Nanoparticles and Nanostructured Films with TGF-ß3: Preparation, Characterization, and Efficacy.

TGF-ß3 has been reported to have a strong therapeutic efficacy in wound healing when externally administered, but TGF-ß3's active form is rapidly metabolized and removed from the body. Therefore, a drug delivery system that can provide a new non-toxic and an effective treatment that could be locally applied and also be able to protect the stability of the protein and provide controlled release is required. The aim of the study is to prepare and characterize nanoparticles and nanostructured films with TGF-ß3 and to evaluate in vitro cytotoxicity of the loaded nanoparticles. PCL-based films containing TGF-ß3 or TGF-ß3-loaded PLGA nanoparticles were prepared with non-toxic modified solvent displacement method. The particle size and protein loading efficiency of TGF-ß3-loaded PLGA nanoparticles were 204.9 ± 10.3 nm and 42.42 ± 2.03%, respectively. In vitro release studies of TGF-ß3-loaded PLGA nanoparticle formulations revealed that the protein was completely released from the nanoparticles at the end of 24 h. In vitro release profile of film formulation containing TGF-ß3-loaded nanoparticles was similar. TGF-ß3 released from nanoparticles do not have a significant effect on proliferation of HepG2 cells demonstrating their biocompatibility. Additionally, prepared films were tested with in vivo wound healing mouse model and showed to heal significantly faster and with improved scarring. PCL films loaded with TGF-ß3 or TGF-ß3 nanoparticles prepared in this study may be an effective treatment approach for wound healing therapy after injury.

Pharmacological Protection against Ischemia-Reperfusion Injury by Regulating the Nrf2-Keap1-ARE Signaling Pathway.

Ischemia/reperfusion (I/R) injury is associated with substantial clinical implications, including a wide range of organs such as the brain, kidneys, lungs, heart, and many others. I/R injury (IRI) occurs due to the tissue injury following the reestablishment of blood supply to ischemic tissues, leading to enhanced aseptic inflammation and stimulation of oxidative stress via reactive oxygen and nitrogen species (ROS/RNS). Since ROS causes membrane lipids' peroxidation, triggers loss of membrane integrity, denaturation of proteins, DNA damage, and cell death, oxidative stress plays a critical part in I/R pathogenesis. Therefore, ROS regulation could be a promising therapeutic strategy for IRI. In this context, Nrf2 (NF-E2-related factor 2) is a transcription factor that regulates the expression of several factors involved in the cellular defense against oxidative stress and inflammation, including heme oxygenase-1 (HO-1). Numerous studies have shown the potential role of the Nrf2/HO-1 pathway in IRI; thus, we will review the molecular aspects of Nrf2/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response element (ARE) signaling pathway in I/R, and we will also highlight the recent insights into targeting this pathway as a promising therapeutic strategy for preventing IRI.

Effects of endothelin receptor blockade and COX inhibition on intestinal I/R injury in a rat model: Experimental research.

BACKGROUND: Intestinal ischemia is a highly morbid and mortal condition with no specific treatment. The present study aimed to investigate the effects of cyclooxygenase (COX) inhibition synchronized with nitric oxide (NO) release and endothelin (ET) receptor blockade on oxidative stress, inflammation, vasoconstriction, and bacterial translocation which occur during ischemia-reperfusion (I/R) injury in in-vivo rat intestinal I/R model. MATERIALS AND METHODS: 36 male Wistar rats were randomly divided into six groups (n = 6). Superior mesenteric artery blood flow (SMABF) was recorded; SMA was occluded for 30 min; SMABF was re-recorded at the beginning of the reperfusion phase. Rats were sacrificed after the reperfusion period of 60 min. Blood and tissue samples were obtained. Acetylsalicylic acid (ASA), NO-ASA, flurbiprofen (FLUR), and Tezosentan (TS) were administered 15 min after ischemia. Histopathological examination, bacterial translocation, and biochemical analysis were performed in plasma and tissue samples. RESULTS: SMABF difference, mean Chiu's score and bacterial translocation were increased in the I/R group and decreased in the treatment groups. Plasma LDH, transaminases, intestinal fatty acid-binding protein (I-FABP), TNF-α, ICAM-1, interferon-gamma (IFN-Ɣ) and proinflammatory cytokine panel; tissue lipid peroxidation, MPO, xanthine oxidase (XO), NO, NF-kB levels and the expression of TNF-α were significantly elevated in the I/R group and markedly decreased in the treatment groups. The tissue antioxidant status was decreased in the I/R group and increased in the treatment groups. CONCLUSION: It is suggested that NO-ASA, TS, and FLUR can be introduced as promising therapeutics to improve intestinal I/R injury. INSTITUTIONAL PROTOCOL NO: 2018-29-05 (Animal Experimentations Ethics Committee, Hacettepe University).

Adult midgut malrotation presented with acute bowel obstruction and ischemia.

INTRODUCTION: Intestinal malrotation refers to the partial or complete failure of rotation of midgut around the superior mesenteric vessels in embryonic life. Arrested midgut rotation results due to narrow-based mesentery and increases the risk of twisting midgut and subsequent obstruction and necrosis. PRESENTATION OF CASE: 40 years old female patient admitted to emergency service with acute abdomen and computerized tomography scan showed dilated large and small intestine segments with air-fluid levels and twisted mesentery around superior mesenteric artery and vein indicating "whirpool sign". DISCUSSION: Malrotation in adults is a rare cause of midgut volvulus as though it should be considered in differential diagnosis in patients presented with acute abdomen and intestinal ischemia. Even though clinical symptoms are obscure, adult patients usually present with vomiting and recurrent abdominal pain due to chronic partial obstruction. Contrast enhanced radiograph has been shown to be the most accurate method. Typical radiological signs are corkscrew sign, which is caused by the dilatation of various duodenal segments at different levels and the relocation of duodenojejunal junction due to jejunum folding. As malrotation commonly causes intestinal obstruction, patients deserve an elective laparotomy. CONCLUSION: Malrotation should be considered in differential diagnosis in patients presented with acute abdomen and intestinal ischemia. Surgical intervention should be prompt to limit morbidity and mortality.

Crystallized phenol application and modified Limberg flap procedure in treatment of pilonidal sinus disease: A comparative retrospective study.

BACKGROUND/OBJECTIVE: Pilonidal sinus treatment includes various surgical and minimally invasive procedures, but there is still no standard treatment. Flap reconstructions and minimally invasive treatment options such as crystallized phenol application have recently been in the center of interest. The aim of this study is to compare crystallized phenol application as a minimally invasive treatment with modified Limberg flap reconstruction from many aspects. METHODS: Thirty-seven patients diagnosed with pilonidal sinus and treated with modified Limberg flap reconstruction, and 44 patients treated with crystallized phenol application were evaluated retrospectively in terms of age, sex, length of stay in hospital postoperatively, wound complications, and the cause and rate of recurrence. RESULTS: Length of hospital stay was decreased and no postoperative incision problems were found in the group treated with crystallized phenol application (p < 0.001 and p = 0.011, respectively). The difference between the groups in terms of recurrence rate was not statistically significant (p = 0.173). Although the recurrence rate was found to be higher in the patient group treated once with crystallized phenol application, the success rate following multiple applications of crystallized phenol was found to be 94.5%. Higher body mass index (> 24.9 kg/m(2)) and surgical site infection were strongly correlated with recurrence rate (p < 0.001). DISCUSSION: Crystallized phenol application is a good alternative to the modified Limberg flap procedure and other surgical procedures, because it has several advantages such as being a minimally invasive procedure performed under local anesthesia with higher success rate after multiple applications, decreased length of stay in hospital, and minimal scar tissue formation.

A serious conundrum for surgeons: Stump appendicitis.

Stump appendicitis is an acute inflammation of remnant appendix, a rare complication of incomplete appendectomy. It may present as acute abdomen with history of appendectomy, which may cause delay in diagnosis. Therefore, incomplete appendectomy should be considered as a differential diagnosis of acute abdomen in patients with medical history of appendectomy. The present case is one of stump appendicitis 6 months after appendectomy. Stump appendectomy was performed and the patient was discharged 7 days after the operation without any complication.

Endoscopic Removal of 15 Gastrointestinal Foreign Bodies.

Foreign body ingestion occurs commonly in children, elderly, mentally impaired or alcoholic, and psychiatric patients. We present a 15-year-old boy with mental retardation and uncontrolled psychiatric disorder admitted to the hospital with abdominal and chest pain. He was diagnosed with foreign body ingestion and 15 foreign objects, including a sharp knife, were successfully removed endoscopically by using an over-tube.

Adult Multicystic Nephroma: Case Report and Review of the Literature.

Multicystic nephroma (MCN) is relatively a rare, nongenetic and benign lesion of the kidney which has a bimodal distribution. The congenital form is commonly seen under the age of 2. Adult-onset MCN is more often seen in women, especially in post menopausal females. The aetiopathogenesis of MCN is still unknown. Ovarian-like stroma of the tumour indicates the tumour originates from the mullerian tissue of the kidney. Hormonal theory is suggestive as the stroma of the tumour is positive for estrogen and progesteron. Preoperative diagnosis of MCN is difficult. Surgical approach is recommended both for the histological diagnosis and the treatment of the disease. We here present a 53-year-old female patient with MCN admitted to the urology clinic with left flank pain treated successfully with partial nephrectomy. No recurrence was noted after six months of clinical and radiological follow-up.

Emergency thyroidectomy: Due to acute respiratory failure.

INTRODUCTION: Giant cervical and mediastinal goiter may lead to acute respiratory failure caused by laryngotracheal compression and airway obstruction. Here, we present a case admitted to the emergency service with a giant goiter along with respiratory failure and poor general health status, which required urgent surgical intervention. PRESENTATION OF CASE: A 71-year-old female admitted to the emergency room with shortness of breath and poor general health status resulting from a giant cervical swelling progressively increased during the last 7 years and constituted severe respiratory failure which has become severe in the last one month. A giant nodular goiter of the left thyroid lobe extending retrosternally, causing tracheal compression, limiting the neck movements was detected with clinical examination and bedside ultrasound. Emergency thyroidectomy was planned. Fiberoptic-assisted awake nasal intubation was performed in the operating room. Emergency total thyroidectomy was performed for the life-threatening respiratory failure. Postoperative period was uneventful. She was transferred from intensive care unit to the ward on postoperative day 3 and was discharged from the hospital on the postoperative 7th day. Benign multinodular hyperplasia was reported on the histopathological report. Patient was included in routine follow-up. DISCUSSION: In the present case tracheal destruction due to compression of the giant goiter was found in agreement with previous reports. Emergency thyroidectomy was performed after awake intubation since it is a common surgical option for the treatment of giant goiter causing severe airway obstruction. CONCLUSION: Respiratory failure due to giant nodular goiter is a life-threatening situation and should be treated immediately by performing awake endotracheal intubation following emergency total thyroidectomy.

Cholesterolosis in routine histopathological examination after cholecystectomy: what should a surgeon behold in the reports?

INTRODUCTION: Cholecystectomy is one of the most common surgical procedures. Postoperative investigation of cholecystectomy specimen has a great value since histopathological reports may document some entities with significant clinical consequences. The aim of this study was to evaluate the association between cholesterolosis and the reports indicating some histopathological alterations in symptomatic cholecystitis. METHODS: This paper is based on a retrospective study. Histopathological reports of 432 cholecystectomy specimens between January 2011 and June 2013 were reviewed. Three reports were excluded due to perioperative diagnosis of cancer. Reports of 429 cholecystectomy specimens of the acute and symptomatic chronic cholecystitis patients were analyzed. Standardization of the reporting was questioned. Age, gender, histopathological wall thickness of gallbladder, reporting rates of acute inflammation, cholesterolosis, polypoid lesions, epithelial hyperplasia, gastric or intestinal metaplasia, dysplasia and incidental cancer were investigated and compared between patients with and without cholesterolosis. Reported rates of histopathological findings were comparable between patients under and over 60 years old and patients with and without reported cholesterolosis. RESULTS: Reported histopathological findings were presented as acute inflammation in 46 (10.7%), cholesterolosis in 79 (18.4%), gallbladder polypoid lesions in 7 (1.6%), epithelial hyperplasia in 16 (3.7%), metaplasia of any type in 34 (7.9%) of 429 patients. Dysplasia was excluded whereas one incidental gallbladder carcinoma was reported. Epithelial hyperplasia and metaplasia were found to be related to age. Gallbladder wall thickness was decreased with cholesterolosis. However, only a correlation between cholesterolosis and gender or metaplasia was noted. CONCLUSION: Recent study suggests that cholesterolosis is somehow associated with metaplasia. Thus, surgeons should carefully interpret the histopathology reports based on unusual or exceptional findings corresponding to the cholecystectomy specimens. Any abnormal finding in the reports should be investigated in terms of the progress of the pathology and also its clinical consequences.

Spontaneous splenic artery aneurysm rupture: mimicking acute myocardial infarct.

Spontaneous splenic artery aneurysm (SAA) is a rare but a life-threatening condition. Thus, early diagnoses may increase the chance of survival. A 52-year-old female patient was admitted to the emergency department with a pain that starts from the chest and epigastric region and radiates to back and left arm. The patient prediagnosed as having acute myocardial infarct and was under observation when acute abdomen and hemorrhagic shock developed. After further investigation, the patient was diagnosed as having SAA and has undergone a successful surgery. The patient was fully cured and discharged from the hospital on the seventh postoperative day. The patient originally presented with SAA, although she was primarily observed in the emergency department with acute myocardial infarct diagnosis because of similar symptoms and clinical findings to cardiovascular diseases. When changes in the clinical picture occurred, the patient was reevaluated and had undergone an operation because of SAA rupture. Therefore, physicians should take into consideration of aneurysm rupture in the differential diagnosis of the cardiovascular conditions; otherwise, the patient may lose his/her life.