- Surgery of small anterior skull base meningiomas by endoscopic 5-aminolevulinic acid fluorescence-guidance (e- 5ALA- FGS): first clinical experiences. [Journal Article]
- WNWorld Neurosurg 2018 Nov 09
- CONCLUSIONS: Residual meningioma tissue on the far side of a key-hole approach, e.g. in the olfactory groove or at the optic canal is difficult to visualize. Visualization may be improved by an endoscope. So far, fluorescence-guidance by a microscope was limited by insufficient fluorescence signals in deep corridors. With a specially equipped 5-ALA fluorescence endoscope one may combine the advantages of both endoscopic vision and fluorescence-guidance. The present report demonstrates the usefulness of 5-ALA endoscopy for difficult to visualize areas.Endoscopic 5-ALA fluorescence guidance was shown to be feasible when resecting small and deep-seated skull base meningiomas via minimally invasive approaches. Based on this proof of principle, we encourage its evaluation for the middle or posterior fossa (e.g. internal auditory canal) and other difficult areas (behind neuro-vascular structures or the brainstem). Sensitivity and specificity of this method should be prospectively and systematically investigated.
- Hepatocellular carcinoma in acute hepatic porphyrias: A Damocles Sword. [Journal Article]
- MGMol Genet Metab 2018 Oct 09
- Porphyrias are inherited diseases with low penetrance affecting the heme biosynthesis pathway. Acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria (HCP) togethe...
Porphyrias are inherited diseases with low penetrance affecting the heme biosynthesis pathway. Acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria (HCP) together constitute the acute hepatic porphyrias (AHP). These diseases have been identified as risk factors for primary liver cancers (PLC), mainly hepatocellular carcinoma (HCC: range 87-100%) but also cholangiocarcinoma, alone or combination with HCC. In AHP, HCC annual incidence rates range from 0.16 to 0.35% according to the populations studied. Annual incidence rates are higher in Swedish and Norwegian patients, due to a founder effect. It increases above age 50. The pathophysiology could include both direct toxic effects of heme precursors, particularly δ-aminolevulinic acid (ALA), compound heterozygosity for genes implied in heme biosynthesis pathway or the loss of oxidative stress homeostasis due to a relative lack of heme. The high HCC incidence justifies radiological surveillance in AHP patients above age 50. Efforts are made to find new biological non-invasive markers. In this respect, we describe here the first report of PIVKA-II clinical utility in the follow-up of an AIP patient that develop an HCC. In this manuscript we reviewed the epidemiology, the physiopathology, and the screening strategy of HCC in AHP.
- Topical Application of 5-Aminolevulinic Acid Is Sufficient for Photodynamic Therapy on Vocal Folds. [Journal Article]
- LLaryngoscope 2018 Nov 08
- CONCLUSIONS: Topical PDT with laryngeal spraying of 20% 5-ALA solution achieves sufficient therapeutic effects and is potentially applicable for the treatment of vocal fold leukoplakia.
- Combined fluorescence using 5 aminolevulinic acid (5-ALA) and sodium fluorescein (Fl-Na) at glioblastoma border. Intra-operative findings and histopathological data about 3 newly diagnosed consecutive cases. [Journal Article]
- WNWorld Neurosurg 2018 Nov 01
- Fluorescence-guided glioblastoma surgery is an intra-operative technique developed in the last years. Two main compounds have been used so far: 5-amilovelulinic acid (5-ALA) and sodium fluorescein (F...
Fluorescence-guided glioblastoma surgery is an intra-operative technique developed in the last years. Two main compounds have been used so far: 5-amilovelulinic acid (5-ALA) and sodium fluorescein (Fl-Na). Despite large literature on both techniques, few data are available on the use of both compounds in the same patient.
- Photodynamic therapy in the treatment of oral leukoplakia: a systematic review. [Review]
- PPPhotodiagnosis Photodyn Ther 2018 Oct 31
- CONCLUSIONS: PDT seems to be a useful therapeutic strategy in the management of oral leukoplakia as a non-surgical treatment. Further RCTs with long follow-up period, standardized PDT parameters, and comparing efficacy of PDT with various therapies are expected to acquire definite conclusions.
- Strong correlation of ferrochelatase enzymatic activity with Mitoferrin-1 mRNA in lymphoblasts of patients with protoporphyria. [Journal Article]
- MGMol Genet Metab 2018 Oct 22
- Accumulation of protoporphyrin IX (PPIX) and Zn-PPIX, are the clinical hallmarks of protoporphyria. Phenotypic expression of protoporphyria is due to decreased activity of ferrochelatase (FECH) or to...
Accumulation of protoporphyrin IX (PPIX) and Zn-PPIX, are the clinical hallmarks of protoporphyria. Phenotypic expression of protoporphyria is due to decreased activity of ferrochelatase (FECH) or to increased activity of aminolevulinic acid synthase (ALAS) in red blood cells. Other genetic defects have been shown to contribute to disease severity including loss of function mutations in the mitochondrial AAA-ATPase, CLPX and mutations in the Iron-responsive element binding protein 2 (IRP2), in mice. It is clear that multiple paths lead to a common phenotype of excess plasma PPIX that causes a phototoxic reaction on sun exposed areas. In this study we examined the association between mitochondrial iron acquisition and utilization with activity of FECH. Our data show that there is a metabolic link between the activity FECH and levels of MFRN1 mRNA. We examined the correlation between FECH activity and MFRN1 mRNA in cell lines established from patients with the classical protoporphyria, porphyria due to defects in ALAS2 mutations. Our data confirm MFRN1 message levels positively correlated with FECH enzymatic activity in all cell types.
- Neat1-miRNA204-5p-PI3K-AKT axis as a potential mechanism for Photodynamic Therapy treated Colitis in Mice. [Journal Article]
- PPPhotodiagnosis Photodyn Ther 2018 Oct 29
- CONCLUSIONS: This study provides the first in vivo comprehensive lncRNA and miRNA microarray analysis after 5-ALA-PDT treatment in DSS-induced colitis, and it may help to develop novel lncRNA-miRNA-related therapeutic approaches, such as the Neat1-miRNA204-5p-PI3K-AKT axis, to further increase the efficiency of PDT in IBD.
- Acute hepatic porphyrias: Identification of 46 hydroxymethylbilane synthase, 11 coproporphyrinogen oxidase, and 20 protoporphyrinogen oxidase novel mutations. [Journal Article]
- MGMol Genet Metab 2018 Oct 26
- The acute hepatic porphyrias (AHPs) are inborn errors of heme biosynthesis, which include three autosomal dominant porphyrias, Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), and...
The acute hepatic porphyrias (AHPs) are inborn errors of heme biosynthesis, which include three autosomal dominant porphyrias, Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), and Variegate Porphyria (VP), and the ultra-rare autosomal recessive porphyria, δ-Aminolevulinic Acid Dehydratase Deficiency Porphyria (ADP). AIP, HCP, VP, and ADP each results from loss-of-function (LOF) mutations in their disease-causing genes: hydroxymethylbilane synthase (HMBS); coproporphyrinogen oxidase (CPOX); protoporphyrinogen oxidase (PPOX), and δ-aminolevulinic acid dehydratase (ALAD), respectively. During the 11-year period from January 1, 2007 through December 31, 2017, the Mount Sinai Porphyrias Diagnostic Laboratory diagnosed 315 unrelated AIP individuals with HMBS mutations, including 46 previously unreported mutations, 29 unrelated HCP individuals with CPOX mutations, including 11 previously unreported mutations, and 54 unrelated VP individuals with PPOX mutations, including 20 previously unreported mutations. Overall, of the 1692 unrelated individuals referred for AHP molecular diagnostic testing, 398 (23.5%) had an AHP mutation. Of the 650 family members of mutation-positive individuals tested for an autosomal dominant AHP, 304 (46.8%) had their respective family mutation. These data expand the molecular genetic heterogeneity of the AHPs and document the usefulness of molecular testing to confirm the positive biochemical findings in symptomatic patients and identify at-risk asymptomatic family members.
- Towards Initial Indications for a Thiol-Based Redox Control of Arabidopsis 5-Aminolevulinic Acid Dehydratase. [Journal Article]
- AAntioxidants (Basel) 2018 Oct 31; 7(11)
- Thiol-based redox control is one of the important posttranslational mechanisms of the tetrapyrrole biosynthesis pathway. Many enzymes of the pathway have been shown to interact with thioredoxin (TRX)...
Thiol-based redox control is one of the important posttranslational mechanisms of the tetrapyrrole biosynthesis pathway. Many enzymes of the pathway have been shown to interact with thioredoxin (TRX) and Nicotinamide adenine dinucleotide phosphate (NADPH)-dependent thioredoxin reductase C (NTRC). We examined the redox-dependency of 5-aminolevulinic acid dehydratase (ALAD), which catalyzed the conjugation of two 5-aminolevulinic acid (ALA) molecules to porphobilinogen. ALAD interacted with TRX f, TRX m and NTRC in chloroplasts. Consequently, less ALAD protein accumulated in the trx f1, ntrc and trx f1/ntrc mutants compared to wild-type control resulting in decreased ALAD activity. In a polyacrylamide gel under non-reducing conditions, ALAD monomers turned out to be present in reduced and two oxidized forms. The reduced and oxidized forms of ALAD differed in their catalytic activity. The addition of TRX stimulated ALAD activity. From our results it was concluded that (i) deficiency of the reducing power mainly affected the in planta stability of ALAD; and (ii) the reduced form of ALAD displayed increased enzymatic activity.
New Search Next
- 5-Aminolevulinic Acid Improves Nutrient Uptake and Endogenous Hormone Accumulation, Enhancing Low-Temperature Stress Tolerance in Cucumbers. [Journal Article]
- IJInt J Mol Sci 2018 Oct 29; 19(11)
- 5-aminolevulinic acid (ALA) increases plant tolerance to low-temperature stress, but the physiological and biochemical mechanisms that underlie its effects are not fully understood. To investigate th...
5-aminolevulinic acid (ALA) increases plant tolerance to low-temperature stress, but the physiological and biochemical mechanisms that underlie its effects are not fully understood. To investigate them, cucumber seedlings were treated with different ALA concentrations (0, 15, 30 and 45 mg/L ALA) and subjected to low temperatures (12/8 °C day/night temperature). The another group (RT; regular temperature) was exposed to normal temperature (28/18 °C day/night temperature). Low-temperature stress decreased plant height, root length, leaf area, dry mass accumulation and the strong seedling index (SSI), chlorophyll contents, photosynthesis, leaf and root nutrient contents, antioxidant enzymatic activities, and hormone accumulation. Exogenous ALA application significantly alleviated the inhibition of seedling growth and increased plant height, root length, hypocotyl diameter, leaf area, and dry mass accumulation under low-temperature stress. Moreover, ALA increased chlorophyll content (Chl a, Chl b, Chl a+b, and Carotenoids) and photosynthetic capacity, net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO₂ concentration (Ci), and transpiration rate (Tr), as well as the activities of superoxide dismutase (SOD), peroxidase (POD, catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) enzymes, while decreasing hydrogen peroxide (H₂O₂), superoxide (O₂•-), and malondialdehyde (MDA) contents under low-temperature stress. In addition, nutrient contents (N, P, K, Mg, Ca, Cu, Fe, Mn, and Zn) and endogenous hormones (JA, IAA, BR, iPA, and ZR) were enhanced in roots and leaves, and GA4 and ABA were decreased. Our results suggest the up-regulation of antioxidant enzyme activities, nutrient contents, and hormone accumulation with the application of ALA increases tolerance to low-temperature stress, leading to improved cucumber seedling performance.