Anticarcinogenic effects of halofuginone on lung-derived cancer cells.

Malignant mesothelioma is a rare but aggressive form of malignancy, which is difficult to diagnose and is resistant to current chemotherapeutic treatment options. Molecular techniques have been used to investigate the mechanisms of action and the beneficial therapeutic effects of halofuginone (HF) in several cancers but not malignant mesotheliomas. In this study, the antiproliferative and apoptotic effects of HF were investigated through its ability to deregulate EGFR downstream signalling cascade proteins in the pathologically aggressive malignant mesothelioma and non-small-cell lung cancer cells. We showed that administration of HF at nanomolar concentrations induced a dose-dependent reduction in the viability of cancer cells, made cell cycle arrest, inhibited proliferation of cancer cells via STAT3 and ERK1/2 pathways and triggered the apoptotic cascade via p38MAPK. We demonstrated that the apoptotic cell death mechanism was mediated by enhanced activation of caspase-3 and concomitant PARP cleavage, downregulation of Bcl-2 and upregulation of Bax in both malignant mesothelioma and lung cancer cells. In particular, we demonstrated that cancer cells were more sensitive to HF treatment than normal mesothelial cells. Taken together, this study suggests that HF exerts its anticancer effects in lung-derived cancers by targeting signal transduction pathways mainly through deregulation of ERK1/2, STAT3 and p38MAPK to reduce cancer cell viability, induce cell cycle arrest and apoptotic cell death. Thus, HF might be considered as a potential agent against malignant mesothelioma and/or lung cancer cells.

Nesfatin-1 ameliorates oxidative bowel injury in rats with necrotizing enterocolitis: The role of the microbiota composition and claudin-3 expression.

BACKGROUND AND PURPOSE: Ongoing high mortality due to necrotizing enterocolitis (NEC) necessitates the investigation of novel treatments to improve the outcome of the affected newborns. The aim was to elucidate the potential therapeutic impact of the nesfatin-1, a peptide with anti-inflammatory and anti-apoptotic effects in several inflammatory processes, on NEC-induced newborn rats. MATERIALS AND METHODS: Sprague-Dawley pups were separated from their mothers, fed with a hyperosmolar formula and exposed to hypoxia, while control pups had no intervention. NEC-induced pups received saline or nesfatin-1 (0.2 µg/kg/day) for 3 days, while some nesfatin-1 treated pups were injected with capsaicin (50 µg/g) for the chemical ablation of afferent neurons. On the 4th day, clinical state and macroscopic gut assessments were made. In intestines, immunohistochemical staining of cycloxygenase-2 (COX-2), nuclear factor (NF)-κB-p65 (RelA), vascular endothelial growth factor (VEGF), claudin-3 and zonula occludens-1 (ZO-1) were performed, while gene expressions of COX-2, occludin, claudin-3, NF-κB-p65 (RelA) and VEGF were determined using q-PCR. In fecal samples, relative abundance of bacteria was quantified by q-PCR. Biochemical evaluation of oxidant/antioxidant parameters was performed in both intestinal and cerebral tissues. RESULTS: Claudin-3 and ZO-1 immunoreactivity scores were significantly elevated in the nesfatin-1 treated control pups. Nesfatin-1 reduced NEC-induced high macroscopic and clinical scores, inhibited NF-κB-65 pathway and maintained the balance of oxidant/antioxidant systems. NEC increased the abundance of Proteobacteria with a concomitant reduction in Actinobacteria and Bacteroidetes, while nesfatin-1 treatment reversed these alterations. Modulatory effects of nesfatin-1 on microbiota and oxidative injury were partially reversed by capsaicin. Immunohistochemistry demonstrated that nesfatin-1 abolished NEC-induced reduction in claudin-3. Gene expressions of COX-2, NF-κB, occludin and claudin-3 were elevated in saline-treated NEC pups, while these up-regulated mRNA levels were not further altered in nesfatin-1-treated NEC pups. CONCLUSION: Nesfatin-1 could be regarded as a potential preventive agent for the treatment of NEC.

The effectiveness of non-operative treatment in high-grade liver and spleen injury in children.

BACKGROUND: Although a nonoperative treatment approach is preferred for blunt liver and spleen trauma in childhood, there are significant differences between clinics in the algorithms used. The approach to high-grade liver and spleen injury is still controversial, particularly as grade V liver and spleen injuries are not included in the American Pediatric Surgical Association guideline. The aim of this study was to present experience with a non-operative treatment approach to children with high-grade liver and spleen injuries. METHODS: Pediatric patients who were referred to Marmara University Hospital's emergency department between January 2012 and January 2017 due to liver and spleen injury related to blunt abdominal trauma and who were followed up in the clinic were included in the study. The data were analyzed retrospectively in terms of age, sex, type of trauma, degree of organ damage, accompanying organ damage, duration of intensive care unit (ICU) and hospital stay, need for transfusion, and treatment method (operative-nonoperative). Grade I, II, or III organ damage was classified as low-grade, while grade IV and V organ lesions were classified as high-grade. RESULTS: Of 2800 patients who were diagnosed by radiological imaging with liver and spleen injuries due to blunt abdominal trauma and hospitalized in the clinic, 88 were included in the study. Isolated liver injury was determined in 41 patients, while 39 had an isolated spleen injury, and 8 had injuries to both organs. An accompanying organ injury was observed in 30 (34%) patients. In all, 83 (94%) patients underwent non-operative treatment and a surgical approach was required for 5 patients (6%). Patients with high-grade liver injury had a significantly longer period of hospitalization, duration of ICU stay, and greater transfusion requirement, compared with patients with low-grade liver injury (p=0.001, 0.001, and 0.001, respectively). A surgical approach was more common among patients with a highgrade liver injury than for patients with a low-grade injury (p=0.045). There was no significant difference between patients with a high- or low-grade spleen injury in terms of age, sex, duration of hospitalization, duration of ICU stay, transfusion requirement, or accompanying organ injury (p=0.254, 0.739, 0.114, 0.135, 0.057, 0.721, respectively). Similarly, there was no significant difference in terms of non-surgical or surgical treatment approach between the patients with high-grade spleen injury and those with low-grade spleen injury (p=0.488). CONCLUSION: Non-operative treatment is a feasible treatment method in pediatric patients with a high-grade blunt liver or spleen injury. Nonetheless, pediatric surgeons should bear in mind that patients with high-grade liver damage may require more surgical treatment.

Positional installation of contrast (PIC) and Redo-PIC cystography for diagnosis of occult vesicoureteral reflux.

Karadeniz-Cerit K, Thomas DT, Ergun R, Yildiz N, Alpay H, Inanir S, Dagli ET, Tugtepe H. Positional installation of contrast (PIC) and Redo-PIC cystography for diagnosis of occult vesicoureteral reflux. Turk J Pediatr 2018; 60: 180-187. To evaluate the value of Positional Installation of Contrast (PIC) and Redo-PIC cystography in patients with febrile recurrent urinary tract infection (f-UTI) where voiding cystourethrogram (VCUG) was negative. Patients with recurrent f-UTI with no reflux on VCUG referred to the outpatient clinic of Pediatric Urology, between June 2011 and June 2016 were included in the study. A PIC cystography was performed in all patients. When reflux was found, subureteric injection was performed. Urinary cultures were used for follow-up. Patients that continued having f-UTI, received redo-PIC cystography. PIC cystography was performed on 42 patients. The average age of patients was 8.0±3.6 years. Vesicoureteral reflux (VUR) was detected in 41 patients. Average follow-up time after PIC cystography was 44.6 months. Thirty-three patients (80.5%) were free of f-UTI after PIC cystography and concurrent subureteric injection. Eight patients continued to have recurrent f-UTI. Six of these patients underwent redo-PIC cystography and PIC-VUR was demonstrated in all patients. After an average follow up of 30.9 months, no f-UTI was seen in these patients. The success rate of 80.5% (33/41) after 1st PIC cystography and subureteric injection increased to 95.1% (39/41) after redo-PIC cystography in six patients. Patients with recurrent f-UTIs without VUR on VCUG are an important challenge. PIC cystography is an important tool in demonstrating occult VUR in these patients. We advise that PIC cystography is performed in all patients with recurrent f-UTI with negative VCUG and redo-PIC cystography in patients who continue to have f-UTI after 1st PIC cystography and subureteric injection.

Laparoscopic approach for removing a coin trapped in Meckel's diverticulum.

Foreign body ingestion is a common problem in children. Most of these foreign bodies spontaneously pass through the gastrointestinal tract. When there is a persistent foreign body in the abdomen, it is impossible to make a diagnosis without exploration. We herein present the case of a child who was admitted to our hospital with a coin trapped in Meckel's diverticulum and our laparoscopic approach in this case. The diagnosis of Meckel's diverticulum should be considered when there is a prolonged lodgment of a foreign body in the right lower quadrant, and the laparoscopic approach is the preferred choice in these cases.

Post-traumatic stress disorder in mothers of children who have undergone cancer surgery.

BACKGROUND: The aim of this study was to investigate the rate of post-traumatic stress disorder (PTSD) and associated risk factors among mothers of children who underwent cancer surgery. METHOD: This cross-sectional, multi-center study included a total of 60 mothers whose children underwent major thoraco-abdominal surgery and were under follow up in the outpatient setting between February 2016 and May 2016. Clinical Data Form, Hospital Anxiety and Depression Scale (HADS), and Clinician-Administered PTSD scale were used. RESULTS: Of all participants, 13 (21.7%) were diagnosed with PTSD. These mothers had shorter duration of marriage, longer duration of hospital stay after surgery, and higher HADS scores, compared with the others without PTSD. Thoughts of guilt such as "I am being punished or tested" were more frequent in mothers with PTSD. Insomnia, irritability, concentration problems, and psychological reactivity were the most common symptoms. CONCLUSION: Post-traumatic stress disorder is a severe disorder that may worsen the daily functioning of mothers and may also have an unfavorable effect on child. It is therefore of utmost importance for clinicians to recognize PTSD and the associated risk factors in order to guide these parents.

Catheter-related Saccharomyces cerevisiae Fungemia Following Saccharomyces boulardii Probiotic Treatment: In a child in intensive care unit and review of the literature.

Although Saccharomyces boulardii is usually a non-pathogenic fungus, in rare occasions it can cause invasive infection in children. We present the case of an 8-year-old patient in pediatric surgical intensive care unit who developed S. cerevisiae fungemia following probiotic treatment containing S. boulardii. Caspofungin was not effective in this case and he was treated with amphotericin B. We want to emphasize that physicians should be careful about probiotic usage in critically ill patients.

Inguinal Hernia Containing Uterus, Fallopian Tube, and Ovary in a Premature Newborn.

A female infant weighing 2,200 g was delivered at 34 weeks of gestation by vaginal delivery. She presented with an irreducible mass in the left inguinal region at 32 days of age. An ultrasonography (US) was performed and an incarcerated hernia containing uterus, fallopian tube, and ovary was diagnosed preoperatively. Surgery was performed through an inguinal approach; the uterus, fallopian tube, and ovary were found in the hernia sac. High ligation and an additional repair of the internal inguinal ring were performed. Patent processus vaginalis was found during contralateral exploration and also closed. The postoperative course was uneventful. After one year of follow-up, there have been no signs of recurrence.

The effect of dorsal dartos flaps on complication rates in hypospadias repair: a randomised prospective study.

AIM: This study prospectively analysed the effect of using a dartos flap on the complication rates of TIPU (tubularised incised plate urethroplasty) in hypospadias repair. MATERIAL AND METHODS: Patients having TIPU repair for hypospadias at our university hospital between January 2010 and August 2013 were prospectively divided into two groups. Group 1 had TIPU repair with dorsal dartos flap, whereas group 2 had flapless repair. At the end of the follow-up period (mean 23.3 m, median 20.2), complication rates were compared between two groups. RESULTS: There were 107 patients in each group. The overall complication rate was 9.3%. The complication rates were 12.1% in group 1 (6 glans dehiscence and 7 fistula) and 6.5% in group 2 (2 glans dehiscence and 5 fistula). The differences between complication rates and fistula were statistically insignificant (p = 0.2511 and p = 0.7710, respectively). CONCLUSION: Our prospective and randomised study found that the use of dartos flaps in hypospadias offers no statistically significant advantage over flapless repair for complication rates.

Solid pseudopapillary tumor of the pancreas: a rare entity.

Solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm in children that mainly occurs in young females. We herein report a rare case of SPT arising from the tail of the pancreas. A 13-year-old girl was admitted to our clinic with abdominal pain and anorexia. A mass was palpated on the physical examination. A 90x72 mm, encapsulated, heterogeneous mass with solid and cystic components was defined on computerized tomography (CT). Distal pancreatectomy was performed during the operation. Histopathological examination revealed that the tumor was a SPT with negative surgical margins. A six-month follow-up after surgical resection showed no evidence of recurrent disease. SPT should always be considered in the differential diagnosis in a young female with a palpable mass.

The antifibrotic drug halofuginone reduces ischemia/reperfusion-induced oxidative renal damage in rats.

AIM: The objective of the present study was to evaluate the protective effects of halofuginone against renal ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: Male Wistar albino rats were unilaterally nephrectomized and the left renal pedicles were occluded for 45 min to induce ischemia and then reperfused for 6 h (early) or for 72 h (late). The rats were treated intraperitoneally with either halofuginone (100 µg/kg/day) or saline 30 min prior to ischemia and the dose was repeated in the late reperfusion groups. In the sham groups, rats underwent unilateral nephrectomy and were treated at similar time points. The animals were decapitated at either 6 h or 72 h of reperfusion and trunk blood and kidney samples were obtained. RESULTS: I/R injury increased renal malondialdehyde levels, myeloperoxidase activity and reactive oxygen radical levels, and decreased the renal glutathione content. Halofuginone treatment was found to reduce oxidative I/R injury and improve renal function in the rat kidney, as evidenced by reduced generation of reactive oxygen species, depressed lipid peroxidation and myeloperoxidase activity, and increased glutathione levels. CONCLUSIONS: The present findings demonstrate the anti-inflammatory and antioxidant effects of halofuginone in renal I/R injury, supporting its potential use where renal I/R injury is inevitable.