Assessment of in vitro Cytotoxic, iNOS, Antioxidant and Photodynamic Antimicrobial Activities of Water-soluble Sulfonated Phthalocyanines.

In recent years, much effort has been devoted to the development of effective anticancer agents. In this manner, the utilization of water-soluble sulfonated phthalocyanines is crucial for many cancer cell lines. In this study, phthalonitrile and metallophthalocyanine compounds linked by benzenesulfonic acid groups have been prepared. Antimicrobial behaviors of those compounds were investigated by performing disk diffusion and photodynamic assays on gram-positive and negative bacteria. Indium phthalocyanine (InClPc) (3) showed inhibition activity against B. cereus, B. subtilis and S. aureus with disk diffusion assay. Also, gallium and indium phthalocyanines (2 and 3) exhibited inhibitory activity on both gram-positive and -negative microorganisms after light activation. Increasing the inhibitor concentration and light exposure time increased the inhibition activity for both molecules. GaClPc (2) demonstrated the maximum reducing power capacity among studied compounds, and CoPc (4) showed even better DPPH radical scavenging ability than the standard molecule Trolox at 2000 µg mL-1 concentration. The dose-dependent effect of compounds on cytotoxicity was studied against cancer cells PANC-1, MDA-MB-231, HepG2, A549, HeLa, CaCo-2 and non-tumorigenic cells HEK-293. All compounds showed no significant cytotoxic effect on any cell line up to the highest treated concentration at 50 µg mL-1 . However, all phthalocyanines had significant nitric oxide inhibition activity, and only in copper phthalocyanine (CuPc) (5), the MTT IC50 value was reached on LPS-activated RAW 264.7 macrophage cells. The lowest inducible nitric oxide synthase (iNOS) IC50 values were defined as 6 ± 1 µg mL-1 and 7 ± 0.5 µg mL-1 for CuPc (5) and InClPc (3), respectively.

Resveratrol inhibits Src tyrosine kinase, STAT3, and Wnt signaling pathway in collagen induced arthritis model.

Resveratrol, a phytochemical, acts several cellular signaling pathways and has anti-inflammatory potentials. The purpose of this study is to research the therapeutic effect of resveratrol in collagen-induced arthritis (CIA) model in rats and whether resveratrol affects the activities of signaling pathways those are potent pathogenic actors of rheumatoid arthritis. Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant in Wistar albino rats. One day after the onset of arthritis (day 14), resveratrol (20 mg/kg/day) was given via oral gavage, until day 29. The paws of the rats were obtained for further analysis. Tissue Wnt5a, mitogen-activated protein kinase (MAPK), Src tyrosine kinase and signal transducer, and activator of transcription-3 (STAT3) mRNA expressions were determined by real-time polymerase chain reaction. Resveratrol ameliorated the clinical and histopathological (perisynovial inflammation and cartilage-bone destruction) findings of inflammatory arthritis. The tissue mRNA expressions of Wnt5a, MAPK3, Src kinase, and STAT3 were increased in the sham group compared to the control group. Resveratrol supplement decreased their expressions. The present study shows that Src kinase, STAT3, and Wnt signaling pathway are active in the CIA model. Resveratrol inhibits these signaling pathways and ameliorates inflammatory arthritis. © 2018 BioFactors, 45(1):69-74, 2019.

Efficacies of vitamin D and omega-3 polyunsaturated fatty acids on experimental endometriosis.

OBJECTIVE: The aim of this study was to investigate the effects of 1,25-dihydroxyvitamin-D3 (vitamin D) and omega-3 polyunsaturated fatty acids (omega-3 PUFA) on experimentally induced endometriosis in a rat model. MATERIALS AND METHODS: A prospective, single-blind, randomized, controlled experimental study was performed on 30 Wistar female rats. Endometriosis was surgically induced by implanting endometrial tissue on the abdominal peritoneum. Four weeks later, a second laparotomy was performed to assess pre-treatment implant volumes and cytokine levels. The rats were randomized into three groups: vitamin D group (42 µg/kg/day), omega-3 PUFA group (450 mg/kg/day), and control group (saline 0.1 mL/rat/day). These treatments were administered for 4 weeks. At the end of treatment, a third laparotomy was performed for the assessment of cytokine levels, implant volumes (post-treatment) and implants were totally excised for histopathologic examination. Pre- and post-treatment volumes, cytokine levels within the groups, as well as stromal and glandular tissues between the groups were compared. RESULTS: The mean post-treatment volume was statistically significantly reduced in the omega-3 PUFA group (p=0.02) and the level of the interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF) in the peritoneal fluid were significantly decreased at the end of treatment in the omega-3 PUFA group (p=0.02, p=0.03, and p=0.03, respectively). In the vitamin D group, only IL-6 levels were significantly decreased. In the histopathologic examination, the glandular tissue and stromal tissue scores of the implants were significant lower in the omega-3 PUFA group (p=0.03 and p=0.02). CONCLUSION: Omega-3 PUFA caused significant regression of endometriotic implants. Vitamin D has not been as effective as omega-3 PUFA on endometriosis.

Effect of parenterally L-arginine supplementation on the respiratory distress syndrome in preterm newborns.

L-Arginine (L-Arg) is the precursor of nitric oxide which plays an important role on pulmonary circulation and pulmonary vascular tone. Earlier studies suggested that L-Arg levels in preterm newborns with respiratory distress syndrome (RDS) were low due to its consumption and L-Arg supplementation may reduce the severity of RDS. Our aim was detect the effect of the parenterally L-Arg supplementation on RDS severity. The subjects were chosen between preterm newborns (gestational age <34 weeks) (n = 30). Twenty of the subjects were diagnosed with permaturity and RDS, and 10 of the subjects were healthy preterm newborns. Ten of the subjects was taken L-Arg (1.5 mmol/kg/d) in addition to routine RDS treatment and assumed as "Group 1". In this group, daily L-Arg supplementation was started end of the first day, and continued at end of fifth day. The others of the subjects diagnosed with RDS was take routine RDS treatment and assumed as "Group 2". Healthy preterm newborns assumed as "Group 3". Blood collections for L-Arg levels via tandem mass spectrometry were made in first day and repeated on the seventh days. Oxygenation index was used to determine severity of RDS. L-Arg consentrations in Group 1 were 8.7 ± 4.1 µM/L and 11.9 ± 5.0 µM/L in first and seventh day, respectively. L-Arg consentrations were 12.6 ± 4.5 µM/Land 10.9 ± 5.4 µM/L in Group 2 and 8.6 ± 5.1 µM/L and 9.4 ± 4.1 µM/L in Group 3. There is no correlation between L-Arg concentrations and OI also duration of the mechanical ventilation of the subjects in patient groups (Group 1 and 2).

Evaluation of transforming growth factor-ß2 for radiation-induced diarrhea after pelvic radiotherapy.

AIMS AND BACKGROUND: Radiotherapy (RT) plays a central role in the management of cancers located in the abdomen and pelvis. However, radiation-induced toxicity remains a major concern for patients receiving RT to the abdominopelvic region. In this context, our study aims to evaluate the use of transforming growth factor (TGF)-ß2-enriched formula for amelioration of radiation-induced diarrhea for patients undergoing pelvic RT. METHODS AND STUDY DESIGN: Between September 2013 and September 2014, 86 malnourished patients undergoing RT for pelvic cancers who received oral nutritional supplementation with or without TGF-ß2-enriched formula were assessed retrospectively in 3 groups. Oral diphenoxylate-atropine tablets were used at onset of diarrhea in all groups. Kruskal-Wallis and chi-square tests were used in the comparison of continuous and categorical variables, respectively. RESULTS: Patients receiving nutritional supplemention with TGF-ß2-enriched formula (groups I and II) experienced a significantly lower median number of diarrhea episodes compared to patients receiving nutritional supplementation with other products (group III), which was statistically significant (p<0.05). Also, number of patients experiencing grade 2 and grade 3 diarrhea was significantly lower in groups I and II compared to group III (p<0.05). CONCLUSIONS: Nutritional supplemention with TGF-ß2-enriched formula offers amelioration of radiation-induced diarrhea for patients receiving pelvic RT. Since this is the first study assessing the use of nutritional supplementation with TGF-ß2-enriched formula for patients undergoing pelvic RT, future prospective studies are needed to confirm the results.

Outcomes of trimodality approach in the management of T2N0M0 bladder cancer.

AIMS AND BACKGROUND: The main objective of this study is to evaluate outcomes of bladder preservation treatment for patients with muscle-invasive bladder cancer. METHODS AND STUDY DESIGN: 38 patients with histologically proven muscle-invasive bladder cancer treated at our department between January 2008 and December 2013 were analyzed retrospectively. Age, gender, pathology, stage, 3-year overall survival, 3-year disease-free survival, radiotherapy (RT) dose, genitourinary and gastrointestinal toxicity scores and response evaluation of the patients were recorded. 3-year overall survival and 3-year disease-free survivals were calculated by Kaplan-Meier method along with the analysis of gender, pathology, stage and therapy response of the study group. RESULTS: 33 patients (86.8%) were managed with concomitant chemoradiotherapy whereas 5 patients (13.2%) received only radiation therapy due to renal insufficency and comorbid diseases. 6 (15.8%) out of 38 patients had partial response (PR) and remaining 32 (84.2%) patients experienced complete response (CR). The PR group underwent salvage cystectomy and CR group had been followed-up after radical radiotherapy. Mean age of the group was 70.9 (range 45-90) years. 26 of all patients were male (68.4%) and 12 were female (31.6%). Mean follow-up time after completion of radiotherapy was 24.7 months (range 12-40). Mean RT dose was 64 Gy (range 60-66). 3-year overall survival was 64% and 3-year disease free survival was 73%. CONCLUSIONS: Bladder preserving approach is an alternative definitive therapy solution to radical cystectomy in the treatment of muscle-invasive bladder cancer with less morbidity, preserved natural bladder, and high quality of life.

Investigation on malondialdehyde, S100B, and advanced oxidation protein product levels in significant hyperbilirubinemia and the effect of intensive phototherapy on these parameters.

BACKGROUND: The parameters of oxidative stress [advanced oxidation protein products (AOPPs), malondialdehyde (MDA), and S100B] and the effect of intensive phototherapy (PT) on these parameters have not been studied extensively in newborns with significant hyperbilirubinemia (SH). We aimed to measure the levels of MDA, S100B, and AOPPs in newborns with SH, and to compare newborns with healthy control newborns without hyperbilirubinemia on the basis of these parameters of oxidative stress. In addition, we investigated the effect of intensive PT on these parameters during the treatment of SH and report our findings for the first time in the literature. METHODS: The study was performed in newborns (n = 62) who underwent intensive PT because of SH. Newborns without jaundice constituted the control group (n = 30). Both groups were compared with respect to demographic characteristics and biochemical (laboratory) parameters including MDA, AOPPs, and S100B. MDA, AOPPs, and S100B were also compared before and after intensive PT in the PT group. In the study group, a correlation analysis of demographic characteristics; MDA, AOPP, and S100B values; and changes occurring in MDA, AOPPs, and S100B values due to the effect of intensive PT was performed. RESULTS: Serum total bilirubin, S100B, and MDA levels in the PT group before performing PT were significantly higher than those in the control group. In newborns receiving PT serum total bilirubin, MDA and AOPP levels decreased significantly after intensive PT. In correlation analysis, a statistically significant negative correlation was found only between the amount of bilirubin decrease with PT and AOPP levels after PT in the study group. CONCLUSION: Whether the significant decrease in MDA levels, which was higher prior to PT, is due to the decrease in serum bilirubin levels or due to the effect of intensive PT itself remains to be determined in further studies. The decrease in AOPP levels after PT implies that intensive PT has protective effects on oxidative stress.

Iodine deficiency: a probable cause of neural tube defect.

INTRODUCTION: Iodine deficiency is the most devastating event in developing brain in the fetus and neonate. Iodine is absolutely necessary on the myelination, neuronal differentiation, and formation of neural processes, synaptogenesis, and neuronal migration by thyroidal hormones throughout pregnancy and shortly after birth. Neural tube defects (NTD) form after third and fourth gestational weeks and their etiologies are multifactorial. CASE REPORT: We herein present a male newborn with iodine deficiency and thoracic neuroenteric cyst bound to a myelomeningocele via a pedinculi. We hypothesize that iodine deficiency may be a cause of NTD, and iodine supplementation in preconception and pregnancy may prevent NTD.

Guaiazulene: a new treatment option for recalcitrant diaper dermatitis in NICU patients.

AIM: Based on a maternal observation, we aimed to evaluate the treatment effectiveness of guaiazulene (GA) containing local pomade in the high-risk neonates with recalcitrant diaper dermatitis (RDD). METHODS: We included 30 NICU patients of RDD, with level II-III aged between 22 and 67 days. Study group patients (n = 20) were treated with GA containing local pomade (0.05 g/100 g). Control group consisted of patients who had extended antifungal treatment. A visual scale was used to assess the response to treatment at the end of a week. Scoring was done at the beginning of the treatment, on the first, third and seventh days. RESULTS: Statistically significant differences in visual scores were determined between the two groups at the initial and following days of the treatment. In study group, improvements at the first and third days of the treatment were better than those of control group. Additionally, complete recovery rate in study group was better than that in controls. CONCLUSION: Having beneficial but no adverse effects, GA containing local pomade provided rapid recovery in risky neonates with RDD, who required rapid improvement.

A novel mutation in the MC2R gene causing familial glucocorticoid deficiency type 1.

Familial glucocorticoid deficiency (FGD) or hereditary unresponsiveness to adrenocorticotropin (ACTH) is an autosomal recessive disorder characterized by isolated glucocorticoid deficiency associated with normal mineralocorticoid secretion. Mutations in genes encoding either ACTH receptor or melanocortin 2 receptor accessory protein are responsible for the disease in about 50% of cases, named FGD type 1 and type 2, respectively. Patients may present with hyperpigmentation, recurrent infections, failure to thrive, hypoglycemic seizures, and coma in infancy or early childhood. Here we report the case of a 17-day-old newborn diagnosed with FGD type 1 who presented with hyperbilirubinemia and hyperpigmentation, a sign which was erroneously assumed to be due to prolonged phototherapy by the referring physician. Hormone analysis showed low cortisol and high ACTH levels with normal serum electrolytes and renin-aldosterone axis. Genetic analysis revealed a novel homozygous melanocortin 2 receptor mutation p.Leu225Arg in the patient. The healthy parents were heterozygous for the mutation.

Does early treatment prevent deafness in thiamine-responsive megaloblastic anaemia syndrome?

Thiamine-responsive megaloblastic anaemia (TRMA; OMIM 249270) syndrome is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anaemia, and sensorineural deafness. Progressive hearing loss is one of the cardinal findings of the syndrome and is known to be irreversible. Whether the deafness in TRMA syndrome can be prevented is not yet known. Here, we report a four-month-old female infant diagnosed with TRMA syndrome at an early age. There was no hearing loss at the time of diagnosis. The patient's initial auditory evoked brainstem response measurements were normal. Although she was given thiamine supplementation regularly following the diagnosis, the patient developed moderate sensorineural hearing loss at 20 months of age, indicating that early diagnosis and treatment with oral thiamine (100 mg/day) could not prevent deafness in TRMA syndrome. It would be premature to draw general conclusions from one case, but we believe that further patient-based observations can shed light on the pathophysiology of this rare syndrome as well as prediction of its prognosis.

The role of tilt training in preventing recurrent syncope in patients with vasovagal syncope: a prospective and randomized study.

BACKGROUND: Recurrent vasovagal syncope (VVS) can be a severely disabling disorder that may lead to an important deterioration of quality of life because of the severity and recurrence of episodes. This study sought to investigate the effectiveness of repeated orthostatic self-training in preventing syncope in patients with recurrent VVS. METHODS: Eighty-two consecutive patients (mean age 41 +/- 4 years, 37 males) with recurrent VVS episodes and positive head-up tilt testing (HUT) were enrolled in this study. The patients were then randomized (1:1) to conventional therapy or conventional therapy plus additional tilt training sessions. The patients were followed for spontaneous syncope for one year. Primary end-points were the recurrence of syncope, the number of episodes, and the interval of time to the first recurrence. RESULTS: There were no significant differences of baseline clinical characteristics and parameters of HUT between the tilt training and control groups. The patients had 4 +/- 2/year syncopal episodes prior to the HUT. The mean follow-up after randomization was 12 +/- 2 months. Spontaneous syncope recurrence during follow-up was 56% (23 patients) versus 37% (15 patients) in the control and tilt training groups, respectively (P = 0.1). Time to first recurrence was also similar in both groups (70 +/- 20 days vs 50 +/- 15 days, P = 0.09). The frequency of recurrent syncopes was similar in all types of VVSs while the rate of episodes was significantly higher in control group in patients with vasodepressor type during follow-up period (32% vs 10%, P = 0.04). The mean number of recurrent syncope episodes was also similar in both groups (3 +/- 1 vs 2 +/- 1, P = 0.4). CONCLUSIONS: Tilt training was unable to influence the spontaneous syncope recurrence for recurrent VVS except for vasodepressor type.