The role of reactive oxygen species in the antibacterial photodynamic treatment: photoinactivation vs proliferation.

UNLABELLED: Low-level light/low concentration of reactive oxygen species (ROS) may trigger some biochemical pathways that lead to cell proliferation. Thus, there is a risk of stimulation of bacterial cell proliferation during photodynamic therapy (PDT). In this study, PDT with different doses of 809-nm laser and indocyanine green (ICG) was investigated in vitro for safe bactericidal application. The combined effect of laser doses with ICG concentrations were examined on Pseudomonas aeruginosa in vitro. Data showed that low energy dose and ICG concentration caused bacterial cell proliferation. When these parameters were increased high enough, photoinactivation of the bacteria was achieved. Energy dose and photosensitizer concentration ranges at which proliferation, cell death or neither observed were determined. Furthermore, l-histidine was used as a scavenger of ROS to block the mechanism of biostimulation and cell killing. It inhibited proliferation when laser dose and ICG concentrations were low. It also inhibited cell killing when dose and concentration were high. Data showed that mechanisms of proliferation and cell killing depend on the amount of ROS and antibacterial photodynamic treatment have serious biostimulative risk. Effective range might need to be determined before any therapeutic usage. The risk seems to exist specifically at lower energy doses and photosensitizer concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: The main purpose in antibacterial photodynamic therapy (PDT) is to kill the micro-organisms that cannot be destroyed by conventional methods. Low-level light and/or low concentration of reactive oxygen species may trigger some biochemical pathways that lead to cell proliferation. Thus, there is a risk of bacterial cell proliferation during PDT. In this study we report that PDT with ICG application can induce biostimulation when laser dose and photosensitizer concentration are not optimized properly. Therefore, optimum dosimetry in PDT possesses great importance in the treatment of wounds infected by antibiotic-resistant bacteria.

The MEFV gene pathogenic variants and phenotype-genotype correlation in children with familial Mediterranean fever in the Çanakkale population.

The aim of the current study was to determine the frequency of the Mediterranean fever (MEFV) gene pathogenic variants in 60 children diagnosed with familial Mediterranean fever (FMF) and to compare the phenotype-genotype correlation. Genomic DNA was isolated by the spin-column method from peripheral blood samples (collected in vacutainers containing EDTA) and buccal smears. The MEFV gene profiles for the current FMF cohort were genotyped by pyrosequencing and direct Sanger sequencing techniques for the target pathogenic variants. The most prominent clinical symptoms were abdominal pain (53.4%), fever (23.4%) and arthritis (23.3%). Eighteen different pathogenic variants were identified and the most frequent were p.Met694Val (20.0%), p.Glu148Gln (13.3%), p.Met680 Ile (11.7%) and p.Arg202Gln (11.7%). Abdominal pain, fever and arthritis were the most common presenting clinical characteristics. Results showed that not only clinical characteristics, but also genotyping of the MEFV gene is needed to establish the correct diagnosis of FMF in children and other family members.

Effects of tenoxicam in experimental corrosive esophagitis model.

Esophageal stricture, one of the important complications of corrosive esophagus, develops following edema and granulation tissue that forms during and after the inflammatory reactions. Tenoxicam, a non-steroid anti-inflammatory drug with a long half-life, prevents various leukocyte functions including phagocyte and histamine secretion by inhibiting prostaglandin synthesis and removes various oxygen radicals in the region of inflammation. We designed this as a histopathological study using tenoxicam in rats for which we created a corrosive esophagus model. After necessary authorizations were obtained, the study was performed in Çanakkale 18 Mart University experimental animal laboratory. Twenty-four Wistar albino rats, weighing 220-240 g, were used for the experiment. Experimental animals were randomized into three groups: tenoxicam group (group T, n:8), control group (group C, n:8), and sham group (group S, n:8). Tenoxicam 0.5 mg/kg/day was administered to animals in group T, where esophageal burn was developed experimentally, 5 mg/kg 0.9% NaCL was administered i.p. to rats in group C for 15 days, once in 24 hours. No procedure was applied to rats in group S. After 15 days, all animals were sacrificed under general anesthesia and their esophagi were extracted. As a result of histopathological evaluation, inflammation and fibroblast proliferation was not observed in rats in the sham group (group S). Intense inflammation was observed in six rats (6+/2-) in the control group, and fibroblast proliferation was observed as 5+/3-. And in treatment groups, inflammation was evaluated as 3+/5-, and fibroblast proliferation as 3+/5-. In our study, histopathologic damage score was higher in the control group (P < 0.005). We deduce that tenoxicam can be useful in the treatment of caustic esophageal injuries in the acute phase, but think that these drugs require further researches and clinical studies before routine clinical use.

Protective effect of glucagon-like peptide-2 in experimental corrosive esophagitis.

Corrosive esophageal injuries are one of the life-threatening morbidities leading to esophageal stricture and perforation affecting all age groups but especially children due to accidental ingestions in this age group. Glucagon-like peptide-2 (GLP-2) is an intestinal polypeptide with potent anti-inflammatory effects. Its effects are studied in various studies but not in corrosive esophagitis. We aimed to investigate whether it has protective effect in experimental corrosive esophagitis, in the absence of existing studies into possible links. Twenty-four Wistar-albino rats, weighing 220-240 g, were randomized into three groups (n = 8 in each). First group is control, second one is sham operated, and the third one is treatment group. Median laparotomy was made in all groups. In sham and treatment groups, esophagus was loosened and suspended from 1 cm proximal to the esophageal junction. The esophagus segment between suspenders was exposed to 0.1 mL 5% NaOH for 10 seconds. In the treatment group, rats were given GLP-2 for 7 days intraperitoneally. After 7 days, all rats were sacrified and esophagi were totally removed. In the histopathologic examination, esophageal tissues were compared in terms of inflammation, muscularis mucosa injury, and collagen deposition of tunica muscularis. Histopathologic changes in the esophageal tissues of groups were compared. Histopathologic injury in the GLP-2 treated group was significantly less than sham group (P < 0.05). There was statistically significant healing in the GLP-2 treatment group. It is concluded that GLP-2 has a preventive effect on inflammation and collagen accumulation in an experimental corrosive esophagitis. In the light of the information that initial lesions in the early phase are predictors of complications, GLP-2 is a promising agent that has an anti-inflammatory effect in caustic injuries.