Histopathological Evaluation Of Tissues Research Articles

Protoporphyrin IX in serum of high-grade glioma patients: A novel target for disease monitoring via liquid biopsy.

High-grade gliomas (HGG) carry a dismal prognosis. Diagnosis comprises MRI followed by histopathological evaluation of tissue; no blood biomarker is available. Patients are subjected to serial MRIs and, if unclear,surgery for monitoring of tumor recurrence, which is laborious. MRI provides only limited diagnostic information regarding the differentiation of true tumor progression from therapy-associated side effects. 5-aminolevulinic acid (5-ALA)is routinely used for induction of protoporphyrin IX (PpIX) accumulation in malignant glioma tissue, enablingimproved tumor visualizationduring fluorescence-guided resection (FGR). We investigated whether PpIX can also serve as a serum HGG marker to monitor relapse. Patients (HGG: n = 23 primary, pHGG; n = 5 recurrent, rHGG) undergoing FGR received 5-ALA following standard clinical procedure. The control group of eight healthy volunteers (HCTR) also received 5-ALA. Serum was collected before and repeatedly up to 72h after drug administration. Significant PpIX accumulation in HGG was observed after 5-ALA administration (ANOVA: p = 0.005, post-hoc: HCTR vs. pHGG p = 0.029, HCTR vs. rHGG p = 0.006). Separation of HCTR from pHGG was possible when maximum serum PpIX levels were reached (CI95% of tMax). ROC analysis of serum PpIX within CI95% of tMax showed successful classification of HCTR and pHGG (AUCROC 0.943, CI95% 0.884-1.000, p < 0.001); the optimal cut-off for diagnosis was 1275pmolPpIX/ml serum, reaching 87.0% accuracy, 90.5% positive predictive and 84.0% negative predictive value. Baseline PpIX level was similar in patient and control groups. Thus, 5-ALA is required for PpIX induction, which is safe at the standard clinical dosage. PpIX is a new target for liquid biopsy in glioma. More extensive clinical studies are required to characterize its full potential.

A Rare Case Report of Idiopathic Infected Radicular Cyst

Peri radicular pathosis can be differentially diagnosed as odontogenic or non-odontogenic cyst, epithelial cyst, neoplastic lesions or non-neoplastic bone lesions and inflammatory lesions. But diagnosis can only be made on the basis of clinical, radiographic features, histopathological evaluation of tissues and cytological evaluation of fluid. In this case report teeth were non vital with radicular cystic lesion size &gt; 10mm. Histological examination revealed presence of cholesterol clefts, foam and giant cells. Enucleation in combination with root canal treatment, GBR with xenograft and membrane helps to get the predictable outcome.

Developing a Prenatal Acute Exposure and Medical Countermeasure Evaluation Model for Organophosphate Compounds in a Genetically Modified Mouse

Organophosphate (OPs) compounds make up the most common class of pesticides as well as chemical warfare nerve agents (CWNA), all of which covalently inhibit the active site of acetylcholinesterase (AChE), resulting in intoxication via a cholinergic crisis. While the biochemical mechanism of action resulting in acute intoxication of an exposed individual is well understood, less is known about the mechanism of OP intoxication via other exposure routes, particularly prenatal exposure. The clinical effects of non‐acute prenatal OP exposure have been previously studied primarily in cases involving diet and agricultural labor, while case studies documenting the effects on conception of acute exposure during chemical warfare attacks (Japan 1995, Syria 2013 and 2017) have also been published. Such exposure events were linked to a range of serious neurodevelopmental anomalies in children, but the underlying mechanism of action as well as the potential benefits of medical countermeasures have not been clearly elucidated. A robust human‐relevant animal model to test both is therefore essential for evaluating current and future OP countermeasures. The present study used a novel humanized mouse strain expressing human AChE and an inactivated native serum carboxylesterase to create a prenatal acute exposure and emergency medical countermeasure evaluation model. Pregnant mice were acutely exposed to an OP at a critical point in cholinergic development, generally equivalent to the first trimester in humans. Dams were challenged with either sarin or the pesticide paraoxon, followed by either a saline vehicle control or 2‐PAM and an atropine/midazolam cocktail, the currently fielded emergency treatment for OP intoxication. Mice were allowed to carry pups to term, and upon reaching maturity, cortex, cerebellum, bone marrow and gonads were collected from offspring in each exposure group. Phenotypical and histopathological evaluation of tissues and other factors in dams and offspring were evaluated. Gene expression analyses conducted for each tissue generated a detailed profile associated with each OP exposure/treatment group, providing robust criteria for model development. The resulting data demonstrated a significant beneficial impact of medical countermeasures for both sarin and paraoxon exposures, significantly reducing the amount and the scope of gene expression changes induced by OP exposure. This model provides insight into the developmental pathologies resulting from prenatal acute OP exposure as well as serves as an evaluation model for future treatments.

Preoperative Differentiation of Uterine Leiomyomas and Leiomyosarcomas: Current Possibilities and Future Directions.

Simple SummaryUterine sarcomas are the second most common unexpected malignancy diagnosed after surgery. It is worrisome, as its preoperative diagnosing can impact the choice of the treatment method, including surgery. Therefore, nowadays, many researchers are trying to find innovative methods to differentiate benign and malignant lesions of the uterus preoperatively. The review of the current literature showed that the use of more than one parameter in specific diagnostic scales is one of the most effective methods. Moreover, machine learning models and artificial intelligence (AI) are hope-giving directions, which may help in preoperative ULMS and ULM distinguishment. In order to collect a large amount of ULMS patients, multicenter databases seem necessary.The distinguishing of uterine leiomyosarcomas (ULMS) and uterine leiomyomas (ULM) before the operation and histopathological evaluation of tissue is one of the current challenges for clinicians and researchers. Recently, a few new and innovative methods have been developed. However, researchers are trying to create different scales analyzing available parameters and to combine them with imaging methods with the aim of ULMs and ULM preoperative differentiation ULMs and ULM. Moreover, it has been observed that the technology, meaning machine learning models and artificial intelligence (AI), is entering the world of medicine, including gynecology. Therefore, we can predict the diagnosis not only through symptoms, laboratory tests or imaging methods, but also, we can base it on AI. What is the best option to differentiate ULM and ULMS preoperatively? In our review, we focus on the possible methods to diagnose uterine lesions effectively, including clinical signs and symptoms, laboratory tests, imaging methods, molecular aspects, available scales, and AI. In addition, considering costs and availability, we list the most promising methods to be implemented and investigated on a larger scale.

Discovery of a Novel Potent and Selective Calcium Release-Activated Calcium Channel Inhibitor: 2,6-Difluoro-N-(2'-methyl-3'-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-[1,1'-biphenyl]-4-yl)benzamide. Structure-Activity Relationship and Preclinical Characterization.

The role of calcium release-activated calcium (CRAC) channels is well characterized and is of particular importance in T-cell function. CRAC channels are involved in the pathogenesis of several autoimmune diseases, making it an attractive therapeutic target for treating inflammatory diseases, like rheumatoid arthritis (RA). A systematic structure-activity relationship study with the goal of optimizing lipophilicity successfully yielded two lead compounds, 36 and 37. Both compounds showed decent potency and selectivity and a remarkable pharmacokinetic profile. Further characterization in in vivo RA models and subsequent histopathological evaluation of tissues led to the identification of 36 as a clinical candidate. Compound 36 displayed an excellent safety profile and had a sufficient safety margin to qualify it for use in human testing. Oral administration of 36 in Phase 1 clinical study in healthy volunteers established favorable safety, tolerability, and good target engagement as measured by levels of IL-2 and TNF-α.

A Whole Virion Vaccine for COVID-19 Produced via a Novel Inactivation Method and Preliminary Demonstration of Efficacy in an Animal Challenge Model

The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAX) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this preliminary evaluation provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results of this preliminary evaluation suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have potential utility in the preparation of one such vaccine candidate.

Usability of donor corneas harvested from the deceased having septicaemia or malignancy.

There is a wide gap between supply and demand in relation to healthy corneal grafts. Specific contraindications like infection and malignancy lead to non-usage of many grafts, despite the fact that deeming graft unhealthyness for these two contraindications is debatable. This study was conceptualized to assess if corneas donated from the deceased with septicaemia or malignancy can be deemed fit for implantation. Retrospective histopathological and microbiological analysis of cadaveric donor corneas. A total of 76 donor corneas from 38 patients rejected for corneal transplantation in view of patient having septicaemia or malignancy were analysed for pathological and microbiological workup, to look for dissemination of disease within corneal tissue. Pathology workup included gross and microscopic histopathological evaluation of tissue. Microbiology workup included Grams stain and KOH with calcofluor mount, culture in blood agar, chocolate agar, Sabourauds dextrose agar and Mc Conkeys broth. A total of 46 donor corneas of 23 septicaemia patients when evaluated showed presence of culture positive infection in 18 patients (78.2%). Histopathological examination done for 30 donor corneas from 15 cancer patients did not reveal presence of tumour cells in the specimen. Corneas of two of cancer patients having septicaemia revealed growth on cultures. Corneal tissues harvested from septicaemia donors showed significantly higher incidence of corneal contamination, confirming their unsuitability for usage. However, there was no incidence of tumour transmission in corneal tissues of the patients with malignancies, suggesting that they can be considered for ophthalmic purpose.

Fourier transform infrared spectroscopic imaging of wear and corrosion products within joint capsule tissue from total hip replacements patients.

Implant debris generated by wear and corrosion is a prominent cause of joint replacement failure. This study utilized Fourier transform infrared spectroscopic imaging (FTIR-I) to gain a better understanding of the chemical structure of implant debris and its impact on the surrounding biological environment. Therefore, retrieved joint capsule tissue from five total hip replacement patients was analyzed. All five cases presented different implant designs and histopathological patterns. All tissue samples were formalin-fixed and paraffin-embedded. Unstained, 5 μm thick sections were prepared. The unstained sections were placed on BaF2 windows and deparaffinized with xylene prior to analysis. FTIR-I data were collected at a spectral resolution of 4 cm-1 using an Agilent Cary 670 spectrometer coupled with Cary 620 FTIR microscope. The results of study demonstrated that FTIR-I is a powerful tool that can be used complimentary to the existing histopathological evaluation of tissue. FTIR-I was able to distinguish areas with different cell types (macrophages, lymphocytes). Small, but distinct differences could be detected depending on the state of cells (viable, necrotic) and depending on what type of debris was present (polyethylene [PE], suture material, and metal oxides). Although, metal oxides were mainly below the measurable range of FTIR-I, the infrared spectra of tissues exhibited noticeable difference in their presence. Tens of micrometer sized polyethylene particles could be easily imaged, but also accumulations of submicron particles could be detected within macrophages. FTIR-I was also able to distinguish between PE debris, and other birefringent materials such as suture. Chromium-phosphate particles originating from corrosion processes within modular taper junctions of hip implants could be identified and easily distinguished from other phosphorous materials such as bone. In conclusion, this study successfully demonstrated that FTIR-I is a useful tool that can image and determine the biochemical information of retrieved tissue samples over tens of square millimeters in a completely label free, nondestructive, and objective manner. The resulting chemical images provide a deeper understanding of the chemical nature of implant debris and their impact on chemical changes of the tissue within which they are embedded.

Effectiveness of Methylene Blue in the Prevention of Stifle Joint Arthrofibrosis in Rabbit Models.

One of the major challenges in orthopedic surgery is the prevention of arthrofibrosis, which can be successfully alleviated in its early stages. Many studies suggest the administration of methylene blue (MB) as an accessible and effective agent for the prevention of post-operation adhesions. The purpose of this study was to evaluate the efficacy of MB in the prevention of arthrofibrosis. This study was conducted on 18 New Zealand white female mature rabbits. The anterior cruciate ligament of the left stifle joint of each animal was cut during aseptic surgery. In the next step, the rabbits were divided into three groups based on their treatments. The rabbits in the first, second, and third groups were subjected to the injection of normal saline, 1% MB solution, and 2% MB solution into their synovial space, respectively. The postoperative stifle range of motion was measured every week. After 4 weeks, the animals were euthanized and all joints were dissected for histopathology. The histopathological evaluation of tissues indicated the presence of fibrotic connective tissue as a sign of fibrosis in all groups. The fibrosis rate, inflammatory rate, tissue disarrangement, fibroblastic cellularity, and granulation tissue formation were at their highest levels in the 1% MB group. The integrity of articular cartilage in the 2% MB group was lower than the other groups. The level of bone degeneration was similar in both MB groups; however, it was more than the control saline group. The range of motion was reduced during the first week, then increased in the second and third weeks, and finally decreased in the fourth week. The MB was not an effective method regarding the prevention or treatment of arthofibrosis and the subsequent osteoarthritis. In contrast with previous studies, fibrosis was lower in the high dose MB group, compared to the low dose MB group. The alterations in the range of motion were related to the reduced movement caused by the pain and stiffness of the operated joints. The current study can be considered as the first report addressing the adverse effect of MB on synovial components. I.

Role of tissue eosinophils in chronic rhinosinusitis-associated olfactory loss.

Olfactory dysfunction is 1 of the hallmark symptoms of chronic rhinosinusitis (CRS). Eosinophilic inflammation has been implicated as a potential causative factor. However, prior studies have been limited by retrospective study designs, concomitant use of systemic corticosteroids, and other confounding factors. CRS and healthy non-CRS control subjects undergoing endoscopic sinus or skull-base surgery were prospectively enrolled and completed olfactory testing utilizing the 40-item Smell Identification Test (SIT) immediately prior to surgery. Histopathological evaluation of tissue excised from the ethmoid bulla was performed by a pathologist in a blinded fashion. Disease severity and patient-reported outcomes were measured via the Lund-Mackay computed tomography (CT) grading system and 22-item Sino-Nasal Outcome Test (SNOT-22), respectively. The associations between olfactory function, tissue eosinophilia, and disease severity were analyzed using Spearman rank order correlation and multiple linear regression. Twenty-seven (27) subjects with CRS without nasal polyps (CRSsNP), 32 subjects with CRS with nasal polyps (CRSwNP), and 10 healthy non-CRS controls were enrolled. CRSwNP was associated with higher mean tissue eosinophil counts (71.6 vs 28.1 eosinophils/high-power field [HPF], p < 0.05) and lower age/sex-adjusted SIT scores (-17.4 vs -6.2, p < 0.001) when compared to CRSsNP. SIT scores were strongly negatively correlated with tissue eosinophil counts in CRSwNP (r = -0.60, p = 0.0003), but not CRSsNP (r = 0.16, p = 0.42). The correlation between olfactory function and tissue eosinophilia in CRSwNP persisted after adjusting for disease severity. Tissue eosinophilia is associated with olfactory loss in CRSwNP, independent of disease severity. These results suggest a possible role for eosinophils or eosinophil-associated cytokines in CRS-associated olfactory loss.

Could mucin 16 and colony-stimulating factor 2-receptor beta possible graft versus host disease biomarkers? Medical hypotheses

Graft versus host disease (GVHD) occurs after bone marrow transplantation and is one of the most important causes of death worldwide. Reviews demonstrated GVHD patients with involvement of various tissues and organs, such as salivary glands. The diagnosis of acute GVHD has been the biopsies and the histopathologic evaluation of tissue from an involved organ. These procedures are invasive. Saliva proteins as possible biomarker for GVHD could facilitate the management and diagnosis accuracy. For support the proposed hypotheses, in this pilot study we collected whole saliva samples from patients with undergoing allogeneic hematopoietic cell transplantation (HCT) and from healthy subjects. Samples were collected prospectively between pre-transplant, thirty days, one hundred and, two hundred days after transplant. The proteomic profile was analyzed using SDS-PAGE and LCMS–ESI–IT-TOF mass spectrometry. The relevant personal data, past medical history were also recorded. The most relevant proteins found exclusively in GVHD patients were: CSF2RB, Protocadherin (Pcdh) Fat 2 precursor, protein capicua homolog isoform CIC-S, MUC16 and RGPD8_HUMAN RANBP2. This study aims to conduct an initial evaluation of the possible presence of such biomarkers in saliva from GVHD patients, and suggested a potential application of proteomics analysis as a alternative method to diagnose GVHD.

Histopathological evaluation of tissue undergoing thermal insult

Context:Thermal insult is the major cause of thermal injury or death and in case of death due to thermal injury the body often has to be recovered from the site. Histologically, one can predict whether the victim was alive or dead when the fire was on going. However, determination of probable cause of thermal insult to which victim subjected to be difficult when the victim's body is found somewhere else from the crime scene or accident site or found alone. Hence, histopathological evaluation of the tissue which has undergone thermal insult in such conditions could help to place evidence in front of law officials, regarding probable condition, or scenario at time of burn of victim.Aims:Keeping this as a criteria in this study we aim to evaluate burnt tissue histopathologically, that undergone various degree of thermal insult, which simulates various real life scenario for mortality in burn cases.Settings and Design:We evaluate the changes in hematoxylin and eosin staining pattern of tissue which has undergone thermal insult compared to normal tissue and also the progressive changes in staining pattern, architectural, and cellular details.Materials and Methods:Samples were taken from the patients, in various surgical procedures. Each sample was cut into five parts with close margins so that each burnt tissue is evaluated for same field or region. The tissue that obtained was immediately subjected to varying degree of temperature over a specific period so as to simulate the various real-life condition. Then the tissues were fixed, processed, and stained with routine H and E staining. The processed slides of tissue were examined under the microscope, and the staining, and architectural changes were evaluated and described.Results:Results show that there was a progressive changes in the architectural pattern of the epithelium and connective tissue showing cleft formation and vacuolization, staining pattern also shows mixing of stains progressively as the severity of thermal insult increases.

Is routine pathological evaluation of tissue from gynecomastia necessary? A 15-year retrospective pathological and literature review

Objective To reconsider the routine plastic surgical practice of requesting histopathological evaluation of tissue from gynecomastia. Method The present study was a retrospective histopathological review (15-year period [1996 to 2012]) involving gynecomastia tissue samples received at the pathology laboratory in the Saskatoon Health Region (Saskatchewan). The Laboratory Information System (LIS) identified all specimens using the key search words “gynecomastia”, “gynaecomastia”, “gynecomazia” and “gynaecomazia”. A literature review to identify all cases of incidentally discovered malignancies in gynecomastia tissue specimens over a 15-year period (1996 to present) was undertaken. Results The 15-year LIS search detected a total of 452 patients that included two cases of pseudogynecomastia (0.4%). Patients' age ranged from five to 92 years and 43% of the cases were bilateral (28% left sided, 29% right sided). The weight of the specimens received ranged from 0.2 g to 1147.2 g. All cases showed no significant histopathological concerns. The number of tissue blocks sampled ranged from one to 42, averaging four blocks/case (approximately $105/case), resulting in a cost of approximately $3,200/year, with a 15-year expenditure of approximately $48,000. The literature review identified a total of 15 incidental findings: ductal carcinoma in situ (12 cases), atypical ductal hyperplasia (two cases) and infiltrating ductal carcinoma (one case). Conclusions In the context of evidence-based literature, and because no significant pathological findings were detected in this particular cohort of 452 cases with 2178 slides, the authors believe it is time to re-evaluate whether routine histopathological examination of tissue from gynecomastia remains necessary. The current climate of health care budget fiscal restraints warrants reassessment of the current policies and practices of sending tissue samples of gynecomastia incurring negative productivity costs on routine histopathological examination.

Expressions of TRPM6 and TRPM7 and histopathological evaluation of tissues in ischemia reperfusion performed rats

There is very little work on the expression of TRPM6/7 in ischemia reperfusion models. In previous studies, after ischemia, reperfusion had been kept limited to 24 h, yet in our study, expressions of these channels were elucidated after its modification to 48 h to establish what kind of changes renal tissues undergo. For the current study, 20 Wistar albino rats were divided into two groups equally. Group I: control group, Group II = I/R group (60 min ischemia + 48 h reperfusion). For the mRNA analysis, right kidneys of I/R group was used as a reference in order to eliminate genetic differences. The left renal artery (I/R generated part) of I/R area was removed from all rats in the second group. Likewise, normal tissues of right renal artery were removed from all rats. Histopathologic scoring of the tissue samples were achieved semi-quantitatively according to normal tissue composition. Consequently, both TRPM6 and TRPM7 expression levels were decreased in all groups according to control groups, yet results were not counted as significant (p > 0.05). Additionally, correlation analysis confirmed these results. Also, I/R performed kidneys had more tissue damage compared to control group. To conclude, our study results suggest that TRPM6/7 expressions may be increased and after 48 h of reperfusion expression levels of these two stored to normal levels. At the same time, damages have occurred in renal tissues after ischemia. These damages were considered to be resulted from the oxidative effects as previously reported.

Is routine pathological evaluation of tissue from gynecomastia necessary? A 15-year retrospective pathological and literature review

To reconsider the routine plastic surgical practice of requesting histopathological evaluation of tissue from gynecomastia. The present study was a retrospective histopathological review (15-year period [1996 to 2012]) involving gynecomastia tissue samples received at the pathology laboratory in the Saskatoon Health Region (Saskatchewan). The Laboratory Information System (LIS) identified all specimens using the key search words "gynecomastia", "gynaecomastia", "gynecomazia" and "gynaecomazia". A literature review to identify all cases of incidentally discovered malignancies in gynecomastia tissue specimens over a 15-year period (1996 to present) was undertaken. The 15-year LIS search detected a total of 452 patients that included two cases of pseudogynecomastia (0.4%). Patients' age ranged from five to 92 years and 43% of the cases were bilateral (28% left sided, 29% right sided). The weight of the specimens received ranged from 0.2 g to 1147.2 g. All cases showed no significant histopathological concerns. The number of tissue blocks sampled ranged from one to 42, averaging four blocks/case (approximately $105/case), resulting in a cost of approximately $3,200/year, with a 15-year expenditure of approximately $48,000. The literature review identified a total of 15 incidental findings: ductal carcinoma in situ (12 cases), atypical ductal hyperplasia (two cases) and infiltrating ductal carcinoma (one case). In the context of evidence-based literature, and because no significant pathological findings were detected in this particular cohort of 452 cases with 2178 slides, the authors believe it is time to re-evaluate whether routine histopathological examination of tissue from gynecomastia remains necessary. The current climate of health care budget fiscal restraints warrants reassessment of the current policies and practices of sending tissue samples of gynecomastia incurring negative productivity costs on routine histopathological examination.

Bioavailability enhancement of ondansetron after nasal administration of Caesalpinia pulcherrima-based microspheres

Context: Natural polymers have attracted a great deal of attention for use as potential carriers in site-specific delivery over past decades. Mucoadhesive microspheres are useful tools for nasal drug delivery. Objectives: To prepare and evaluate mucoadhesive microspheres as mode for nasal delivery of ondansetron using Caesalpinia pulcherrima galactomannan (CPG). Materials and methods: Conventional spray-dried CPG nasal microspheres loaded with ondansetron for intranasal drug delivery in order to avoid the first pass metabolism with improved therapeutic efficiency in treatment of nausea and vomiting as an alternative therapy to parenterals. Developed microspheres were evaluated for characteristics like particle size, entrapment efficiency, zeta potential, swelling ability, in-vitro mucoadhesion, in-vitro drug release, DSC, XRD study and histopathological evaluation of tissue. CPG-based ondansetron microspheres were studied in rabbits for screening nasal absorption potential of nasal formulation. Results: Developed nasal microspheres possess entrapment efficiency of 80–89%, higher mucoadhesion of 72–84% across goat nasal mucosa. In-vivo study showed that microspheres based on mucoadhesive polymer were able to promote quick drug absorption as well as enhanced bioavailability of drug. Discussion: Histopathological studies evaluated biocompatible and nontoxic nature of CPG in nasal cavity. Developed mucoadhesive microspheres by nasal route showed enhancement of bioavailability as compared to oral route in rabbits. Conclusion: CPG-based mucoadhesive microspheres can successfully deliver ondansetron intranasally, sustain its effect, avoid first pass effect, an alternative route of administration to injection and thus enhance systemic bioavailability of ondansetron hydrochloride.

Tu1642 Inhibition of mTOR Mediates Alleviation of Intestinal Fibrosis via Suppression of Myofibroblast Proliferation

a porcine model of stress-induced gut injury. Nine-week-old pigs that were previously subjected to early weaning stress, co-mingled with unfamiliar (non-littermate) pigs to induce social stress. Six-hours following social stress, animals were treated daily with either lubiprostone (μ0.3μg/ kg) or placebo once daily gavage PO for 3-days. Following the treatment period, colonic tissues were harvested and mounted in Ussing chambers. The transepithelial electrical resistance (TER) in the colon of stressed pigs was found to be reduced by 30% compared to control non-stressed pig colon (p,0.01). Stressed pigs treated with lubiprostone showed significantly increased TER compared to placebo treated stressed pigs. Consistent with the changes in TER, stressed placebo-treated pigs had increased paracellular flux of 3H-mannitol, and treatment with lubiprostone prevented the increase in paracellular flux of mannitol caused by stress. Initial histopathological evaluation of tissues revealed no differences between groups in epithelial appearance, which appeared normal and continuous. However, further evaluation of the mucosa and sub mucosa is required. Thus, data demonstrate a beneficial influence of lubiprostone on intestinal barrier properties in a porcine model of psychosocial stress. * (Amitiza) -R-Tech-Ueno, Tokyo, Japan

Cystic Endometrial Hyperplasia and Pyometra in Three Captive African Hunting Dogs (Lycaon pictus)

Pyometra and cystic endometrial hyperplasia are common in domestic canids and are suspected to develop as a consequence of elevated progesterone levels. Reports of uterine pathology in exotic canids are limited, with some speculating of association with contraception. This report describes pyometra, cystic endometrial hyperplasia, and ovariohysterectomy in three African hunting dogs (Lycaon pictus). Ovarian corpora lutea were detected in two of the dogs, suggesting endogenous progesterone production. One dog had a uterine adenocarcinoma and two had ovarian granulosa cell tumors. Clinical signs included anorexia, lethargy, vulvar discharge, polyuria, polydipsia, and abdominal distention. Diagnosis was based on clinical signs, physical examination, bloodwork, radiography, and ultrasonography, with confirmation through histopathologic evaluation of tissues. Cystic endometrial hyperplasia, pyometra, and uterine neoplasia have rarely been diagnosed in exotic canids; however, they should be considered as differential diagnoses in intact bitches that present with suspected reproductive disease.

Sporotrichosis: a retrospective evaluation of 23 cases seen in northern California (1987–2007)

Sporotrichosis is an uncommon to rare cutaneous and subcutaneous mycosis of animals and humans caused by the dimorphic fungus Sporothrix schenckii. Twenty-three mammalian cases of sporotrichosis examined between 1987 and 2007 at the University of California, Davis - Veterinary Medical Teaching Hospital, were retrospectively evaluated with regard to the historical, clinical, diagnostic and treatment findings. Cats were the most common species affected (n = 14). In addition, sporotrichosis was diagnosed in four dogs, four horses and a donkey. Six of 23 cases were diagnosed with the localized cutaneous form of sporotrichosis (four cats, one dog, one horse), 10 with the cutaneous-lymphatic form (four cats, two dogs, three horses and a donkey), and seven with the disseminated form (six cats, one dog). Two of 23 cases did not have skin lesions at the time of diagnosis (one cat, one dog). The most common mode of diagnosis was demonstration of S. schenckii on histopathological evaluation of tissue. In contrast with most previously described sporotrichosis infections in cats, few to no fungal organisms were seen in histopathological samples (haematoxylin and eosin and special stains) in five of the 14 cats. Treatments received included itraconazole (12 cats, one dog), ketoconazole (three dogs), fluconazole (one cat, one donkey), sodium iodide (four horses, one cat) and potassium iodide (one cat, one horse, one donkey). The prognosis for successful treatment was good in all species. Fluconazole was successful in inducing resolution of the cutaneous lesions and controlling the infection in one cat with disseminated sporotrichosis.

Changes in the spleen and liver of pregnant sows and full-term piglets after feeding diets naturally contaminated with deoxynivalenol and zearalenone

Wheat contaminated naturally with the Fusarium toxins deoxynivalenol (DON) and zearalenone (ZON) was fed to pregnant Landrace sows for 35 days. On day 110, caesarean section was carried out, the offspring were killed immediately after birth, and their livers and spleens examined. At necropsy there were no macroscopic lesions observed in any organ of either sows or piglets. Histopathological evaluation of tissues from sows of the treated group revealed changes in liver and spleen tissues, whereas no significant changes were observed in these tissues in their piglets. Liver damage, as measured by prominent elevated transaminase activities, was not detected in the serum of the sows. In pregnant sows there were individual variations in sensitivity to the Fusarium toxins. In conclusion, it can be assumed that there are no adverse effects on the liver and spleen of full-term piglets when their mothers consumed diets containing up to 9570 and 358 μg DON/ZON per kg diet.