Morphine-Mediated Cytoprotection against Hemin in SK-N-SH and A172 Cells

The toxicity of free heme has been documented in several disease types. For example, in hemolytic anemias such as sickle cell disease and thalassemia, release of heme from hemoglobin following lysis of red bloodcells is known to cause cell death. In a critical care situation such as hemorrhagic injury, neuronal cell death is caused by the lysis of red blood cells, which release hemoglobin and its breakdown product hemin. Physiological levels of free heme in the blood are maintained at low levels (0.1 -1 μM) by the high binding affinity of proteins such as serum albumin, hemopexin and haptoglobin. 

When internalized, free heme is catabolized by heme oxygenases (HO1 and HO2 isoforms) and therefore the amount of cellular damage free hemeproduces is limited by the stress-responsive HO1 isoform. In addition to HO1 and HO2 isoform regulated cellular damage, the oxidative state of iron (from Fe2+ to Fe3+ via the Fenton reaction) within heme can produce harmful superoxide free radicals in the brain that can lead to oxidative stress, initiation of lipid peroxidation and neuronal death.

Use of Randomized Submaximal Glutamate Stimulus to Interpret Glial Effects on Neuronal Calcium Dynamics

The neuronal synapse is a dynamic functional unit which is composed of neurons and support glial cells, which provide the important function of glutamate re-uptake. We have previously described calcium dynamicsin neuronal cultures treated with toxic and non-toxic concentrations ofglutamate using single stimuli of micromolar glutamate . Here we investigated whether a pattern of multiple, submaximal glutamate stimulations at nanomolar concentrations of glutamate affected calcium dynamics in neuronal cultures with and without high glial content, and whether the order of addition of nanomolar glutamate affected calcium dynamics. Calcium is a key signaling ion involved in memory and learning with ionotropic glutamate receptors such as the N-methyl-D-aspartate receptors (NMDAR) on the neuronal membrane. 

 NMDARs are a major subtype of ionotropic receptors responsible for binding glutamate, the most abundant excitatory neurotransmitter (excitatory stimulus) in the human brain. Activation of NMDARs opens the ion channel at theplasma membrane to allow calcium influx into the cell cytosol. Calcium in its ionic form is very dynamic, especially in excitable cells such as muscle and brain cells, moving from the high concentration exterior of the cell to the much lower concentrations inside the cell where calcium is used as a second messenger.

The Challenge of Overcoming Schizophrenia and a True Vision for the Future

The agony of a schizophrenic patient is unimaginable. I am a patient of schizophrenia from 1993. Advancements in science and technology, the progress of medical science and the unending quest in medical science for recovery has urged the scientific domain to ponder towards giant strides in medical history. The author withlucid details uncovers the intricate details of the cause and effects of thedangerous ailment of schizophrenia. The path to recovery for a sufferer is immense and scientifically unjustified. Yet the world of challenges, the immense grit and determination has made my life more easier. The medical science of schizophrenia is inspiring to the doctors and scientists and has opened a world of innovation and scientific research pursuit. The challenge, the enigma and the progress of the illness has opened a new world of scientific vision and scientific fortitude. 

Vision, aim and mission of the study are wide, versatile and many. The author, with strong inner vision, relates the every step of his life and his ailment. The agonizing days are delineated in details. It was in the month of June, 1993, I wasconfused, derailed and in a wayward direction. My life changed towards a devastating direction. I am a postgraduate in Chemical Engineering from Jadavpur University, Kolkata, India. I graduated in December, 1992 and soon took admission to the postgraduate course in the same university in 1992. It was one and a project supervised by a Faculty from my Department of Chemical Engineering.

Diurnal Variations of Endogenous Steroids in the Follicular Phase of the Menstrual Cycle

Many studies have been conducted assessing biological changes in patients with both somatic and psychiatric conditions. Most studies of posttraumatic stress disorder (PTSD) have focused on the primary stress pathway: the hypothalamus-pituitary-adrenal axis (HPA), which is activated during acute stress. The hypothalamus secretes corticotropin-releasing factor (CRF) whichstimulates the pituitary to release adrenocorticotropic hormone (ACTH), resulting in the production of glucocorticoids and other steroids in the adrenal cortex. It is known that the secretion of cortisol is associated with the natural circadian rhythm, and the assessment of cortisol concentrations should be adjusted for the diurnal variation, with peak values in the morning just after awakening. As cortisol is one of the end products of the glucocorticoid biosynthesis pathway, it can be assumed that the biosynthesis of glucocorticoids upstream and other steroids also are affected by diurnal variations.

Dehydroepiandosterone (DHEA) and its sulfate (DHEAS) are synthesized from cholesterol, via pregnenolone (sulfate) and 17-hydroxypregnenolone, almost exclusively by theadrenals, only ± 10% of plasma DHEA is derived from the gonads. DHEAS is quantitatively the major steroid hormone secreted by the adrenals, and its plasma concentration in young adults is 10 to 20 times the cortisol concentration.

Role of Neurotransmitter and Behavioral Changes in Mice due to Light- Dark Stress

The behavior and physiology of most of the animals existing on the earth are reliant on the 24-hour cyclic clock called light-dark cycle (LD). Disturbance of LD cycle affects the normal functions of living organisms by disturbing their circadian rhythm. The inbuilt endogenous oscillators command the circadian rhythm such as blood pressure, heart rate, sleep-wake cycle, hormonal secretion and metabolism. The central circadian clock of mammals is maintained by the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. Mammals have the most complex and well-formulated circadian rhythm centered with light-dark cycle and sleep. Mice, the nocturnal animal does most of its active work during the dark phase, which is in contrary to the diurnal animals, which does majority of the activity in light phase. Sleep is regulated by homeostatic interaction of circadian processes, which controls the duration and optimal time for sleep. Similarly the behavioral rhythms of rats were found deregulated with arrhythmic behavior when their circadian rhythms were disturbed by short light-dark and continuous light-dark exposures. From our earlier study it has been shown that disturbances to LD cycle by exposing to continuous light or dark conditions causes adverse effect on zebra fish by deregulating large number of genes and proteins .

It is well understood that neurotransmitter plays prominent role in maintenance of circadian cycle by exhibiting its function in SCN. Fluctuations in the level of neurotransmitter in rat were observed when they were exposed to disturbed light-dark cycles. In this study we aimed to understand the effective role of disturbance of LD cycle in mice by exposing the animals to continuous light and dark conditions.