The Role of Nucleotides in Glial Cells during Peripheral Nerve Trauma and Compressive Disorders

Studies have shown that the administration of drugs containing pyrimidine nucleotides, such as uridine triphosphate (UTP) and cytidine monophosphate (CMP), has been effective in pain-intensity reductions in patients with painful conditions as diabetic neuropathy, back pain, and cervical and trauma-compressive changes. The combination of pyrimidine nucleotides UTP and CMP is part of a peripheral neuro-regenerative process. Its pharmacological properties are stimulation of nerve cells proteins synthesis, nerve cell membranes synthesis, myelin sheaths synthesis, and neurite sprouting through P2Y receptors activation. Herein, chapter will be discussed the combination of UTP and CMP, and in some cases, the inclusion of cobalamin (B12 vitamin) that appears to have analgesic effects in neuropathic pain secondary to spine structural disorders assigned to a complex pharmacodynamic. The mechanisms involved can be both indirect (protein synthesis in nerve cells, myelin synthesis, synthesis of MBP, etc.) and direct (P2Y receptor stimulation)

A double-blind, randomized, comparative study of the use of a combination of uridine triphosphate trisodium, cytidine monophosphate disodium, and hydroxocobalamin, versus isolated treatment with hydroxocobalamin, in patients presenting with compressive neuralgias

CONTEXT: This paper reports on the results of treatment of compressive neuralgia using a combination of nucleotides (uridine triphosphate trisodium [UTP] and cytidine monophosphate disodium [CMP]) and vitamin B(12). OBJECTIVES: To assess the safety and efficacy of the combination of nucleotides (UTP and CMP) and vitamin B(12) in patients presenting with neuralgia arising from neural compression associated with degenerative orthopedic alterations and trauma, and to compare these effects with isolated administration of vitamin B(12). METHODS: A randomized, double-blind, controlled trial, consisting of a 30-day oral treatment period: Group A (n=200) receiving nucleotides + vitamin B(12,) and Group B (n=200) receiving vitamin B(12) alone. The primary study endpoint was the percentage of subjects presenting pain visual analog scale (VAS) scores ≤20 at end of study treatment period. Secondary study endpoints included the percentage of subjects presenting improvement ≥5 points on the patient functionality questionnaire (PFQ); percentage of subjects presenting pain reduction (reduction in VAS scores at study end in relation to pretreatment); and number of subjects presenting adverse events. RESULTS: The results of this study showed a more expressive improvement in efficacy evaluations among subjects treated with the combination of nucleotides + vitamin B(12), with a statistically significant superiority of the combination in pain reduction (evidenced by VAS scores). There were adverse events in both treatment groups, but these were transitory and no severe adverse event was recorded during the study period. Safety parameters were maintained throughout the study in both treatment groups. CONCLUSION: The combination of uridine, cytidine, and vitamin B(12) was safe and effective in the treatment of neuralgias arising from neural compression associated with degenerative orthopedic alterations and trauma

Craniomaxillofacial morphology alterations in children, adolescents and adults with neurofibromatosis 1 : a cone beam computed tomography analysis of a Brazilian sample

Oral manifestations are common in neurofibromatosis 1 (NF1), and include jaws and teeth alterations. Our aim was to investigate the craniomaxillofacial morphology of Brazilian children, adolescents and adults with NF1 using cone beam computed tomography. This study was conducted with 36 Brazilian individuals with NF1 with ages ranging from 4 to 75. The participants were submitted to anamnesis, extra and intraoral exam and cephalometric analysis using cone beam computed tomography. Height of the NF1 individuals was compared to the length of jaws and skull base. The results of the cephalometric measurements of the NF1 group were compared with a control group paired by age, gender and skin color. Individuals with NF1 had lower maxillary length (p<0.0001), lower mandibular length (p<0.0001), lower skull base length (p<0.0001). In children and adolescents, the mandible was more posteriorly positioned (p=0.01), when compared with the control group. There was no association between jaws and skull base length with the height of the individuals with NF1. Brazilian children, adolescents and adults with NF1 have short mandible, maxilla and skull base. Moreover, children and adolescents present mandibular retrusion

Clinical Characteristics of Alopecia Areata in Down syndrome

Aim: This study was undertaken to better understand clinical characteristics, environmental and physical events in Down syndrome (DS) and alopecia areata (AA). Material and Methods: Cross-sectional study was performed with 18 individuals with DS who were currently presenting or had presented AA. Were evaluated: gender, age, local and type of AA, presence of autoimmune disease or atopy, AA in first-degree relatives, environmental, physical and clinical intercurrences. Results: Average age was 11.6 years (y) (SD ± 5.5y) and average age of AA onset was 7.2y (2.5 to 15.2y). The duration of alopecia episodes varied; an average of 2.7y (0.1 to 18.7y) was observed. Recurrence of AA was reported in 27.7% (5/18) and the average number of recurrences was 3.6. Localized type, was seen in 83.4% of individuals, and the most frequent location was scalp (100%). Seven of the individuals presented atopy. Fourteen of the individuals had undergone environmental and/or clinical intercurrences. Conclusion: The most frequent presentation of AA in DS is the non-recurrent, localized form, on scalp, with varied period of duration. Changes in individuals’ routine, occurred in more than half of the studied group. We suggest further studies of the psychology and immunogenetics of the etiopathology of AA in DS. </span

A Renormalization Group Approach to Relativistic Cosmology

We discuss the averaging hypothesis tacitly assumed in standard cosmology. Our approach is implemented in a "3+1" formalism and invokes the coarse graining arguments, provided and supported by the real-space Renormalization Group (RG) methods. Block variables are introduced and the recursion relations written down explicitly enabling us to characterize the corresponding RG flow. To leading order, the RG flow is provided by the Ricci-Hamilton equations studied in connection with the geometry of three-manifolds. The properties of the Ricci-Hamilton flow make it possible to study a critical behaviour of cosmological models. This criticality is discussed and it is argued that it may be related to the formation of sheet-like structures in the universe. We provide an explicit expression for the renormalized Hubble constant and for the scale dependence of the matter distribution. It is shown that the Hubble constant is affected by non-trivial scale dependent shear terms, while the spatial anisotropy of the metric influences significantly the scale-dependence of the matter distribution.Comment: 57 pages, LaTeX, 15 pictures available on request from the Author

Physiological Adaptations to Life in Space: An Update

The historic flight of cosmonaut Yuri Alekeseyevich Gagarin, in 1961, established the need for research regarding the physiological adaptations of the human body when exposed to the space environment. Since then, several morpho-functional transformations – varying between normal and pathological – have been identified within the organisms of astronauts subjected to the extremely disparate environments of the cosmos, consequently, comprehension and preparation of these transformations becomes essential,considering the possibilities (1) of returning to the Moon and (2) of initiating the trip to Mars. Accordingly, the purpose of this article – conceived as a narrative literature review – is to present the main aspects of the physiological modifications within the human body due to the extraterrestrial environment, with emphasis on cardiovascular, renal, hydroelectrolytic, hematological, immunological, respiratory, neurological, psychological, sensory, gastrointestinal, endocrine, musculoskeletal, integumentary, and genetic adaptations

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins