Objective
To assess the relationship between the phenotype of the “visual snow” syndrome, comorbid migraine, and typical migraine aura on a clinical basis and using functional brain imaging.
...Background
Patients with “visual snow” suffer from continuous TV‐static‐like tiny flickering dots in the entire visual field. Most patients describe a syndrome with additional visual symptoms of the following categories: palinopsia (“afterimages” and “trailing”), entopic phenomena arising from the optic apparatus itself (floaters, blue field entoptic phenomenon, photopsia, self‐light of the eye), photophobia, nyctalopia (impaired night vision), as well as the non‐visual symptom tinnitus. The high prevalence of migraine and typical migraine aura in this population has led to the assumption that “visual snow” is caused by persistent migraine aura. Due to the lack of objective measures, alternative diagnoses are malingering or a psychogenic disorder.
Methods
(1) The prevalence of additional visual symptoms, tinnitus, and comorbid migraine as well as typical migraine aura was assessed in a prospective semi‐structured telephone interview of patients with “visual snow.” Correlations were calculated using standard statistics with P < .05 being considered statistically significant. (2) Areas with increased brain metabolism in a group of “visual snow” patients in comparison to healthy controls were identified using 18F‐2‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography and statistical parametric mapping (SPM8 with whole brain analysis; statistical significance was defined by P < .001 uncorrected for multiple comparisons).
Results
(1) Of 120 patients with “visual snow,” 70 patients also had migraine and 37 had typical migraine aura. Having comorbid migraine was associated with an increased likelihood of having palinopsia (odds ratio OR 2.8; P = .04 for “afterimages” and OR 2.6; P = .01 for “trailing”), spontaneous photopsia (OR 2.9; P = .004), photophobia (OR 3.2; P = .005), nyctalopia (OR 2.7; P = .01), and tinnitus (OR 2.9; P = .006). Typical migraine aura was associated with an increased likelihood of spontaneous photopsia (OR 2.4; P = .04). (2) After adjusting for typical migraine aura, comparison of 17 “visual snow” patients with 17 age and gender matched controls showed brain hypermetabolism in the right lingual gyrus (Montreal Neurological Institute coordinates 16‐78‐5; kE = 101; ZE = 3.41; P < .001) and the left cerebellar anterior lobe adjacent to the left lingual gyrus (Montreal Neurological Institute coordinates ‐12‐62‐9; kE = 152; ZE = 3.28; P = .001).
Conclusions
—Comorbid migraine aggravates the clinical phenotype of the “visual snow” syndrome by worsening some of the additional visual symptoms and tinnitus. This might bias studies on “visual snow” by migraineurs offering study participation more likely than non‐migraineurs due to a more severe clinical presentation. The independence of entoptic phenomena from comorbid migraine indicates “visual snow” is the main determinant. The hypermetabolic lingual gyrus confirms a brain dysfunction in patients with “visual snow.” The metabolic pattern differs from interictal migraine with some similarities to migrainous photophobia. The findings support the view that “visual snow,” migraine, and typical migraine aura are distinct syndromes with shared pathophysiological mechanisms that need to be addressed in order to develop rational treatment strategies for this disabling condition.
Mechanisms discovered to drive increased glucose metabolism in cancer cells are found to be similar to those in viral‐infected cells. In this mini review, we summarize the major pathways by which the ...sugar analog, 2‐Deoxy‐d‐glucose, has been shown to exploit increased glucose metabolism in cancer and how this information applies to viral‐infected cells. Moreover, we highlight the relevance of these findings to the emergency approval of 2‐Deoxy‐d‐glucose in India to be used against SARS‐CoV‐2, the virus responsible for COVID‐19.
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•Quantitative analytical method of nine monosaccharides.•Change of monosaccharides during processing of KBT.•Theaflavins inhibit the caramelization of D-glucose.•Theaflavins-glucose ...adducts were identified.
Monosaccharides of Keemun black tea were quantitatively determined by high performance liquid chromatography coupled with 3-methyl-1-phenyl-2-pyrazolin-5-one (PMP) pre-column derivatization. The methodology of developed analytical method was established with good linearity, recovery, repeatability and precision. The quantitative results showed that D-mannose, D-glucuronic acid, D-glucose, D-galactose and L-arabinose were detected in Keemun black tea samples. D-glucose was the predominant monosaccharide in black tea, and its concentration was continuously increased from fresh tea leaves to fermentation, but after drying its concentration was significantly decreased. Meanwhile, theaflavins’ concentrations were obviously decreased after drying. When theaflavins were heated with D-glucose, the loss of theaflavins was increased. Correspondingly, theaflavins also prevented the caramelization of D-glucose and restored the loss of D-glucose during heating. Through the liquid chromatography/electrospray tandem mass spectrometry some theaflavins glucose adducts were identified.
The haloarchaeon Haloferax volcanii degrades D‐glucose via the semiphosphorylative Entner‐Doudoroff pathway and D‐fructose via a modified Embden‐Meyerhof pathway. Here, we report the identification ...of GfcR, a novel type of transcriptional regulator that functions as an activator of both D‐glucose and D‐fructose catabolism. We find that in the presence of D‐glucose, GfcR activates gluconate dehydratase, glyceraldehyde‐3‐phosphate dehydrogenase and pyruvate kinase and also acts as activator of the phosphotransferase system and of fructose‐1,6‐bisphosphate aldolase, which are involved in uptake and degradation of D‐fructose. In addition, glyceraldehyde‐3‐phosphate dehydrogenase and pyruvate kinase are activated by GfcR in the presence of D‐fructose and also during growth on D‐galactose and glycerol. Electrophoretic mobility shift assays indicate that GfcR binds directly to promoters of regulated genes. Specific intermediates of the degradation pathways of the three hexoses and of glycerol were identified as inducer molecules of GfcR. GfcR is composed of a phosphoribosyltransferase (PRT) domain with an N‐terminal helix‐turn‐helix motif and thus shows homology to PurR of Gram‐positive bacteria that is involved in the transcriptional regulation of nucleotide biosynthesis. We propose that GfcR of H. volcanii evolved from a PRT‐like enzyme to attain a function as a transcriptional regulator of central sugar catabolic pathways in archaea.
A novel transcriptional regulator, GfcR, has been identified that activates the degradation pathways of glucose, fructose, galactose and glycerol in the archaeon Haloferax volcanii. GfcR comprises a phosphoribosyltransferase domain with an N‐terminal helix‐turn‐helix DNA‐binding motif. Activation proceeds via a feedforward mechanism, where specific intermediates of the degradation pathways bind to GfcR and induce transcription of enzymes within those pathways. These data expand our knowledge of transcriptional regulation of central metabolic pathways in archaea.
Dopaminergic denervation in patients with Parkinson's disease is associated with changes in brain metabolism. Cerebral in-vivo mapping of glucose metabolism has been studied in severe stable ...parkinsonian monkeys, but data on brain metabolic changes in early stages of dopaminergic depletion of this model is lacking. Here, we report cerebral metabolic changes associated with progressive nigrostriatal lesion in the pre-symptomatic and symptomatic stages of the progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson's Disease. Monkeys (Macaca fascicularis) received MPTP injections biweekly to induce progressive grades of dopamine depletion. Monkeys were sorted according to motor scale assessments in control, asymptomatic, recovered, mild, and severe parkinsonian groups. Dopaminergic depletion in the striatum and cerebral metabolic patterns across groups were studied in vivo by positron emission tomography (PET) using monoaminergic (11C-dihydrotetrabenazine; 11C-DTBZ) and metabolic (2-18F-fluoro-2-deoxy-d-glucose; 18F-FDG) radiotracers. 11C-DTBZ-PET analysis showed progressive decrease of binding potential values in the striatum of monkeys throughout MPTP administration and the development of parkinsonian signs. 18F-FDG analysis in asymptomatic and recovered animals showed significant hypometabolism in temporal and parietal areas of the cerebral cortex in association with moderate dopaminergic nigrostriatal depletion. Cortical hypometabolism extended to involve a larger area in mild parkinsonian monkeys, which also exhibited hypermetabolism in the globus pallidum pars interna and cerebellum. In severe parkinsonian monkeys, cortical hypometabolism extended further to lateral-frontal cortices and hypermetabolism also ensued in the thalamus and cerebellum. Unbiased histological quantification of neurons in Brodmann's area 7 in the parietal cortex did not reveal neuron loss in parkinsonian monkeys versus controls. Early dopaminergic nigrostriatal depletion is associated with cortical, mainly temporo-parietal hypometabolism unrelated to neuron loss. These findings, together with recent evidence from Parkinson's Disease patients, suggest that early cortical hypometabolism may be associated and driven by subcortical changes that need to be evaluated appropriately. Altogether, these findings could be relevant when potential disease modifying therapies become available.
•Major features of early PD metabolism are recapped in the parkinsonian monkey model.•Early dopamine loss is related with cortical, mainly temporo-parietal hypometabolism.•Cortical hypometabolism is not related to neuronal loss in the cortex.
Similar to 18F-FDG, 99mTcTc-1-thio-D-glucose (99mTcTc-TG) also binds to GLUT receptors. The aim of this Phase I study was to evaluate the safety, biodistribution and dosimetry of 99mTcTc-TG. Twelve ...lymphoma patients were injected with 729 ± 102 MBq 99mTcTc-TG. Whole-body planar imaging was performed in 10 patients at 2, 4, 6 and 24 h after injection. In all 12 patients, SPECT/CT (at 2 h) and SPECT (at 4 and 6 h) imaging was performed. Vital signs and possible side effects were monitored during imaging and up to 7 days after injection. 99mTcTc-TG injections were well-tolerated and no side effects or alterations in blood and urine analyses data were observed. The highest absorbed dose was in the kidneys and urinary bladder wall, followed by the adrenals, prostate, bone marrow, lungs, myocardium, ovaries, uterus, liver and gall bladder wall. 99mTcTc-TG SPECT/CT revealed foci of high activity uptake in the lymph nodes of all nine patients with known nodal lesions. Extranodal lesions were detected in all nine cases. In one patient, a lesion in the humerus head, which was not detected by CT, was visualized using 99mTcTc-TG. Potentially, 99mTcTc-TG can be considered as an additional diagnostic method for imaging GLUT receptors in lymphoma patients.
Raman spectroscopy offers a rapid and nondestructive method for qualitatively and quantitatively analyzing the molecular structure of substances. Herein, a facile and cost‐effective approach for the ...preparation of three‐dimensional (3D) surface‐enhanced Raman scattering (SERS) substrates is proposed, in which pyramid structures are fabricated using silicon anisotropic wet etching and silver dendrites are decorated on these silicon pyramid (PSi) substrates by immersing them in a mixture of hydrofluoric acid and silver nitrate for several minutes. The 3D SERS substrates, based on PSi coated with Ag dendrites, reveal high‐performance SERS enhancement (with an analytical enhancement factor reaching 3.54 × 1010) and can detect rhodamine 6G (R6G) in the presence of chemical enhancer (lithium chloride) at low concentrations down to 10−11 m. For glucose detection, 2‐thienylboronic acid is employed to faciliate glucose attachment to the substrate surface, achieving a detection limit as low as 10−6 m. The substrate exhibits good repeatability with a relative standard deviation of 11.223%, as well as reusability and long‐term stability for detection. The results also highlight the excellent sensitivity of the PSi‐based SERS substrate, which is expected to be instrumental in biochemical analysis and holds significant potential for developing noninvasive glucose sensor for diabetic patients using saliva samples.
The three‐dimensional silver dendrites/silicon pyramid surface‐enhanced Raman scattering (SERS) substrates are successfully fabricated by anisotropic wet etching of a silicon wafer and chemical deposition in a mixed solution (HF/AgNO3). The proposed SERS substrates can detect glucose at ultralow concentrations below 10−6 m and exhibits high repeatability as well as reusability and long‐term stability for detection.
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