Evaluating the effects of rifampin in the prevention of neurogenic symptoms and cardiac arrhythmias caused by the systemic toxicity of lidocaine in rats.

Lidocaine toxicity is caused by unintended intravascular injection or overdose. Lidocaine is metabolized in the liver by the CYP3A4 isoenzyme. The objective was to investigate if the administration of rifampin could accelerate animal recovery and reduce the symptoms of lidocaine toxicity by induction of the CYP3A4. Thirty-six male rats were divided into control and treatment groups, each containing three subgroups. The treatment group received oral rifampin suspension daily for 1 week. In all rats, 2.00% lidocaine was injected intravenously. The first subgroup was monitored for neurological symptoms. In the second subgroup, data were recorded after the electrode was placed in the right hippocampus. Electrocardiograms were taken from the third subgroup. CYP3A4 was measured using an ELISA kit. Neurological recovery was seen after 22 and 15 min in the control and treatment groups, respectively. Rifampin also caused a significant reduction in amplitude and number of field action potentials compared to the control group. Numerous cardiac arrhythmias were observed in the control group. The mean level of CYP3A4 in the treatment group was significantly higher than in the control group. In conclusion, oral rifampin could increase the synthesis of CYP3A4, therefore, the animal recovery from lidocaine toxicity was accelerated.

Assessing the environmental impact of gold production from double refractory ore in a large-scale facility.

Despite the strict environmental management regulations, there is still a considerable adverse impact on the ecosystem and human health when it comes to large-scale gold mining operations. Gold mining is an energy-intensive process that can discharge substantial quantities of chemicals combined with gaseous emissions into the environment. Considering gold mining's significant role in Nevada's economy and the growing concern about climate change, it's necessary to investigate the environmental burdens of this sector. To provide a comprehensive environmental perspective on the large-scale gold mining operations in Nevada, this study used a life cycle assessment (LCA) approach to evaluate the environmental burdens of gold production from double refractory ores in the roasting process. The Tool for Reduction and Assessment of Chemical and Other Environmental Impacts (TRACI) method was used to evaluate the categories of acidification, ozone depletion, global warming, smog, carcinogenics, non-carcinogenics, respiratory effects, and fossil fuel depletion. Results showed that major contributors to greenhouse gas (GHG) emissions were grinding and off-gas treatment stages being responsible for 34.80 % and 56.10 % of the total global warming, respectively. The carbon footprint for producing one kg of gold was 12,200 kg CO2-eq. Sensitivity analysis was also employed on electricity to observe the influence of electricity on key contributor stages. A 10 % change in electricity reduced the GHG emissions in crushing and grinding by 12.2 % and 7.10 %, respectively, while delivering an insignificant effect on the off-gas treatment. Significantly, this study stands as the first initiative to apply LCA in the North American mining industry, with a unique focus on the off-gas treatment post-roasting and its associated emissions. Our findings can serve as a foundational database, aiding stakeholders in making informed decisions and enhancing sustainable practices in the gold mining industry.

A systematic synthesis of expert opinion on effective policies to tackle bacterial resistance worldwide.

Actions that are taken to preserve effective antibacterial agents and eliminate transmission of resistant organisms are crucial to prevent a catastrophic postantibiotic era. In this systematic review, we searched and appraised relevant texts and expert opinions to determine effective strategies to tackle bacterial resistance worldwide. We considered expert opinions, consensus, current discourses, comments, assumptions or assertions and discussion papers published in English. We searched following databases for expert opinion-based literature: MEDLINE, CINAHL, ISI Web of Knowledge, SCOPUS, Cochrane Central Register of Controlled Trials and World Health Organization (WHO). We extracted the textual data from texts using a standardised data extraction tool. Textual pooling was not possible, so the conclusions were presented in a narrative form. Eighteen texts were included in this review. The findings show that, the most repeated policies and strategies include implementing and strengthening bacterial resistance surveillance, developing national guidelines, improving public awareness; enhancing home and everyday life hygiene; improving prescribing patterns, improving laboratories capacity, promoting innovation and research in new drugs and technology and strengthening coordination. This review systematically gathered strategies that were recommended by textual publications. To our knowledge, this was the first systematic review of text and opinion in the field of bacterial resistance. These results can be used by policymakers, hospital managers, and governments, alongside the results of quantitative and qualitative systematic reviews.

Assessment of hepatic oxidative damage, paraoxonase-1 activity, and lipid profile in cattle naturally infected with Ba7besia bigemina.

Naturally occurring Babesia bigemina infection in cattle is associated with changes in the status of oxidative stress, trace elements, sialic acid, and cholinesterase activity in blood. However, to date there is no description of hepatic damage in the infected animals. More importantly, the majority of the above-mentioned causative factors are synthesized or stored in the liver. Therefore, this study was undertaken to evaluate biomarkers of hepatic function, paraoxonase-1 activity, and lipid profile in 13 cattle infected with B. bigemina which did not respond to standard treatment. The animals were necropsied and the histopathology of the liver and DNA damage of hepatocytes were examined. Blood analysis revealed a significant parasitemia burden-dependent increase in the activities of hepatic enzymes and total bilirubin and a decrease in albumin concentrations in the infected cattle compared to the control ones. Paraoxonase-1 activity was remarkably lower in the infected animals than the control. A significant decrease in the blood concentrations of total cholesterol, low density lipoprotein, and high density lipoprotein and a significant increase in the triglyceride concentration were observed in the infected animals. Severe oxidative damages were also recorded in the haptic tissue evidenced by significant alterations in the activities of antioxidant enzymes, suppression of total antioxidant capacity, and oxidation of biomolecules. Congestion of blood vessels, bile duct hyperplasia, and hepatocyte necrosis were the evident histopathologic findings. Our results revealed significant changes in the indices of liver function in the diseased cattle, leading to the conclusion that the parasite can potentially cause liver dysfunction.

Beneficial effects of angiotensin converting enzyme inhibition on scopolamine-induced learning and memory impairment in rats, the roles of brain-derived neurotrophic factor, nitric oxide and neuroinflammation.

The effect of the brain-derived neurotrophic factor (BDNF), cytokines, and renin angiotensin system (RAS) on memory function have been demonstrated. In this study, the effects of RAS inhibitor captopril (Capto) on hippocampal BDNF, interleukin -6 (IL-6), oxidative stress indicators, and nitric oxide (NO) in scopolamine (Sco)-induced memory impairment in rats were examined. The groups were (1) control, (2) Sco in which Sco was applied 30 min prior to the behavioral tests, and (3-5) Sco-Capto 10, 50, and 100 groups, where Capto (10, 50, or 100 mg/kg), were applied 2 weeks prior to the experiment, as well as 30 min prior to each Sco injection. The Morris Water Maze (MWM) test was conducted, and BDNF, IL-6, NO metabolites, malondialdehyde (MDA), thiol, superoxide dismutase (SOD), and catalase (CAT) were measured. Sco increased the delay and distance to the platform in the MWM test (P < .01 to P < .001), while shortening the time and distance in the target area (P < .01 to P < .001). Additionally, Sco increased IL-6, NO metabolites, and MDA, while decreasing BDNF, thiol, SOD, and CAT (P < .01 to P < .001). Although the Capto reduced the latency and distance traveled to the platform (P < .05 to P < .001), it elevated the time and distance traveled in the target area (P < .05 to P < .01). Furthermore, Capto improved BDNF, thiol, SOD, and CAT levels, and decreased IL-6, NO metabolites, and MDA (P < .05 to P < .001). RAS has a role in learning and memory impairment due to cholinergic system dysfunction. The possible mechanism(s) are including its effects on BDNF, neuro-inflammation and oxidative stress.

Improvement of the clinical signs of gait abnormality after treatment with levothyroxine in a horse with shivering and hypothyroidism.

An 11-year-old Hanoverian gelding used for jumping was evaluated for gait abnormalities and hoof problems in the hindlimbs. Clinical examinations revealed signs consistent with shivers. A thyroid gland enlargement was noticed, baseline serum thyroid hormone (TH) concentrations were low, and a low response to thyrotropin-releasing hormone administration was observed. Hypothyroidism was suspected. The horse was treated with levothyroxine for 1 year. TH concentrations returned to the normal range by week 4 of treatment. Thirty weeks after the initiation of levothyroxine therapy, the gait abnormality improved. Our findings suggest that the assessment of thyroid status and especially of the subclinical thyroid gland disorders in horses affected with shivering, as well as evaluation of the effects of levothyroxine on the improvement of clinical signs could be promising in establishing the aetiopathogenesis and/or treatment of shivering in horses.

Mitochondrial delivery of microRNA mimic let-7b to NSCLC cells by PAMAM-based nanoparticles.

Many biological mechanisms including cellular metabolism and cell death are regulated by mitochondria known as powerhouse of the cell. Recently, let-7b, a tumour-suppressor microRNA has been detected in mitochondria of human cells targeting several mitochondrial-encoded respiratory chain genes. Triphenylphosphonium cation (TPP) is one of the major classes of mitochondriotropics that possess the ability of specifically targeting the mitochondria. PAMAM dendrimers are one of the most available agents in gene delivery due to their well-defined and beneficial features such as large density of surface functional groups. Hyaluronic acid (HA), a natural polysaccharide has been demonstrated to have the abilities such as good biocompatibility and targeting CD44 overexpressed receptors on non-small cell lung cancer (NSCLC) cells. In this research, let-7b-PAMAM (G5)-TPP and let-7b-PAMAM (G5)-TPP-HA nano-carriers were designed to deliver let-7b miRNA mimic to NSCLC cells' mitochondria as a novel way of cancer cells inhibition. Nano-carriers were capable of being successfully taken up by A549 cells and localised in mitochondria environment. Let-7b loaded nanoparticles reduced cell viability and induced apoptosis significantly. Expression of genes involved in mitochondrial oxidative function was decreased resulting in nanoparticles effect on mitochondria. Application of mitochondria targeted-miRNA delivery systems could regulate cellular functions to inhibit lung cancer.

Anthelmintic activity of crude powder and crude aqueous extract of Trachyspermum ammi on gastrointestinal nematodes in donkey (Equus asinus): An in vivo study.

ETHNOPHARMACOLOGICAL RELEVANCE: Trachyspermum ammi has been used traditionally as a popular ethnobotanical plant in human and animal parasitic infestations. Few scientific studies have been conducted on in vitro anthelmintic activity of T. ammi against various helminths and there is no study on its in vivo/in vitro anthelmintic properties against equine helminths. AIM OF THE STUDY: The present study aimed to evaluate in vivo anthelmintic activity of crude powder (CP) and crude aqueous extract (CAE) of T. ammi seeds against gastrointestinal nematodes in the donkey. MATERIALS AND METHODS: Thirty donkeys, naturally and severely infected with Strongyle-type nematodes, were randomly divided into six groups and administered orally with graded doses of CP and CAE at single dose as follow: Two groups were treated with 1 and 3 gkg-1 body weight of CP, two groups were treated with CAE at the equivalent dose rate 1 and 3 gkg-1 bw of CP and one group was treated with 200 µgkg-1 bw of Ivermectin 0.2% (Positive Control). One group received no medication (Negative Control). Efficacy was determined by faecal egg count reduction (FECR) test. The faecal samples were taken from the donkeys on days 7, 14 and 28 post-treatments (PT) and the egg per gram (EPG) of faeces was determined for each animal. FECR for donkeys treated with CP, CAE, and Ivermectin 0.2% was calculated on days 7, 14, and 28 PT. In the present study, CAE was analyzed using gas chromatography-mass spectrometry (GC-MS) to determine CAE chemical components. High-performance liquid chromatography (HPLC) using a marker (thymol) was applied to confirm the existence of thymol as an active principle. RESULTS: Based on the FECR findings, the maximum FECR (71.2%) was observed in the group treated with CAE3 on day 14 PT, while it was 66.2% for CP3 on the same day. The effects of different treatments (P < 0.001), time (P < 0.001) and their interactions (P < 0.05) on EPG showed a significant difference. A dose-dependent response in the anthelmintic activity of CP and CAE was observed. GC-MS analysis indicated that thymol was the major component of CAE (Area = 45.01%) with the respective peak at retention times (Rt) 10.41 min. On HPLC analysis of CAE, thymol was found to be the major constituent of CAE (Area = 58.76%) with the same Rt at 13.233 min. CONCLUSION: The present study indicated that both CP and CAE of T. ammi had the dose-dependent anthelmintic effects. Due to the development of drug resistance against synthetic anti-helminthics, T. ammi seems to be a promising alternative for the treatment and prevention of helminths in livestock.

Analysis of Iran's National Medical Education Evolution and Innovation Plan using the Michelle and Scott's model of policymaking.

INTRODUCTION: Lack of a clear policy for the development of health human resources has created inconsistencies. These imbalances are threats to the health system to achieve its goals. Therefore, the development of human resources through proper performance of higher education health system is an important part of the policy development process of the health sector. The present paper aims to introduce the methods applied for the compilation of evolution and innovation program of medical sciences training as well as the most important directions for evolution and innovation. METHODS: In this study, we evaluated the methodology for designing packages of Iran's higher education health system evolution and innovation. For this purpose, the evaluation of the policy process was conducted based on Michelle and Scott's policy process models. This policy evaluation model starts by problem identification and definition and continue by agenda setting, policy formation, legitimation, implementation, evaluation, and policy modification, using the proper feedback. Qualitative content analysis method was used as a research method for subjective interpretation of the content of the text data. RESULTS: Twelve policies, 68 strategies and their translation in the health system were adopted in a comprehensive plan for higher health education. Eleven practical packages were also developed in order to implement these policies as packages for reform and innovation in medical education. These packages were organized based on the IPOCC pattern. CONCLUSIONS: The lack of a comprehensive look at each project or program could bring about irreparableness consequences. However, the MoHME of Iran, relying on the integration of health higher education with health care system and comprehensive method used for transformation and innovation plan in the field of health higher education could take an important step towards improving the nation's health.

Semi-nested polymerase chain reaction-based detection of Babesia spp. in small ruminants from Northwest of Iran.

AIM: The present study aimed to detect Babesia ovis and Babesia motasi in the blood samples of sheep and goats from Northwest of Iran by the semi-nested polymerase chain reaction (PCR) technique. MATERIALS AND METHODS: A total of 166 whole blood samples (including 123 sheep and 43 goats) were collected. In the first stage, the PCR was performed to amplify a piece of 18S rRNA gene of Babesia and Theileria genera. Then, semi-nested PCR was carried out on all PCR products to differentiate B. ovis and B. motasi. RESULTS: The PCR indicated that totally, 19 (11.44%) out of 166 samples were positive for Babesia or Theileria spp. The semi-nested PCR showed that 38 samples (22.89%) were positive only for B. ovis. No significant association was found between the infection rate of B. ovis and age, gender and species of animals. CONCLUSION: In the present study, there was no evidence for B. motasi infection in small ruminants from Northwest of Iran. Therefore, B. ovis was the main causative agent of ovine Babesiosis in this region.

Internationalization of medical education in Iran: A way towards implementation of the plans of development and innovation in medical education.

INTRODUCTION: Academic institutions are the most important organizations for implementation of internationalization policies and practices for integrating an international, intercultural and global dimension in higher education system. Also, a globally increasing demand for higher education has been seen in the past two decades so that the number of students enrolled in higher education institutions in the worldwide nation-states has increased dramatically. The National Plan of International Development of Medical Education was designed with the aim of identifying available potentials in all the universities of medical sciences, encouraging the development of international standards of medical education, and planning for the utilization of the existing capacity in Islamic republic of Iran. METHODS: Authors have tried to review the several aspects of international activities in higher education in the world and describe national experiences and main policies in globalization of medical education in Iran within implementation of the National Plan for Development and Innovation in Medical Education. RESULTS: The findings of some global experiences provide the policy makers with clear directions in order to develop internationalization of higher education. CONCLUSION: The Program for International Development of Medical Education was designed by the Deputy of Education in the Ministry of Health and the effective implementation of this Program was so important for promotion of Iranian medical education. But there were some challenges in this regard; addressing them through inter-sectoral collaboration is one of the most important strategies for the development of internationalization of education in the field of medical sciences.

Doxorubicin-conjugated D-glucosamine- and folate- bi-functionalised InP/ZnS quantum dots for cancer cells imaging and therapy.

Nanoscaled quantum dots (QDs), with unique optical properties have been used for the development of theranostics. Here, InP/ZnS QDs were synthesised and functionalised with folate (QD-FA), D-glucosamine (QD-GA) or both (QD-FA-GA). The bi-functionalised QDs were further conjugated with doxorubicin (QD-FA-GA-DOX). Optimum Indium to fatty acid (In:MA) ratio was 1:3.5. Transmission electron microscopy (TEM) micrographs revealed spherical morphology for the QDs (11 nm). Energy-dispersive spectroscopy (EDS) spectrum confirmed the chemical composition of the QDs. MTT analysis in the OVCAR-3 cells treated with bare QDs, QD-FA, QD-GA, QD-FA-GA and QD-FA-GA-DOX (0.2 mg/mL of QDs) after 24 h indicated low toxicity for the bare QDs and functionalised QDs (about 80-90% cell viability). QD-FA-GA-DOX nanoparticles elicited toxicity in the cells. Cellular uptake of the engineered QDs were investigated in both folate receptor (FR)-positive OVCAR-3 cells and FR-negative A549 cells using fluorescence microscopy and FACS flow cytometry. The FA-functionalised QDs showed significantly higher uptake in the FR-positive OVCAR-3 cells, nonetheless the GA-functionalised QDs resulted in an indiscriminate uptake in both cell lines. In conclusion, our findings indicated that DOX-conjugated FA-armed QDs can be used as theranostics for simultaneous imaging and therapy of cancer.

Preparation, Optimization and Physicochemical Characterization of Aripiprazole Loaded Nano-porous in situ Forming Implant.

BACKGROUND: Multiple applications of antipsychotic agents are the main obstacle in the treatment of schizophrenia. Due to behavioral abnormalities, low compliance is observed in most of the psychotic patients. Designing of new drug delivery systems to overcome compliance problem seems to be necessary. In situ forming implants are a suitable choice for the delivery of antipsychotic agents due to their easy administration process and sustained release kinetics. OBJECTIVE: In this study, a novel poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) based nanoporous in situ implant system is developed for delivery of aripiprazole. METHODS: Entrapment efficiency, drug loading, rheological features, morphological characteristics and release profile of nano-porous in situ implant system are analyzed in this study. RESULTS: Entrapment efficiency and drug loading coefficient were modeled and impact of different experimental parameters was analyzed using D-optimal study. Entrapment efficiency and drug loading were optimized at 99.32% and 75.23%, respectively. Rheological analyses demonstrated that the developed formulation is a highly cross-linked gel with possible capability for controlled delivery of aripiprazole. According to the FTIR studies, aripiprazole was intact within polymer networks. SEM and light microscopic analyses proved the acceptable morphological characteristics of in situ gels. Release studies demonstrated a biphasic pattern of release. After initial burst release, a sustained pattern was observed for 18 days. The release data was fitted to Korsmeyer-Peppas model and release pattern was found out to be Fickian. In addition, the release profile was compared with novel pluroniccarrageenan based hydrogel system. CONCLUSION: PHBV based in situ forming implant seems to be a novel formulation for delivery of Aripiprazole.

Pluronic F127 polymeric micelles for co-delivery of paclitaxel and lapatinib against metastatic breast cancer: preparation, optimization and in vitro evaluation.

The aim of this study was to develop and characterize the paclitaxel (PTX)-lapatinib (LPT) loaded micelles for simultaneous delivery against metastatic breast cancer. Efflux pump-mediated drug resistance influences the efficacy of chemotherapeutic regimens. However, in the newly developed delivery system, LPT was selected to act as chemosensetizer. LPT increases the intracellular level of PTX by inhibition of efflux pumps. Pluronic F127 was selected for the preparation of the micelles, and its critical micelle concentration was determined to be 0.012 mg/ml. D-optimal design was used to analyze the impact of different experimental parameters on PTX and LPT encapsulation ratio. PTX encapsulation ratio was optimized at 68.3%, while LPT encapsulation ratio found to be 70.1%. Transmission electron microscope analyses demonstrate that micelles possess a good core-shell structure without any sharp edge. Laser scattering method results indicated that size of the optimized micelles is 64.81 nm with acceptable polydispersity index (0.309). In vitro release studies showed a sustain release pattern. PTX-LPT-loaded micelles suppressed the proliferation of resistant T-47D cell line (IC50 = 0.6 ± 0.1 µg/ml) compared to binary mixture of PTX and LPT (IC50 = 6.7 ± 1.2 µg/ml). Therefore, it is concluded that the developed formulation might increase the therapeutic efficacy in drug resistant metastatic breast cancer.

The effects of short term intravenous infusion of a soybean based lipid emulsion on some blood constituents in sheep: A preliminary study.

To evaluate the effect of intravenous infusion of a soybean based lipid emulsion (Lipovenoes 10%) on some blood constituents in sheep, a replicated 2 × 2 Latin square design experiment was conducted in four clinically healthy ewes. Lipid emulsion (LE group) or normal saline (NS group) was infused intravenously at a rate of 0.025 mL kg(-1) per min for 6 hr and the concentrations of blood triglyceride, glucose, insulin, calcium, magnesium, phosphorous, sodium and potassium were measured before (baseline) and then at timepoints 2, 4, 6, 12 and 24 hr after infusion. Compared to the baseline values and/or NS infusion, LE infusion resulted in a significant increase in the concentrations of triglyceride (p < 0.001), glucose (p < 0.01), calcium (p < 0.05), phosphorous (p < 0.01) and a significant decrease in insulin (p < 0.001) and magnesium (p < 0.05) concentrations. Compared to the baseline value, the homeostasis model of insulin resistance (HOMA-IR) index increased (p < 0.001) at timepoints 2 and 4 hr and abruptly decreased at timepoint six hr (p < 0.01) following LE infusion. In LE group, HOMA-IR values were significantly (p < 0.001) higher than those for NS group at timepoints 2 and 4 hr after infusion. Neither treatment nor time influenced serum sodium and potassium concentrations (p > 0.05). In conclusion, intravenous infusion of Lipovenoes temporarily influenced some blood constituents. Increased triglyceride concentrations were associated with an increase in HOMA-IR values indicating a state of insulin resistance. No remarkable adverse effect was observed following LE infusion and lipid based emulsions can be safely used in ruminants not suffering from extensive lipid mobilization.

Protective and antidiabetic effects of extract from Nigella sativa on blood glucose concentrations against streptozotocin (STZ)-induced diabetic in rats: an experimental study with histopathological evaluation.

BACKGROUND: Diabetes in humans induces chronic complications such as cardiovascular damage, cataracts and retinopathy, nephropathy and polyneuropathy. The most common animal model of human diabetes is streptozotocin (STZ)-induced diabetes in the rat. The present study investigated the effects of Nigella sativa hydroalcholic extract on glucose concentrations in streptozotocin (STZ) diabetic rats. METHODS: In this study Twenty-five Wister-Albino rats (aged 8-9 weeks and weighing 200-250 g) were tested. Rats were divided into five experimental groups (control, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with hydroalcholic extract of Nigella Sativa (NS) (5 mg/kg B.W, IP), treated STZ-diabetic with hydroalcholic extract of NS (10 mg/kg B.W., IP) and treated STZ-diabetic with hydroalcholic extract of NS (20 mg/kg B.W., IP and 32 days were evaluated to assess its effect on fasting blood glucose (FBG), and in different groups fasting blood glucose (FBG) and body weight (BW) were measured in the particular days (1, 16 and 32). At the end of the study, the animals were fasted overnight, anaesthetized with an intraperitoneal injection of sodium pentobarbital (60 mg/kg), and sacrificed for obtaining tissues samples (liver, pancreases). The number of islets and cells were counted and the islet diameters were determined by calibrated micrometer. The glycogen content in the liver was examined by Periodic Acid-Schiff (PAS) staining. RESULTS: Treatment with NS (5 mg/kg b.w.) markedly increased BW gain and the FBG level was significantly (p<0.001) reduced when compared to the control. Histopathological examination showed that the NS (5 mg/kg b.w.) partially recovered hepatic glycogen content and protected the great deal of the pancreatic islet cells. The number of islets, cells and islets diameter were found statistically significant when compared to the control (p<0.01, p<0.05). CONCLUSIONS: Higher doses of NS did not exhibit any therapeutic effect. These results showed that hydroalcholic extract of NS at low doses has hypoglycemic effect and ameliorative effect on regeneration of pancreatic islets and may be used as a therapeutic agent in the management of diabetes mellitus. The hypoglycemic effect observed could be due to amelioration of ß-cell, thus leading to increased insulin levels. Consequently, N. sativa may prove clinically useful in the treatment of diabetics and in the protection of ß-cells against streptozotocin. VIRTUAL SLIDE: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1845133011104231.

Evolution of endoscopic management of ectopic ureterocele: a new approach.

PURPOSE: We report the evolution of endoscopic treatment of ectopic ureteroceles from the unroofing technique to a novel approach using concomitant ureterocele double puncture and intraureterocele fulguration. We also compare the results of different endoscopic modalities at a single center. MATERIALS AND METHODS: We reviewed the records of 46 children with ectopic ureteroceles who were treated endoscopically between 1995 and 2005. The patients were divided into 2 main groups. Group 1 included 17 patients who underwent common endoscopic treatments, including ureterocele incision (4 patients), single ureterocele puncture (4), and single puncture with insertion of a Double-J stent (9). Group 2 included 29 children who underwent ureterocele double puncture and fulguration of the anterior and posterior walls of the collapsed ureterocele after insertion of a Double-J stent into both punctured sites. We also managed concomitant vesicoureteral reflux by endoscopic injection of tricalcium phosphate ceramic into the subureteral region. RESULTS: Total success rates in group 1 were 0%, 25% and 33% in patients who underwent ureterocele incision, single ureterocele puncture and single puncture with insertion of a stent, respectively. Total success rate in group 2 was 90% (p<0.05). New onset vesicoureteral reflux developed in 8 patients (47%) in group 1, of which 6 were in ureterocele moieties, and in 8 patients (28%) in group 2, with none in a ureterocele moiety (p<0.01). A total of 13 patients (76%) in group 1 required open surgical intervention, compared to 3 (10%) in group 2 (p<0.05). CONCLUSIONS: This new endoscopic approach is highly effective in the treatment of children with ectopic ureteroceles.

Intravesical injection of botulinum toxin type A: management of neuropathic bladder and bowel dysfunction in children with myelomeningocele.

OBJECTIVES: To evaluate the efficacy of botulinum toxin A in the treatment of children with detrusor hyperreflexia caused by myelomeningocele and the effects of this treatment on neuropathic bladder and bowel dysfunction. METHODS: In a prospective study, 26 children with myelomeningocele (20 boys and 6 girls, mean age 6.9 years) were included. All patients had been nonresponders to medical treatment and required clean intermittent catheterization. Under cystoscopic guidance, 10 IU/kg of botulinum toxin A was injected into the detrusor muscle, sparing the trigone and ureteral orifices. In each patient, urinary incontinence grade and improvement in parameters of interest in the evaluation of bowel dysfunction were assessed before and 4 months after injection. Conventional urodynamic studies to determine maximal bladder capacity and maximal detrusor pressure and voiding cystoureterography were also performed. RESULTS: Four months after procedure, 19 patients (73%) had become completely dry between clean intermittent catheterizations, and the total improvement in urine incontinence was 88%. The mean maximal detrusor pressure was decreased to 83.2 +/- 4.6 cm H2O from the baseline of 139.3 +/- 11.2 (P <0.01). The average maximal bladder capacity increased from 102.8 +/- 6.3 mL to 270.2 +/- 9.5 mL (P <0.01). Of the 15 patients who had varying degrees of vesicoureteral reflux before the procedure, 11 (73%) had decrease in the vesicoureteral reflux grade. Also, bowel dysfunction improved in 10 (66%) of the 15 patients. CONCLUSIONS: Botulinum toxin A appears to be a safe, minimally invasive procedure for the management of neuropathic bladder and bowel dysfunction in children with myelomeningocele.

In vitro release of clomipramine HCl and buprenorphine HCl from poly adipic anhydride (PAA) and poly trimethylene carbonate (PTMC) blends.

Controlled drug-delivery technology is concerned with the systematic release of a pharmaceutical agent to maintain a therapeutic level of the drug in the body for modulated and/or prolonged periods of time. This may be achieved by incorporating the therapeutic agent into a degradable polymer vehicle, which releases the agent continuously as the matrix erodes. In this study, poly trimethylene carbonate (PTMC), an aliphatic polycarbonate, and poly adipic anhydride (PAA), an aliphatic polyanhydride, were synthesized via melt condensation and ring-opening polymerization of trimethylene carbonate and adipic acid, respectively. The release of clomipramine HCl and buprenorphine HCl from discs prepared with the use of PTMC-PAA blends in phosphate buffer (pH 7.4) are also described. Clomipramine HCl and buprenorphine HCl were both used as hydrophilic drug models. Theoretical treatment of the data with the Peppas model revealed that release of clomipramine HCl (5%) in devices containing 70% PTMC or more followed a Fickian diffusion model. However, the releases of buprenorphine HCl (5%) in the same devices were anomalous. For devices containing 50% and more PAA, surface erosion may play a significant role in the release of both molecules.