This response can be further sustained over several weeks with repeated doses (two to three doses per week). Tolerability seems acceptable in the short term, with transient elevation of blood pressure and mild and transient dissociative and psychotomimetic effects. Intranasal esketamine has shown a comparable antidepressant effect, which has resulted in the US FDA granting the drug a “breakthrough therapy” designation, and theoretically it may offer an improved tolerability profile. However, major concerns remain regarding an effective protocol to maintain the clinical antidepressant effect of ketamine seen with acute administration and the safety of ketamine and esketamine in the long term, specifically related to potential neurocognitive and urologic toxicity, together with the potential induction of substance use disorders. Ketamine and esketamine are not currently approved treatments for depression, but the clinical use of ketamine is increasing in a variety of practice settings internationally.

Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review.

N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP), dizocilpine (MK-801) and ketamine have long been considered a model of schizophrenia, both in animals and humans However, ketamine has been recently approved for treatment-resistant depression, although with severe restrictions Interestingly, the dosage in both conditions is similar, and positive symptoms of schizophrenia appear before antidepressant effects emerge Here, we describe the temporal mechanisms implicated in schizophrenia-like and antidepressant-like effects of NMDA blockade in rats, and postulate that such effects may indicate that NMDA receptor antagonists induce similar mechanistic effects, and only the basal pre-drug state of the organism delimitates the overall outcome Hence, blockade of NMDA receptors in depressive-like status can lead to amelioration or remission of symptoms, whereas healthy individuals develop psychotic symptoms and schizophrenia patients show an exacerbation of these symptoms after the administration of NMDA receptor antagonists

/pdf/brain-nmda-receptors-in-schizophrenia-and-depression-2lccli7pu6.pdf

Brain NMDA Receptors in Schizophrenia and Depression.

Ketamine, a drug introduced in the 1960s as an anesthetic agent and still used for that purpose, has garnered marked interest over the past two decades as an emerging treatment for major depressive...

https://journals.sagepub.com/doi/pdf/10.1177/2045125320916657

Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers:

Fast-acting antidepressant activity of ketamine: highlights on brain serotonin, glutamate, and GABA neurotransmission in preclinical studies.

Recent evidence has suggested that the N-methyl-D-aspartate receptor antagonist ketamine shows significant therapeutic effects in major depression and bipolar disorder. This effect is especially important in treatment-resistant depression and depression with suicidal ideation. In this review we explain the mechanism of action, drug efficacy, and the side effects of ketamine; the antidepressive effects of ketamine; the individual effects of ketamine isomers, R(–) ketamine and S(+) ketamine; the effects of the combination of ketamine with electroconvulsive therapy; and the possible use of ketamine in treating depression.

https://journals.sagepub.com/doi/pdf/10.1177/2045125316631267

Ketamine enantiomers in the rapid and sustained antidepressant effects.

Osteoporosis has been recognized as one of the major diseases affecting individuals globally, including pregnant women and women who lactate An enormous amount of calcium and other minerals are required for nourishment during pregnancy and lactation During these critical stages, the homeostasis between osteoblasts and osteoclasts is perturbed A higher serum level of calcium and minerals are needed due to a decrease in Bone Mass Density (BMD) Due to the decrease in bone mass, these people have a greater chance of acquiring osteoporosis and correspondingly any osteoporosis-related fractures This review focuses on the physiology of bone and the development of osteoporosis during pregnancy and lactation

/pdf/osteoporosis-associated-with-pregnancy-4bxpcczxdt.pdf

Osteoporosis associated with Pregnancy

Biological fluid collection to identify and analyze different disease markers is a routine and normal procedure in health care settings. Body fluids are as varied as urine, blood, mucus, cerebrospinal fluid (CSF), tears, semen, etc. The volumes of the collected fluids range from micro liters (e.g., tears, CSF) to tens and hundreds of milliliters (blood, urine, etc.). In some manifestations, a disease marker (particularly protein markers) can occur in trace amounts, yet the fluids collected are in large volumes. To identify these trace markers, cumbersome methods, expensive instruments, and trained personnel are required. We developed an easy method to rapidly capture, concentrate, and identify protein markers in large volumes of test fluids. This method involves the utilization of two antibodies recognizing two different epitopes of the protein biomarker. Antibody-1 helps to capture and concentrate the biomarker and Antibody-2 adsorbed or conjugated to nanogold beads will detect the biomarker. This method was validated in capturing and detecting lipocalin type prostaglandin-D2 synthase, a marker in urine that implicates diabetic nephropathy. A one-step collection, concentration, and detection device was designed based on this method. This device can replace many of the normal body fluid collection devices such as tubes and containers. A one-step fluid collection and biomarker capture and concentration device for rapid diagnosis of diseases has tremendous advantage in terms of cost and providing timely results.

https://www.mdpi.com/2075-4418/5/2/177/pdf

A Novel Point-of-Care Biomarker Recognition Method: Validation by Detecting Marker for Diabetic Nephropathy.

The anesthesia ex utero intrapartum treatment (EXIT) procedure is a specialized surgical procedure used to deliver babies who have airway compression due to cystic adenomatoid malformation, bronchopulmonary sequestration, cervical teratomas, or other congenital conditions. EXIT is erroneously known as a routine cesarean section (CS), but is rather an extension of CS with discernible differences. The procedure creates an opening in the anesthetized abdomen of the mother and uterus. Once EXIT is complete, the remainder of the CS proceeds. EXIT is much more complex than a routine CS, as it requires coordination between the mother and a multidisciplinary team of surgical and neonatal personnel. This review highlights current anesthetic concepts during the EXIT procedure.

/pdf/ex-utero-intrapartum-treatment-exit-3ptv7m7j45.pdf

Ex Utero intrapartum treatment (EXIT)

A novel prostate cancer biomarker

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