Effects of transrectal medicinal ozone in horses - clinical and laboratory aspects / Efeitos do ozônio medicinal transretal em cavalos - aspectos clínicos e laboratoriais

Ozone (O3) therapy has been used for medical procedures for centuries; however, there are no extensive studies on its utilization in horses. This study aimed to evaluate the application of transrectal O3 on horses by physical and laboratorial evaluation, and production of reactive oxygen species (ROS). Sixteen healthy horses were separated in two groups: a control group (CG) and a group treated with O3 (TG). The TG animals received 1L of an oxygen and O3 mixture transrectally. The initial dose was 10µg/ml for the first two applications, 15µg/ml for the following two applications, and 20µg/ml for the next six applications. The CG animals received 1L of oxygen transrectally. In TG animals no variations in the physical examination were detected; furthermore, TG animals did not exhibit changes in biochemical evaluation results, fibrinogen concentrations, or ROS production. TG animals had increased red blood cell counts, hemoglobin concentrations, and packet cell volume values in comparison to the baseline and CG values. We could infer that O3 affected the red blood cell counts and improved rhetological properties of the blood. The transrectal application of O3 in horses is safe and can indirectly improve the oxygenation and metabolism of tissues.(AU)

A utilização medicinal do ozônio (O3) é secular, contudo não existem estudos expressivos de sua utilização em equinos. O objetivo deste estudo foi avaliar o efeito da aplicação transretal de O3 em equinos por meio da avaliação física, laboratorial, e produção de espécies reativas de oxigênio (EROs). Dezesseis equinos hígidos foram separados em dois grupos: grupo controle (GC) e grupo tratado com O3 (GT). O GT recebeu por via retal 1L da mistura de oxigênio e ozônio, sendo a dose inicial de 10µg/ml por duas aplicações, 15µg/ml por mais duas aplicações e 20µg/ml por seis aplicações. O GC recebeu 1L de oxigênio via transretal. No GT não foram observadas alterações no exame físico, bem como não foram observadas alterações na avaliação bioquímica, concentração de fibrinogênio e produção de EROs. O GT apresentou aumento no número de hemácias, na concentração de hemoglobina, e nos valores de hematócrito em relação aos valores basais e GC. Podemos inferir que o O3 alterou os valores de eritrócitos e melhorou as propriedades reológicas do sangue. Conclui-se que a aplicação transretal de 03 em equinos é segura e pode melhorar indiretamente a oxigenação e metabolismo dos tecidos.(AU)

EphrinB2 repression through ZEB2 mediates tumour invasion and anti-angiogenic resistance.

Diffuse invasion of the surrounding brain parenchyma is a major obstacle in the treatment of gliomas with various therapeutics, including anti-angiogenic agents. Here we identify the epi-/genetic and microenvironmental downregulation of ephrinB2 as a crucial step that promotes tumour invasion by abrogation of repulsive signals. We demonstrate that ephrinB2 is downregulated in human gliomas as a consequence of promoter hypermethylation and gene deletion. Consistently, genetic deletion of ephrinB2 in a murine high-grade glioma model increases invasion. Importantly, ephrinB2 gene silencing is complemented by a hypoxia-induced transcriptional repression. Mechanistically, hypoxia-inducible factor (HIF)-1α induces the EMT repressor ZEB2, which directly downregulates ephrinB2 through promoter binding to enhance tumour invasiveness. This mechanism is activated following anti-angiogenic treatment of gliomas and is efficiently blocked by disrupting ZEB2 activity. Taken together, our results identify ZEB2 as an attractive therapeutic target to inhibit tumour invasion and counteract tumour resistance mechanisms induced by anti-angiogenic treatment strategies.

PVDF-HFP/ether-modified polysiloxane membranes obtained via airbrush spraying as active separators for application in lithium ion batteries.

Improved hybrid polymer electrolyte membranes are introduced based on ether-modified polysiloxanes and poly(vinylidene fluoride-co-hexafluoropropylene) yielding a safe separator membrane, which is able to be sprayed directly onto lithium ion battery active materials, with an active role for enhanced ion transport.

High-Resolution Ultrasound for Diagnostic Assessment of the Great Auricular Nerve--Normal and First Pathologic Findings.

PURPOSE: The great auricular nerve (GAN) is a sensory branch of the superficial cervical plexus. While its blockade is an established procedure, little is known about the ultrasound appearance of pathologic conditions of the GAN itself. We, therefore, aimed to evaluate the possibility of the visualization and diagnostic assessment of the GAN along its entire course by means of high-resolution ultrasound (HRUS). MATERIALS AND METHODS: To assess the feasibility of visualization, we performed HRUS with an 18 MHz probe, HRUS-guided, fine-needle ink markings and consecutive dissection in six anatomical specimens. Then, we measured the diameter of the GAN in healthy volunteers and finally performed a retrospective review of patients referred for HRUS examinations because of pain within GAN territory between August 1, 2012 and August 1, 2013. RESULTS: The GAN was clearly visible with HRUS from its formation to the final branches, and was marked successfully on both sides in all anatomical specimens (n = 12). The mean average in-vivo was 0.14 cm ± 0.03 (range 0.08-0.2). Seven cases of patients with GAN pathologies of various origins (idiopathic, traumatic, tumorous and iatrogenic) were identified, of which 6 were visible on HRUS and all of which could be confirmed by complete resolution of symptoms after selective HRUS-guided GAN block. CONCLUSION: This study confirms the reliable ability to visualize the GAN with HRUS throughout its course, both in anatomical specimens and in vivo. The provided cases show that pathologies of the GAN seem to have a variety of causes and may not be rare. We, therefore, encourage the use of HRUS in patients with unclear pain in the auricular, periauricular and posterior-lateral head.

Disruption of nigrostriatal and cerebellothalamic pathways in dopamine responsive Holmes' tremor.

Holmes' tremor is an unusual combination of rest, postural and kinetic tremor of the extremities. Medical treatment of this condition still remains unsatisfactory. The case of a 20-year-old female patient is reported who developed right-sided Holmes' tremor 9 months after a left-sided, cavernoma induced midbrain/pontine haemorrhage at the age of 16 years. Beta-CIT single photon emission computed tomography revealed abolished dopamine transporter activity in the left basal ganglia and striatum, in accordance with missing ipsilateral tegmento-frontal connectivity (medial forebrain bundle), demonstrated by diffusion tensor MRI. Tractography showed reduced fibre connectivity of the superior and middle cerebellar peduncles on the lesioned side. Administration of pramipexole and L-DOPA led to a clinically significant reduction in tremor severity. In conclusion, our results support the notion that Holmes' tremor was a result of diminished striatal dopaminergic input in our patient.

[Surgical management, prognostic factors, and outcome in hepatic trauma]. / Chirurgische Therapie, prognostische Faktoren und Ergebnisse beim Lebertrauma.

Hepatic trauma is a rare surgical emergency with significant morbidity and mortality. Extensive experience in liver surgery is a prerequisite for the management of these injuries. The medical records of 68 consecutive patients with hepatic trauma were retrospectively reviewed for the severity of liver injury, management, morbidity, mortality, and risk factors. Of the patients, 14 were treated conservatively and 52 surgically (24 suture/fibrin glue, 16 perihepatic packing, 11 resections, 1 liver transplantation). Two patients died just before emergency surgery could be performed. Overall mortality was 21% (14/68), and 13, 14, 6, 27, and 50% for types I, II, III, IV, and V injuries, respectively. Only nine deaths (all type IV and V) were liver related, while four were caused by extrahepatic injuries and one by concomitant liver cirrhosis. With respect to treatment, conservative management, suture, and resection had a low mortality of 0, 4, and 9%, respectively. In contrast, mortality was 47% in patients in whom only packing was performed (in severe injuries). Stepwise multivariate regression analysis proved prothrombin values <40%, ISS scores >30, and transfusion requirements of more than 10 red packed cells to be significant risk factors for post-traumatic death. Type I-III hepatic injuries can safely be treated by conservative or simple surgical means. However, complex hepatic injuries (types IV and V) carry a significant mortality and may require hepatic surgery, including liver resection or even transplantation. Therefore, patients with severe hepatic injuries should be treated in a specialized institution.

Activation of the Ah receptor signaling pathway by prostaglandins.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of a diverse range of chemicals, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin). Although no endogenous physiological ligand for the AhR has yet been described, numerous studies support the existence of such a ligand(s). Here we have examined the ability of prostaglandins and related chemicals to activate the AhR signaling system. Using two AhR-based bioassay systems we report that relatively high concentrations of several prostaglandins (namely, PGB3, PGD3, PGF3alpha, PGG2, PGH1, and PGH2) can not only stimulate AhR transformation and DNA binding in vitro, but also induce AhR-dependent reporter gene expression in mouse hepatoma cells in culture. PGG2 also induced AhR-dependent reporter gene expression to a level three-to four fold greater than that observed with a maximal inducing dose of TCDD. Sucrose gradient ligand binding analysis revealed that PGG2 could competitively displace [3H]TCDD from the AhR. Overall, our results demonstrate that selected prostaglandins are weak agonists for the AhR and they represent a structurally distinct and novel class of activator of the AhR signal transduction pathway.

Bile duct injury following laparoscopic cholecystectomy: a cause for continued concern.

Previous reports suggest that bile duct injuries sustained during laparoscopic cholecystectomy (lap chole) are frequently severe and related to cautery and high clip ligation. We performed a review of patients who sustained bile duct injury from lap chole since 1990 and assessed time to injury recognition, time to referral, Bismuth classification, initial and subsequent repairs, rate of recurrence, and length of follow-up. Seventy-four patients [median age 44 years, 58 of 74 female (78%)] were referred with a bile duct injury after lap chole. The level of injury was evenly divided between the bile duct bifurcation and the common hepatic duct: Bismuth III, IV, and V (40 of 74, 54%) versus Bismuth I and II (34 of 74, 46%). Concomitant hepatic arterial injury was identified in nine (12%) patients. Patients referred early after bile duct injury and requiring operative intervention underwent hepaticojejunostomy at a median of 2 days after referral. After surgical reconstruction at our center there has been an overall success rate of 89 per cent with no need for reintervention. Six (10%) of these patients have required one additional balloon dilatation at a mean follow-up of >24 months. One (2%) patient underwent biliary-enteric revision in follow-up. In patients with bile duct injury, stricture repair without delay was successful in the majority of patients treated in this series. Only one of 64 patients reconstructed at our center has required reoperation; six others have required a single balloon dilatation with subsequent good or excellent results. The majority of patients treated with operative repair at an experienced center can expect good long-term results with rare need for reintervention.

Ileoanal pouch versus ileostomy: is there a difference in quality of life?

Ileoanal pouch (IAP) construction is arguably the procedure of choice to follow proctocolectomy for ulcerative colitis (UC) or familial adenomatous polyposis (FAP). Patients with UC or FAP at our institution choose their operation after counseling with the surgeon, with an enterostomal therapist, and with patients who have undergone IAP and proctocolectomy with ileostomy (IL). We studied these patients who chose IAP and IL, to determine differences in outcome and quality of life (QOL) between those two groups. We assessed outcomes by evaluating clinic and hospital records and surveyed patients' QOL via a standardized questionnaire. During a retrospective 10-year study period, 86 patients underwent evaluation for IAP construction for UC (64) and FAP (22). Fifty-five patients underwent IAP construction, and 31 underwent IL. There were no operative deaths. Thirty-four patients sustained 69 early and late complications (40%). The IAP group experienced a higher complication rate, 53 per cent, compared with the IL group, 16 per cent. Forty-five patients (56%) have completed questionnaires. Eighty-seven per cent of IAP patients and 93 per cent of IL patients responded that their overall QOL is "always" better since their operation (P = not significant). Both groups reported very favorable responses to questions regarding work, social life, family life, sleep, and relationships without statistically significant differences between the two groups. Despite a high complication rate, IAP is an excellent operation for many patients with UC or FAP, but patients who choose IL after preoperative counseling can be expected to have similar improvement in quality of life.

Ah receptor-based chemical screening bioassays: application and limitations for the detection of Ah receptor agonists.

The aromatic hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates many of the biologic and toxicologic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related chemicals. Here we utilized two AhR-dependent bioassay systems as screening tools to identify novel AhR agonists and to detect the presence of AhR agonists in sample extracts. These assays measure the ability of a chemical to activate AhR DNA binding in vitro (GRAB bioassay) or AhR-dependent (luciferase) gene expression in cultured cells (CALUX bioassay). Known AhR agonists (halogenated and nonhalogenated aromatic hydrocarbons) were positive in both assays, whereas the AhR antagonist alpha-naphthoflavone exhibited agonist activity only in the GRAB assay. In vitro GRAB analysis has identified several imidazoline receptor ligands and beta-carbolines as AhR agonists and also revealed the presence of AhR agonist activity in crude DMSO extracts of commercial newspapers. In contrast to their positive activity in the GRAB assay, the majority of these chemicals/extracts were only weakly active or inactive in the cell-based CALUX assay. Our results not only reveal that the ability of a chemical to activate the AhR in vitro does not necessarily correlate with its ability to induce gene expression in intact cells, but the high level of false positives obtained with the GRAB assay clearly demonstrates its inability to accurately identify AhR agonists or agonist activity. Screening of unknown chemicals, chemical classes, and samples for AhR agonist activity will require the use of intact cell bioassays.

Noninvasive detection of ischemic bowel.

PURPOSE: Acute mesenteric arterial occlusion is an abdominal catastrophe that carries high morbidity and mortality rates. Current diagnostic methods, however, lack sensitivity and specificity and do not provide information about the viability of the affected bowel. Early diagnosis and intervention would improve patient outcomes and survival rates. The basic electrical rhythm (BER) is the omnipresent electrical slow wave of the gastrointestinal tract that characterizes the underlying electrical activity of the bowel. BER frequency is known to fall with ischemia. Superconducting quantum interference devices (SQUIDs) can detect BER by measuring the magnetic fields generated by the electrical activity of the smooth muscle of the small bowel. The purpose of this study was to determine the ability of a SQUID to detect mesenteric ischemia in a free-lying section of small bowel in an animal model of acute superior mesenteric artery occlusion. METHODS: Seven adult male rabbits (six experimental and one control) were studied with transabdominal SQUID and electrode recordings during baseline and after the induction of mesenteric ischemia with balloon occlusion of the superior mesenteric artery. Continuous recordings were taken for 120 minutes of ischemia and analyzed with autoregressive spectral analysis to determine the BER frequency during specific time points of the study. Two independent investigators blinded to the experimental preparation examined the results to determine whether there was decreased BER frequency and thus ischemia. The results are expressed as mean +/- SEM, and paired t tests were used to determine statistical significance. RESULTS: BER was detected in all seven animals and fell from 10.7 +/- 0.5 cpm to 7.0 +/- 1.8 cpm after 30 minutes of ischemia in the magnetic channels (P <.05, with t test). The fall in BER was detected by the SQUID in all six experimental animals. The blinded observers correctly identified healthy and ischemic magnetic data recording, with a sensitivity of 94% and specificity of 100%. CONCLUSION: SQUIDs can noninvasively detect bowel ischemia early in a free-lying segment of small bowel in this animal model with a high degree of sensitivity and specificity.

Ileoanal pouch procedures: clinical outcomes and quality-of-life assessment.

Ileoanal pouch (IAP) anastomosis following total colectomy for ulcerative colitis or familial adenomatous polyposis is performed with the goal of avoiding a permanent ileostomy and its effects on life satisfaction. During a retrospective 10-year study period, 55 patients underwent IAP construction for ulcerative colitis (36) and familial adenomatous polyposis (19). We assessed complications by chart review and surveyed patients regarding quality of life via a standardized questionnaire. There was no operative mortality, and there were three late deaths (6%). Twenty-nine patients (54%) sustained 68 early and late complications. Pouchitis was the most common complication (24%), and two patients required pouch excision (4%), one for pouchitis and one for rectovaginal fistula. Thirty-one patients (65%) have completed questionnaires. Forty-seven patients (87%) responded that their overall quality of life is "always" better since creation of the IAP, and only one patient in the IAP group has greater than ten bowel movements a day. Twenty-one patients (68%) never have interference with intimate relationships and 20 (65%) never have interference with physical activities. However, 20 patients (65%) sometimes have sleep interference, and 19 patients (61%) sometimes have fecal soilage. None of the patients continue to take steroids. We conclude that the complication rate following IAP construction is high, but pouch loss is infrequent. Despite a high complication rate, the majority of patients experience an improvement in quality of life.

Differential gene expression in wild-type and arnt-defective mouse hepatoma (Hepa1c1c7) cells.

The aryl hydrocarbon nuclear translocator (Arnt) is a basic helix-loop-helix (per/Arnt/Ahr/sim) PAS-containing protein that can heterodimerize with the aryl hydrocarbon receptor (AhR), the hypoxia-inducible factor-1 alpha, and other PAS-containing proteins to form transcriptionally active complexes. To identify the genes whose expression is modulated by Arnt, we used the technique of differential display to compare the expression of genes in wild-type and Arnt-defective (BPRc1) mouse hepatoma (Hepa1c1c7) cells. Here we report two gene products whose expression was reduced in BPRc1 cells (a WW domain-binding, protein-like factor and one unknown gene product) when compared to wild-type cells, and two that were elevated (Steel factor and a serpin-like protein). Comparison of the relative expression of these gene products between two independently-derived, Arnt-defective cell lines, as well as in BPRc1 cells in which Arnt expression was restored by a stably integrated Arnt-expression plasmid, revealed that each gene was expressed in an Arnt-independent manner. Our results clearly demonstrate that gene expression in the variant cell clones is distinctly different from that of the parental wild-type Hepa1c1c7 cells from which they were derived and involves genes in addition to, and unrelated to, that of Arnt. The identification of these differentially expressed gene products suggests that caution should be exercised when using these variant cell lines to confirm the role of the AhR/Arnt-signaling pathway in a given cellular response.

Activation of the Ah receptor by tryptophan and tryptophan metabolites.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of a variety of hydrophobic natural and synthetic chemicals, including the environmental contaminant 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin). A variety of indole-containing chemicals, such as indole-3-carbinol, indolo[3, 2-b]carbazole, and UV photoproducts of tryptophan (TRP), have previously been identified as ligands for AhR. Here we have examined the ability of endogenous metabolites of tryptophan (TRP) to bind to and activate AhR in vitro and in cells in culture. Although hydroxylated TRP metabolites were inactive, two metabolites, namely tryptamine (TA) and indole acetic acid (IAA), were shown to be AhR agonists. Not only do TA and IAA bind competitively to AhR, but they also can stimulate AhR transformation and DNA binding and induce expression of an AhR-dependent reporter gene in cells. In addition to being an AhR ligand, TA is also a competitive substrate for cytochrome P4501A1, a well-characterized AhR- and TCDD-inducible gene product. Although these compounds are relatively weak ligands, compared to TCDD, they represent some of the first endogenous hydrophilic AhR agonists identified to date.

Soft-tissue coverage of the neural elements after myelomeningocele repair.

We retrospectively reviewed all newborns with a diagnosis of myelomeningocele (MMC) admitted to our hospital between January 1990 and September 1994 to determine methods of soft tissue coverage, complication rates, and results. Sixty-five patients underwent repair of thoracic, lumbar, or sacral MMCs. The average size of defect repaired measured 21.3 cm2 (range, 2-80 cm2). Methods of repair included direct approximation of soft tissues with or without undermining (N = 48), Romberg Limberg flaps (N = 8), gluteus maximus or latissimus dorsi musculocutaneous flaps (N = 5), fascioutaneous flaps (N = 3), and V-gamma advancement (N = 1). A total of 18 complications were recorded (27.7%). There were 5 major complications (7.7%) and 13 minor ones (20.0%). Major complications were defined as midline wound dehiscence overlying the neural elements or wound infection leading to meningitis or ventriculitis. All 5 major and 9 minor complications arose in patients undergoing direct soft-tissue approximation. Additionally, all major complications were recorded in defects > 18 cm2. Based on this series, it appears that MMC defects < 18 cm2 can be closed by direct approximation of soft tissues without significant risk or major wound complication. Larger wounds may be successfully closed in this manner, but the risk of major complication is substantial.

Recovery from laparoscopic cholecystectomy procedures.

The authors studied the postoperative experiences of 53 patients who had uncomplicated laparoscopic cholecystectomy procedures. Patients rated their pain, nausea, vomiting, and fatigue before surgery, before discharge, and on postoperative days one, two, three, four, and seven. The majority of patients reported more difficult and painful and slower recoveries than they expected or that they believed were indicated in the education materials provided to prepare them for surgery. The experiences of the patients in this study clearly indicate a need to modify preoperative preparatory education materials.

Primary structure of four allatostatins: neuropeptide inhibitors of juvenile hormone synthesis.

Four neuropeptides that inhibit juvenile hormone synthesis by the corpora allata have been isolated from brains of the virgin female cockroach Diploptera punctata. These allatostatins are 8-13 amino acids long, are amidated, and show sequence similarity, including a 3-amino acid sequence at the C-terminal end that is common to all four peptides. The peptide sequences are as follows: allatostatin 1, Ala-Pro-Ser-Gly-Ala-Gln-Arg-Leu-Tyr-Gly-Phe-Gly-Leu-NH2; allatostatin 2, Gly-Asp-Gly-Arg-Leu-Tyr-Ala-Phe-Gly-Leu-NH2; allatostatin 3, Gly-Gly-Ser-Leu-Tyr-Ser-Phe-Gly-Leu-NH2; and allatostatin 4, Asp-Arg-Leu-Tyr-Ser-Phe-Gly-Leu-NH2. An in vitro bioassay of the synthesized allatostatins showed greater than 40% inhibition of juvenile hormone synthesis by corpora allata of virgin females with 10(-9) M allatostatin 1, 10(-8) M allatostatins 2 and 4, and 7 X 10(-7) M allatostatin 3. Inhibition by allatostatins 1-4 was reversible. In addition, allatostatin 1 inhibited juvenile hormone synthesis by corpora allata from mated females and last-instar larvae of D. punctata and corpora allata of adult female Periplaneta americana.

Telling the diagnosis of cancer.

Although a concensus has emerged in this country that patients should be told when cancer is discovered, no data is available to indicate how and where patients are currently told that they have cancer. Fifty-five patients undergoing anticancer therapy were therefore interviewed to learn how this process occurs. The majority of patients were told by surgeons (74%) and only a minority by primary care physicians (11%). Most were told in a traditional medical setting (42% in the doctor's office, 17% in a hospital room), but 23% were told over the telephone and 19% in the recovery room. Two indicators of patient satisfaction with the telling process suggested that different sites of telling were not equivalent. Patients told over the telephone or in the recovery room were more likely to describe the telling in negative terms and less likely to describe their doctors as being helpful in understanding their illness than those told in a doctor's office or in their hospital bed. This pilot study indicates considerable variation in this aspect of patient care and suggests directions for future research. To determine whether interviews that explore these issues with cancer patients are unpleasant or stressful, patients' reactions to being subjects in this study were sought. Patients asked directly at the completion of the interview or surveyed 2 to 4 months later said the interview had been helpful and/or a positive experience. None expressed negative feelings about participating. Concerns about the psychological harm resulting from such study of this patient group do not appear to be warranted and should not impede future research.