Combination of photodynamic therapy with 5-aminolaevulinic acid and microneedling in the treatment of alopecia areata resistant to conventional therapies: our experience with 41 patients.

Alopecia areata (AA) is a complex immune-mediated disorder, which is difficult to treat. The available treatment options seem to have limited benefit, help only some patients and have a high relapse rate. We evaluated a new therapeutic option for moderate to severe AA based on the combination of photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) and microneedling (MN). In total, 14 patients were enrolled, and these were randomly divided into 3 groups: Group A (MN alone; n = 9), Group B (ALA-PDT alone; n = 15) and Group C (combination of MN and ALA-PDT; n = 17). All patients were treated once every 3 weeks for a total of six treatments. The best clinical outcome was achieved in Group C, with complete hair regrowth observed in three patients, and an improvement of ≥ 50% and < 50% of the treated areas obtained in seven and six patients, respectively. Our report suggests that combination of ALA-PDT with MN could be an additional therapeutic option in moderate to severe AA, as MN allows better skin penetration of ALA and subsequent indirect immunosuppression.

Enhanced sterilization and healing of cutaneous pseudomonas infection using 5-aminolevulinic acid as a photosensitizer with 410-nm LED light.

BACKGROUND: Pseudomonas aeruginosa (PA) frequently develops antibiotic-resistant characteristics, which is clinically problematic. The main reason behind the rise of antibiotic-resistant PA is the extensive use of antibiotics. Therefore, a novel technique is needed to treat PA infections. Photodynamic therapy (PDT) is thought to have the potential to be a non-antibiotic treatment for infections. 5-Aminolevulinic acid (ALA), which works as a photosensitizer after being metabolized into protoporphyrin IX (PpIX) in the heme synthetic pathway, is used for PDT. Thus far, the in vivo effectiveness of PDT using ALA against PA is unknown. OBJECTIVE: In this study, we investigated PDT using ALA both in vitro and in vivo. METHODS AND RESULTS: Although PDT with ALA alone did not show a bactericidal effect on PA, PDT with both ALA and EDTA-2Na had a bactericidal effect in vitro. In in vivo experiments, wounds healed faster in PA-infected mice treated with PDT using both EDTA-2Na and ALA compared to non-PDT. CONCLUSION: These results suggest that PDT with EDTA-2Na and ALA is a potential novel treatment option for PA-infected wounds.

Modulating ALA-PDT efficacy of mutlidrug resistant MCF-7 breast cancer cells using ALA prodrug.

Multi-drug resistance of breast cancer is a major obstacle in chemotherapy of cancer treatments. Recently it was suggested that photodynamic therapy (PDT) can overcome drug resistance of tumors. ALA-PDT is based on the administration of 5-aminolevulinic acid (ALA), the natural precursor for the PpIX biosynthesis, which is a potent natural photosensitizer. In the present study we used the AlaAcBu, a multifunctional ALA-prodrug for photodynamic inactivation of drug resistant MCF-7/DOX breast cancer cells. Supplementation of low doses (0.2mM) of AlaAcBu to the cells significantly increased accumulation of PpIX in both MCF-7/WT and MCF-7/DOX cells in comparison to ALA, or ALA + butyric acid (BA). In addition, our results show that MCF-7/DOX cells are capable of producing higher levels of porphyrins than MCF-7/WT cells due to low expression of the enzyme ferrochelatase, which inserts iron into the tetra-pyrrol ring to form the end product heme. Light irradiation of the AlaAcBu treated cells activated efficient photodynamic killing of MCF-7/DOX cells similar to the parent MCF-7/WT cells, depicted by low mitochondrial enzymatic activity, LDH leakage and decreased cell survival following PDT. These results indicate that the pro-drug AlaAcBu is an effective ALA derivative for PDT treatments of multidrug resistant tumors.

[Lactic acidosis and accumulation of glutamate in the blood of neonates following treatment with calcium levulinate for hypocalcaemia]. / Lactaatacidose en glutamaatophoping in het bloed van neonaten na behandeling met calciumlevulaat wegens hypocalciëmie.

The data from 5 clinics concerning 8 infants, who had developed severe lactic acidosis and hyperglutamic acidaemia were reviewed. Blood-lactate levels were up to 15 mmol/l (reference level: < 2) and plasma-glutamate levels up to 1632 pmol/l (reference level: 14-78), and there was no concomitant hyperglutaminaemia (levels up to 1032 micromol/l (reference level: 333-809)). A positive correlation between the amount of calcium levulinate administered and the degree of hyperglutamic acidaemia was found. Replacement of the calcium levulinate by another calcium salt caused a reversal of the biochemical abnormalities of the patients. Two of the infants had a 22q11 microdeletion. This development of severe acidosis in infants who had been given a calcium supplement in the form of calcium levulinate may be related to genetic predisposition. The paradoxal hyperketonaemia and generalized aminoaciduria in 4 other patients suggested disturbed function ofthe mitochondrial respiratory chain. The hypothesis of the occurrence of an underlying defect of the mitochondrial respiratory chain was tested in the muscle tissue of one 22q11 patient, but this showed no abnormalities. Excessive accumulation of glutamate because of dysfunction ofglutamine synthetase, which forms glutamate from glutamine seems unlikely because of the relatively low values of plasma glutamate compared to the glutamine plasma levels. Calcium levulinate should no longer be used in neonates as it may lead to lactic acidosis.

[High-dosage oral magnesium therapy in arrhythmias. Results of an observational study in 1.160 patients with arrhythmia]. / Hochdosierte orale Magnesiumtherapie bei Herzrhythmusstörungen. Ergebnisse einer Anwendungsbeobachtung bei 1,160 Patienten mit Arrhythmie.

In the treatment of cardiac arrhythmias of varying genesis, an "observational study" in 1,160 patients showed that a high-dose oral magnesium preparation (Magnesium-Diasporal N 300 Granulat) was effective. In 82% of the patients observed, a dose of at least 300 mg magnesium/day produced good to very good results. Adverse effects of the drug were observed in only 1.6% of the patients. For all groups, the "success parameters" improved significantly. High-rate arrhythmias showed a better response to magnesium treatment than did low-rate arrhythmias, with a close correlation being found with the heart rate at the start of treatment. High-dose oral magnesium had a positive effect on concomitant hypertension. At a dosage of 300 mg treatment should be continued for at least 6 weeks.