BCA2 is differentially expressed in renal oncocytoma: an analysis of 158 renal neoplasms

The distinction between renal oncocytoma and renal cell carcinoma, especially chromophobe renal cell carcinoma and clear cell carcinoma with oncocytic features, is important due to the different biologic potentials of these tumors. RING E3 ligases have the subject of intense studies for their roles in many diseases including cancer and as potential therapeutic targets. All RING E3 ligases, including BCA2, contain a consensus protein sequence that would complex two or more zinc ions in the expressed protein. Identification of which ubiquitin ligases specifically affect distinct cellular processes is essential to the development of targeted therapeutics in these tumors. The ubiquitin–proteasome system regulates the turnover of proteins that have essential roles in the cell cycle, apoptosis, DNA damage repair, and in protein trafficking, which makes this pathway a target for oncogenic events. In this study, we investigated expression of BCA2 in renal oncocytoma and renal cell carcinoma. A total of 158 patients were included in the study. Our study has shown that 114/114 (100 %) cases of renal cell carcinoma were negative for BCA2. All 38 (100 %) cases of renal oncocytoma were positive for BCA2, and 6/6 (100 %) cases designated as oncocytic neoplasm which favor oncocytoma were also positive for BCA2. This is the first study to date evaluating the expression of BCA2 in renal oncocytoma. BCA2 could serve as a marker that may be utilized in the distinction between renal oncocytoma and its mimickers.     

Hypercalcemia in children receiving pharmacologic doses of vitamin D

Vitamin D deficiency causes rickets, requiring vitamin D at doses greater than daily dietary intake. Several treatment regimens are found in the literature, with wide dosing ranges, inconsistent monitoring schedules, and lack of age-specific guidelines. We describe 3 children, ages 2 weeks to 2 and 9/12 years, who recently presented to our institution with hypercalcemia and hypervitaminosis D (25-hydroxyvitamin D levels >75 ng/mL), associated with treatment of documented or suspected vitamin D-deficient rickets. The doses of vitamin D used were within accepted guidelines and believed to be safe. The patients required between 6 weeks and 6 months to correct the elevated serum calcium, with time to resolution of hypercalcemia related to age and peak serum calcium, but not to peak 25-hydroxyvitamin D level. With recent widespread use of vitamin D in larger dosages in the general population, we provide evidence that care must be taken when using pharmacologic dosing in small children. With limited dosing guidelines available on a per weight basis, the administration of dosages to infants that are often used in older children and adults has toxic potential, requiring a cautious approach in dose selection and careful follow-up. Dosage recommendations may need to be reassessed, in particular, where follow-up and monitoring may be compromised.     

Electrospun poly(epsilon-caprolactone)/gelatin nanofibrous scaffolds for nerve tissue engineering

Nerve tissue engineering is one of the most promising methods to restore nerve systems in human health care. Scaffold design has pivotal role in nerve tissue engineering. Polymer blending is one of the most effective methods for providing new, desirable biocomposites for tissue-engineering applications. Random and aligned PCL/gelatin biocomposite scaffolds were fabricated by varying the ratios of PCL and gelatin concentrations. Chemical and mechanical properties of PCL/gelatin nanofibrous scaffolds were measured by FTIR, porometry, contact angle and tensile measurements, while the in vitro biodegradability of the different nanofibrous scaffolds were evaluated too. PCL/gelatin 70:30 nanofiber was found to exhibit the most balanced properties to meet all the required specifications for nerve tissue and was used for in vitro culture of nerve stem cells (C17.2 cells). MTS assay and SEM results showed that the biocomposite of PCL/gelatin 70:30 nanofibrous scaffolds enhanced the nerve differentiation and proliferation compared to PCL nanofibrous scaffolds and acted as a positive cue to support neurite outgrowth. It was found that the direction of nerve cell elongation and neurite outgrowth on aligned nanofibrous scaffolds is parallel to the direction of fibers. PCL/gelatin 70:30 nanofibrous scaffolds proved to be a promising biomaterial suitable for nerve regeneration.     

Pathologic Evaluation of Appendectomy Specimens in Children: Is Routine Histopatholgic Examination Indicated?

Objective

Acute appendicitis is the most common cause of abdominal surgery in children. Similarity between signs and symptoms of appendicitis and other common pediatric illnesses, atypical manifestations of appendicitis in young children, and children''s inability to give precise explanation for their symptoms contribute to considerable delay in proper diagnosis and increased rate of perforation. Current study reports the surgical and pathological findings of appendectomies in the largest Children''s Hospital in Iran. It also evaluates whether common protocol for pathologic evaluation following appendectomy is beneficial.

Methods

Pathologic reports of 947 appendectomies, performed with the presumptive diagnosis of acute appendicitis, were gathered. Correlation between surgical and pathologic findings was assessed. Demographic characteristics of patients between surgical and pathological subgroups were also compared.

Findings

The mean age of participants was 6.9±3.5 years. Eighty seven (25.5%) children had abnormal pathological findings and normal surgical report. None of miscellaneous findings including appendicular carcinoid tumor 3 (0.3%), oxyuriasis 2 (0.2%), and mycobacterial infection 4 (0.5%) were recognizable during the surgery. Of all pathologically confirmed cases with perforated appendicitis, 9.7% were not detected during the surgery.

Conclusion

In current study, acute appendicitis was the most common pathological diagnosis, however, high normal appendectomy rate along with noticeable proportion of surgically missed perforated appendicitis and unusual histopathologies strongly supported routine histological examination.     

The influence of uric acid treatments on liver glutathione system prevent oxidative damages in experimental autoimmune encephalomyelitis mice

Recently we reported that antioxidant system in brain and spinal cord in experimental autoimmune encephalomyelitis (EAE) mice is mainly affected at early stages of the disease [M. Zargari, A. Allameh, M.H. Sanati, T. Tiraihi, S.H. Lavasani, O. Emadyan, Relationship between the clinical scoring and demyelination in central nervous system with total antioxidant capacity of plasma during experimental autoimmune encephalomyelitis development in mice, Neurosci. Lett. 412 (2007), 24–28]. The aim of the present study was to investigate the role of uric acid (UA) on antioxidant system in liver and plasma of EAE mice. EAE was induced in C57/BL6 mice (n = 60), followed by i.p. administration of UA (10 mg/kg BW) in 30 mice at three distinct clinical stages (A: prior to onset, B: after onset, C: after development of EAE). Livers were removed and processed for measurement of lipid peroxidation products, reduced glutathione (GSH), and glutathione S-transferase (GST) and total antioxidant capacity of plasma (FRAP). The results showed that lipid peroxidation products in liver of EAE mice was increased significantly (∼85%) as compared to normal. UA administration to EAE mice caused a significant suppression of liver lipid peroxidation products (∼45%) at early stages (A and B). There was an inverse relationship between lipid peroxidation and cellular GSH in liver. GSH was significantly depleted in mice liver during the EAE progression, but it was recovered (∼29%) when UA was injected before the onset of the disease (groups A and B). Plasma total antioxidant capacity was significantly decreased during the development of EAE, however it was subsided in mice treated with UA as compared to the corresponding controls (21%) in groups A and B. Elevated liver GST as a result of EAE induction was reversed in mice treated with UA particularly in groups A and B. These results indicate that hepatic glutathione system, particularly GST plays a major role in modulation of oxidative damages to central nervous system (CNS) during EAE induction. The positive response of antioxidant system to UA administration in EAE mice was corroborated with improvement of clinical manifestation of the animals.     

Comparison of conventional phototherapy and phototherapy along with Kangaroo mother care on cutaneous bilirubin of neonates with physiological jaundice

Background: One of the adjuvant and desirable therapies is skin contact between mother and baby or Kangaroo mother care (KMC) that is a cheap, accessible, relaxing, noninvasive and easy method. This study aimed to compare the effect of conventional phototherapy method and phototherapy along with KMC on cutaneous bilirubin in neonates with physiological jaundice.

Materials and methods: In this randomized clinical trial, all infants with physiological jaundice who referred for phototherapy to Mofid Hospital of Shahid Beheshti University of Medical Sciences, Tehran, Iran were selected by convenience sampling based on inclusion criteria and were randomly assigned into two groups of conventional phototherapy (n?=?35) and phototherapy along with KMC (n?=?35).

Results: The results showed that there was a significant difference in the average volume of skin bilirubin before treatment with cutaneous bilirubin every 24?h after treatment (p?p?=?.236). Mean duration of hospitalization of infants in the intervention group was significantly lower than the control group (2.09 versus 3.03 d, p?Conclusion: Although KMC along with phototherapy has a favorable effect on the reduction of cutaneous bilirubin in neonates with physiological jaundice, there are not significant differences in routine care. This may need to do KMC for a longer time (more than 1?h) which must be surveyed in the future studies. KMC was effective in reduction of the duration of hospitalization in jaundiced infants.     

The role of toll-like receptors in B-cell development and immunopathogenesis of common variable immunodeficiency

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immune deficiency and is characterized by hypogammaglobulinemia, defect in specific antibody response and increased susceptibility to recurrent infections, malignancy and autoimmunity. Patients with CVID often have defects in post-antigenic B-cell differentiation, with fewer memory B cells and impaired isotype switching. Toll-like receptors (TLRs) are expressed on various immune cells as key elements of innate and adaptive immunity. TLR signaling in B cells plays multiple roles in cell differentiation and activation, class-switch recombination and cytokine and antibody production. Moreover, recent studies have shown functional alteration of TLRs responses in CVID patients including poor cell proliferation, impaired upregulation of co-stimulatory molecules and failure in cytokine and immunoglobulin production. The purpose of the present review is to discuss the role of TLRs in B-cell development and function as well as their role in the immunopathogenesis of CVID.     

The Anti-Oxidant Effects of Ginger and Cinnamon on Spermatogenesis Dys-function of Diabetes Rats

Background

Diabetes rats have been linked to reproductive dysfunction and plant medicine has been shown to be effective in its treatment. Antioxidants have distinctive effects on spermatogenesis, sperm biology and oxidative stress, and changes in anti-oxidant capacity are considered to be involved in the pathogenesis of chronic diabetes mellitus. Ginger and cinnamon are strong anti-oxidants and have been shown to reduce oxidative stress in the long-term treatment of streptozotocin (STZ)-induced diabetes in animal models. The present study examined the influence of combined ginger and cinnamon on spermatogenesis in STZ-induced diabetes in male Wistar rats.

Materials and Methods

Animals (n = 80) were allocated randomly into eight groups, 10 each: Group 1: Control rats given only 5cc Normal saline (0.9% NaCl) daily;Group2: rats received ginger (100mg/kg/rat) daily; Group 3: rats received cinnamon (75mg/kg) daily; Group 4: rats received ginger and cinnamon, (100mg/kg/rat ginger and 75mg/kg cinnamon) daily; Group 5: Diabetic control rats received only normal saline. Group 6: Diabetic rats received 100mg/kg/day ginger; Group 7: Diabetic rats received 75mg /kg/ day cinnamon; Group 8: Diabetic rats received ginger and cinnamon (100mg/kg/day and 75mg/kg /day). Diabetes was induced with 55 mg/kg, single intra-peritoneal injection of STZ in all groups. At the end of the experiment (56th day), blood samples were taken for determination of testosterone, LH,FSH, total anti-oxidant capacity, and levels of malondialdehyde, SOD, Catalase and GPX. All rats were euthanized, testes were dissected out and spermatozoa were collected from the epididymis for analysis.

Results

Sperm numbers, percentages of sperm viability and motility, and total serum testosterone increased in ginger and cinnamon and combined ginger and cinnamon treated diabetic rats compared with control groups. Serum testosterone, LH and FSH were higher compared to control group and also serum anti-oxidants (TAC, SOD, GPX and catalase) all were increased at the end of treatment. Combined ginger and cinnamon showed more intense increase in all parameters compare to ginger and cinnamon alone. Most of the results were significant (P<0.05).

Conclusion

We concluded that combined ginger and cinnamon have significant beneficial effects on the sperm viability, motility, and serum total testosterone, LH,FSH and serum anti-oxidants'' level and could be effective for maintaining healthy sperm parameters and male reproductive function in diabetics.     

Intravesical electromotive administration of botulinum toxin type A in improving the bladder and bowel functions: Evidence for novel mechanism of action

Objective: To examine the hypothesis that what is the concomitant mechanism of action botulinum toxin type A (BoNTA) administration by intravesical electromotive into the bladder resulting in bladder function improvement. We also tried to confirm the possibility of retrograde trans-axonal transportation of toxin.Design: Animal study.Setting: Ten male rabbits were divided into two groups.Participants: Group 1 (G1) (n = 5) (BoNTA/EMDA), and group 2 (G2) (n = 5) the control group.Interventions: Animals in G1received 10 IU/Kg of intravesical BoNTA through a specific catheter for electromotive drug administration (BoNTA/EMDA). About 0.1–0.15 ml of toxin was diluted in 1 ml of distilled water. The maximum frequency of the device for drug solution delivery was set at 4 mA for 15 min. In G2 as the control group, the same procedure was performed to deliver normal saline to the bladder.Outcome measures: Multiple biopsies were taken from bladder’s contiguous structures one month postoperatively. The immunohistochemical (IHC) evaluation was performed with anti-clostridium botulinum toxoid type A mouse IgM monoclonal antibody.Results: In specimens of G1, BoNTA penetrated through muscular layers of the bladder wall and the staining was uniform in the urothelium, interstitium, and muscular layers. Positive IHC staining showed that BoNTA was traced in the upper and lower spinal cord in addition to pelvic nerve, sacral nerve plexus, intestine wall, and pelvic floor muscle. In G2, all the specimens were intact in IHC staining.Conclusions: The presence of BoNTA in lower and upper spinal cord suggests the possibility of retrograde trans-axonal transfer of toxin to lower and upper neural pathways which may result in simultaneous improvement in bladder and bowel functions.