Nitrogen metabolism of the isolated tissues of the rat

Little study has been devoted to the anabolic aspects of nitrogen metabolism in animals. The reason, of course, has been the difficulty of obtaining experimental conditions in which these can be observed, measured, and analyzed. The experiments of Krebs and Henseleit (1) on the formation of urea from ammonia with Warburg’s method of surviving slices of liver suggested that this method might be useful in a direct attack on a number of problems of nitrogen anabolism in animals; i.e., it might be possible to observe reactions in which there is a gain in free energy. It appears that for these reactions the intact cell structure is necessary

The oxidation of ascorbic acid and its reduction in vitro and in vivo

The outstanding chemical property of ascorbic acid (vitamin C) is that it is a reducing agent. The suggestion is obvious that its physiological function may be associated with this property, and, if it is oxidized reversibly, with its behavior in an oxidation-reduction system. It is desirable therefore to know the oxidation-reduction potential of ascorbic acid

Transient and Persistent Pain Induced Connectivity Alterations in Pediatric Complex Regional Pain Syndrome

Evaluation of pain-induced changes in functional connectivity was performed in pediatric complex regional pain syndrome (CRPS) patients. High field functional magnetic resonance imaging was done in the symptomatic painful state and at follow up in the asymptomatic pain free/recovered state. Two types of connectivity alterations were defined: (1) Transient increases in functional connectivity that identified regions with increased cold-induced functional connectivity in the affected limb vs. unaffected limb in the CRPS state, but with normalized connectivity patterns in the recovered state; and (2) Persistent increases in functional connectivity that identified regions with increased cold-induced functional connectivity in the affected limb as compared to the unaffected limb that persisted also in the recovered state (recovered affected limb versus recovered unaffected limb). The data support the notion that even after symptomatic recovery, alterations in brain systems persist, particularly in amygdala and basal ganglia systems. Connectivity analysis may provide a measure of temporal normalization of different circuits/regions when evaluating therapeutic interventions for this condition. The results add emphasis to the importance of early recognition and management in improving outcome of pediatric CRPS

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

When light hurts: Comparative Morphometry of Human Brainstem in Traumatic Photalgia

Traumatic brain injury is an increasingly common affliction, although many of its serious repercussions are still underappreciated. A frequent consequence is the development of light-induced pain, or ‘photalgia’, which can often lead to prolonged debilitation. The mechanism underlying the sensitivity to light, however, remains unresolved. Since tissue oedema (swelling) is a common feature of traumatic brain injury, we propose that the brainstem oedema, in particular, might sensitize the brainstem trigeminal complex to signals from ocular mechanisms activated in bright light. To assess this hypothesis, we ran high-resolution Magnetic Resonance Imaging of the brainstems of concussion groups with mild and severe photalgia, without photalgia, and healthy controls. The 3D configuration of the brainstem was determined by Tensor-Based Morphometry (TBM) for each participant. The TBM revealed significant deviations in the brainstem morphology of all concussion groups, with a characteristic signature for each group. In particular, concussion without photalgia showed bilateral expansion at the pontine/medulla junction, whereas concussion with photalgia showed mid-pontine shrinkage, consistent with degeneration of nuclei of the trigeminal complex. These results support the hypothesis that brainstem shrinkage/degeneration represents a morphological substrate of the photalgic sensitization of the trigeminal pathway

Central modulation in cluster headache patients treated with occipital nerve stimulation: an FDG-PET study

Peer reviewe

Sensory capacity of reinnervated skin after redirection of amputated upper limb nerves to the chest

Targeted reinnervation is a new neural-machine interface that has been developed to help improve the function of new-generation prosthetic limbs. Targeted reinnervation is a surgical procedure that takes the nerves that once innervated a severed limb and redirects them to proximal muscle and skin sites. The sensory afferents of the redirected nerves reinnervate the skin overlying the transfer site. This creates a sensory expression of the missing limb in the amputee's reinnervated skin. When these individuals are touched on this reinnervated skin they feel as though they are being touched on their missing limb. Targeted reinnervation takes nerves that once served the hand, a skin region of high functional importance, and redirects them to less functionally relevant skin areas adjacent to the amputation site. In an effort to better understand the sensory capacity of the reinnervated target skin following this procedure, we examined grating orientation thresholds and point localization thresholds on two amputees who had undergone the targeted reinnervation surgery. Grating orientation thresholds and point localization thresholds were also measured on the contralateral normal skin of the targeted reinnervation amputees and on analogous sites in able-bodied controls. Grating orientation thresholds for the reinnervated skin of the targeted reinnervation amputees were found to be similar to normal ranges for both the amputees’ contralateral skin and also for the control population. Point localization thresholds for these amputees were found to be lower for their reinnervated skin than for their contralateral skin. Reinnervated point localization thresholds values were also lower in comparison to homologous chest sites on the control population. Mechanisms appear to be in place to maximize re-established touch input in targeted reinnervation amputees. It seems that sound sensory function is provided to the denervated skin of the residual limb when connected to afferent pathways once serving highly functionally relevant regions of the brain. This suggests that tactile interface devices could be used to give a physiologically appropriate sense of touch to a prosthetic limb, which would likely help with better functional utilization of the prosthetic device and possibly help to more effectively integrate the device with the user's self-image

Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula, anterior cingulate, and amygdala

Functional neuroimaging investigations of pain have discovered a reliable pattern of activation within limbic regions of a putative "pain matrix" that has been theorized to reflect the affective dimension of pain. To test this theory, we evaluated the experience of pain in a rare neurological patient with extensive bilateral lesions encompassing core limbic structures of the pain matrix, including the insula, anterior cingulate, and amygdala. Despite widespread damage to these regions, the patient's expression and experience of pain was intact, and at times excessive in nature. This finding was consistent across multiple pain measures including self-report, facial expression, vocalization, withdrawal reaction, and autonomic response. These results challenge the notion of a "pain matrix" and provide direct evidence that the insula, anterior cingulate, and amygdala are not necessary for feeling the suffering inherent to pain. The patient's heightened degree of pain affect further suggests that these regions may be more important for the regulation of pain rather than providing the decisive substrate for pain's conscious experience