Multiple pituitary hormone deficiencies in a kitten: Hyposomatotropism, hypothyroidism, central diabetes insipidus and hypogonadism.

In humans, post-traumatic hypopituitarism (PTHP) is a common complication of traumatic brain injury, with the most frequently reported hormonal deficiencies resulting in hyposomatotropism and hypogonadism, followed by hypothyroidism, hypocortisolism, and central diabetes insipidus. To date, PTHP has rarely been reported in cats, and the reported cases often describe a single hormone deficiency. This report details an approximately 7-month-old cat with a history of suspected traumatic brain injury at 5 wk of age, that presented with growth retardation (1.53 kg) and polyuria-polydipsia. Thyroid panel, thyrotropin-releasing hormone stimulation test, thyroid scan with Technetium-99, repeat measurement of serum IGF-1, resting cortisol, endogenous ACTH concentration, and ACTH stimulation testing were performed. The cat was diagnosed with presumptive PTHP leading to hyposomatotropism, hypothyroidism, central diabetes insipidus, and hypogonadism. In this case, treatment of the hypothyroidism and central diabetes insipidus were successful. Hyposomatotropism and hypogonadism were not treated. Although reported feline PTHP cases have described a single hormone deficiency, this report details a cat with presumptive PTHP leading to hyposomatotropism, hypothyroidism, central diabetes insipidus, and hypogonadism. Attention should be paid to the potential for the development of PTHP in cats secondary to traumatic brain injury. Key clinical message: Post-traumatic hypopituitarism in cats can lead to multiple hormone deficiencies, leading to hyposomatotropism, hypothyroidism, central diabetes insipidus, and hypogonadism.

Insuffisances hormonales hypophysaires multiples chez un chaton : hyposomatotropisme, hypothyroïdie, diabète insipide central et hypogonadisme. En médecine humaine, l'hypopituitarisme post-traumatisme crânien (HPPT) est une complication fréquente après un trauma crânien. Les insuffisances hormonales les plus fréquemment rapportées sont l'hyposomatotropisme et l'hypogonadisme, suivis de l'hypothyroïdie, de l'hypocortisolisme et du diabète insipide central. À ce jour, l'HPPT a rarement été décrit chez le chat, et les cas publiés décrivent bien souvent une déficience hormonale unique. Dans le cas présent, un chat âgé d'environ 7 mois, avec un antécédent de trauma crânien suspecté à l'âge de 5 semaines, a été présenté avec un retard de croissance (1,53 kg) et un syndrome polyurie-polydipsique. Les examens d'endocrinologie complémentaires incluaient le dosage des hormones thyroïdiennes, la stimulation de l'hypophyse par la thyrolibérine, une scintigraphie thyroïdienne (Technetium-99), le dosage de l'IGF-1, du cortisol basal, de la concentration d'ACTH endogène, et un test de stimulation à l'ACTH. Le chat a été diagnostiqué de manière présomptive avec un HPPT causant de multiples insuffisances hormonales hypophysaires : hyposomatotropisme, hypothyroïdie, diabète insipide central et hypogonadisme. Chez ce chat, le traitement de l'hypothyroïdie et du diabète insipide central a été réussi. L'hyposomatotropisme et l'hypogonadisme n'ont pas été traités. Alors que les rapports de cas publiés sur l'HPPT félin décrivent souvent une seule déficience hormonale, ce chat a été diagnostiqué avec de multiples insuffisances hormonales hypophysaires. Les cliniciens doivent rester attentifs au développement potentiel d'un hypopituitarisme après un trauma crânien.Message clinique clé :L'hypopituitarisme post-traumatique chez le chat peut entraîner de multiples déficiences hormonales, entraînant un hyposomatotropisme, une hypothyroïdie, un diabète insipide central et un hypogonadisme.(Traduit par les auteurs).

Case report: Hypoadrenocorticism crisis complicated by non-cardiogenic pulmonary edema in a dog.

A 6-year-old castrated male Labradoodle was referred in uncompensated hypovolemic shock, with a 72-h history of lethargy, vomiting and diarrhea that had acutely worsened with subsequent development of profuse hemorrhagic diarrhea in the last 24 h after a visit to the groomer. In most respects this case was classic for a patient with a primary hypoadrenocortical crisis. After initial attempts to address hypovolemia and refractory hypotension, no clinical improvement was seen, and the respiratory rate had increased acutely to 80 bpm with crackles detected on thoracic auscultation and serosanguineous fluid began draining from the nose and mouth. An arterial blood gas sample while breathing room air revealed moderate hypoxemia (PaO2 59.9: RI 95-100 mmHg), an elevated alveolar-arterial (A-a) gradient at 54.7 (RI < 15 mmHg) and a PaO2:FiO2 ratio of 285 mmHg. Thoracic radiographs revealed severe bilateral alveolar lung pattern largely limited to the perihilar and caudodorsal lung fields. The radiographic findings, along with signs of ongoing hypovolemia, the lack of evidence of typical long-standing acquired cardiac disease, and the rapid resolution of the pulmonary edema without the need for diuretics or long-term cardiac medications supported non-cardiogenic pulmonary edema. The proposed cause of the non-cardiogenic pulmonary edema was speculated to be neurogenically mediated. Oxygen supplementation along with mineralocorticoid and glucocorticoid replacement therapy was sufficient for the management of the non-cardiogenic pulmonary edema in this case.

Online survey to determine client perceptions of feline chronic lower airway disease management: response to therapy, side effects and challenges encountered.

OBJECTIVES: The first aim of this survey was to report client experiences associated with the administration of common medications, particularly glucocorticoids and bronchodilators, in managing cats with feline lower airway disease (FLAD). The second aim was to ascertain client perception of response to treatment and level of satisfaction. METHODS: This was a prospective cross-sectional study. An online survey was distributed worldwide to cat owners caring for cats with a chronic cough. Only cats reported to have FLAD were included. RESULTS: A total of 153 complete responses describing cats with FLAD were analyzed. Glucocorticoids and bronchodilators were the predominantly prescribed therapeutics for 140/153 (92%) and 80/153 (52%) of FLAD cats, respectively. Oral and inhalant administration routes were reported most commonly: glucocorticoids (64% oral and 75% inhalant) and bronchodilators (21% oral and 88% inhalant). A review of how air quality could be improved was conducted for 54% of cats. Almost half (43%) of owners reported adverse effects secondary to glucocorticoid administration, the most frequent being polyphagia (26%) and polydipsia (21%). Only 10% of owners reported bronchodilator-associated side effects, with restlessness (9%) being the most common. Difficulties giving glucocorticoid or bronchodilator tablets orally were reported for 33% and 71% of owners, respectively. Glucocorticoid or bronchodilator inhalant therapies were difficult to administer for 28% and 31% of owners, respectively. Frequency and severity of coughing were significantly lower after at least 2 months of treatment, with median numerical input on a slider scale (0-100) of 48 and 42 before, and 10 and 7 after treatment, respectively (P <0.0001). Median numerical input of owner satisfaction was 83%. CONCLUSIONS AND RELEVANCE: Despite significant improvements in client-reported responses to treatment, challenges associated with the administration of medications and their adverse effects still exist. Promoting awareness of client experiences can facilitate appropriate follow-up, guidance and empathy to further optimize outcomes.

Association between hyperlipidemia and calcium oxalate lower urinary tract uroliths in dogs.

BACKGROUND: Metabolic syndrome is associated with formation of calcium oxalate (CaOx) uroliths in humans. OBJECTIVES: To investigate the association between obesity and hyperlipidemia with CaOx lower urinary tract uroliths in client-owned dogs. ANIMALS: Dogs with (n = 55, U [uroliths]-dogs) and without (n = 39, UF [uroliths-free]-dogs) CaOx lower urinary tract uroliths. METHODS: Case-control study. U-dogs were retrospectively enrolled and compared to UF-dogs. Body condition score (BCS; 1-9 scoring scale), serum triglyceride (TG) and total cholesterol (CH) concentrations and glycemia (after >12-hour food withholding) were recorded in both groups. RESULTS: On univariate logistic regression, when excluding Miniature Schnauzers, odds of having uroliths increased by a factor of 3.32 (95% CI 1.38-11.12) for each mmol/L of TG (P = .027), of 39 (95% CI 9.27-293.22) for each mmol/L of glycemia (P < .0001), and of 2.43 (95% CI 1.45-4.45) per unit of BCS (P = .002). In multivariable models, the effect of TG was retained when all breeds were included for analysis and odds of having uroliths increased by a factor of 4.34 per mmol/L of TG (95% CI 1.45-19.99; P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Serum lipid screening in dogs diagnosed with CaOx uroliths might be recommended to improve their medical staging and management.

Histopathologic, phenotypic, and molecular criteria to discriminate low-grade intestinal T-cell lymphoma in cats from lymphoplasmacytic enteritis.

BACKGROUND: Differentiation of low-grade intestinal T-cell lymphoma (LGITL) from lymphoplasmacytic enteritis (LPE) in cats is a diagnostic challenge for pathologists. OBJECTIVE: Characterize histologic, immunohistochemical, and molecular features of LGITL and LPE. ANIMALS: Forty-four client-owned cats, 22 diagnosed with LGITL and 22 with LPE. METHODS: Prospective, cohort study. Clinical suspicion of LGITL or LPE was based on persistent gastrointestinal signs, unresponsive to empirical treatments. All cats underwent a standardized diagnostic evaluation, including biopsy (preferentially full-thickness), and were diagnosed with LGITL or LPE after review of clinical, laboratory, sonographic, histologic, immunohistochemical, and clonality results. RESULTS: A monomorphic lymphocytic population (22/22, 100%) and in-depth mucosal infiltration (15/22, 68%) were hallmarks of LGITL. Epithelial patterns (nests and plaques) were significantly more frequent in LGITL (11/22, 50%) than in LPE (1/22, 5%) cases (P = .001). A CD3+ lymphocytic apical-to-basal gradient was observed in 9/22 (41%) of LGITL vs 1/22 (5%) of LPE cases (P = .004). Most LPE cases (17/18, 94%) featured marked fibrosis in the superficial part of the lamina propria. The Ki-67 20%- and 30%-thresholds discriminated between LGITL and LPE within both the epithelium (specificity >95%) and lamina propria (specificity >95%), respectively. All LGITL cases were CD3+ pSTAT3- and pSTAT5+. T-cell receptor gamma chain gene rearrangements indicated monoclonality in 86% of LGITL cases. Surprisingly, 70% of LPE cases featured monoclonality (40%) or monoclonality on a polyclonal background (30%). CONCLUSIONS AND CLINICAL IMPORTANCE: We identified new histologic, immunohistochemical, and clonality criteria to distinguish LGITL from LPE.

Surgical treatment of a distal oesophageal stricture by mucosal radial incision and dilation in a kitten with secondary megaoesophagus.

CASE SUMMARY: A 7-month-old intact female Maine Coon cat was presented with a 2-month history of regurgitations. Contrast radiographic and endoscopic examinations revealed a diffuse megaoesophagus secondary to a severe lower oesophageal stricture. An epiphrenic diverticulum was noted. Endoscopic balloon dilation was unsuccessful. Gastrotomy was thus performed in order to incise the oesophageal wall radially along the stricture site, and then to dilate the stricture. A diameter of 20 mm was reached. With the aim of preventing stricture recurrence, submucosal injections of triamcinolone acetonide were performed. An 18 Fr oesophagogastric feeding tube was placed and a left gastropexy was performed in order to exert some traction on the gastroesophageal junction, with the aim of reducing the oesophageal diverticulum. Twelve months postoperatively, clinical signs had completely resolved and follow-up radiographs revealed marked improvement of the oesophageal dilatation. RELEVANCE AND NOVEL INFORMATION: Lower oesophageal strictures should be considered when evaluating regurgitations or megaoesophagus in a kitten. Surgical mucosal radial incision is a therapeutic option in cases of lower oesophageal stricture refractory to balloon dilation, and can lead to a marked improvement of clinical signs and of the oesophagus diameter leading to clinical success.

Photoproduction of the f_{2}(1270) Meson Using the CLAS Detector.

The quark structure of the f_{2}(1270) meson has, for many years, been assumed to be a pure quark-antiquark (qq[over ¯]) resonance with quantum numbers J^{PC}=2^{++}. Recently, it was proposed that the f_{2}(1270) is a molecular state made from the attractive interaction of two ρ mesons. Such a state would be expected to decay strongly to final states with charged pions due to the dominant decay ρ→π^{+}π^{-}, whereas decay to two neutral pions would likely be suppressed. Here, we measure for the first time the reaction γp→π^{0}π^{0}p, using the CEBAF Large Acceptance Spectrometer detector at Jefferson Lab for incident beam energies between 3.6 and 5.4 GeV. Differential cross sections, dσ/dt, for f_{2}(1270) photoproduction are extracted with good precision due to low backgrounds and are compared to theoretical calculations.

Interpretation of the LHCb P_{c}(4312)

We study the nature of the new signal reported by LHCb in the J/ψp spectrum. Based on the S-matrix principles, we perform a minimum-bias analysis of the underlying reaction amplitude, focusing on the analytic properties that can be related to the microscopic origin of the P_{c}(4312)^{+} peak. By exploring several amplitude parametrizations, we find evidence for the attractive effect of the Σ_{c}^{+}D[over ¯]^{0} channel, which is not strong enough, however, to form a bound state.

Oxygenated C17 polyacetylene metabolites from Algerian Eryngium tricuspidatum L. roots: Structure and biological activity.

The secondary metabolite pattern of Eryngium tricuspidatum has been found to be dominated by C17 acetylene oxylipins, according to the chemistry reported in the literature for the genus Eryngium. Two new oxylipins, 11-acetoxy-falcarindiol (4) and 1,2-dihydro-11-acetoxy-falcarindiol (5) have been isolated, along with main related polyacetylenes 1-3 and the already known monoterpene aldehydes 6-10, from the petroleum ether extract of roots. The structure and the absolute configuration of compounds 4 and 5 have been determined by spectroscopic methods as well as by comparison with related known compounds. Polyacetylenes 1-4 inhibited significantly the in vitro growth of a series of cancer cell lines, ranging from 0.3 to 29 µM, whereas 5 was inactive.

Determination of the Pole Position of the Lightest Hybrid Meson Candidate.

Mapping states with explicit gluonic degrees of freedom in the light sector is a challenge, and has led to controversies in the past. In particular, the experiments have reported two different hybrid candidates with spin-exotic signature, π_{1}(1400) and π_{1}(1600), which couple separately to ηπ and η^{'}π. This picture is not compatible with recent Lattice QCD estimates for hybrid states, nor with most phenomenological models. We consider the recent partial wave analysis of the η^{(')}π system by the COMPASS Collaboration. We fit the extracted intensities and phases with a coupled-channel amplitude that enforces the unitarity and analyticity of the S matrix. We provide a robust extraction of a single exotic π_{1} resonant pole, with mass and width 1564±24±86 and 492±54±102 MeV, which couples to both η^{(')}π channels. We find no evidence for a second exotic state. We also provide the resonance parameters of the a_{2}(1320) and a_{2}^{'}(1700).

Feline low-grade alimentary lymphoma: an emerging entity and a potential animal model for human disease.

BACKGROUND: Low-grade alimentary lymphoma (LGAL) is characterised by the infiltration of neoplastic T-lymphocytes, typically in the small intestine. The incidence of LGAL has increased over the last ten years and it is now the most frequent digestive neoplasia in cats and comprises 60 to 75% of gastrointestinal lymphoma cases. Given that LGAL shares common clinical, paraclinical and ultrasonographic features with inflammatory bowel diseases, establishing a diagnosis is challenging. A review was designed to summarise current knowledge of the pathogenesis, diagnosis, prognosis and treatment of feline LGAL. Electronic searches of PubMed and Science Direct were carried out without date or language restrictions. RESULTS: A total of 176 peer-reviewed documents were identified and most of which were published in the last twenty years. 130 studies were found from the veterinary literature and 46 from the human medicine literature. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. The pathophysiology of feline LGAL still needs to be elucidated, not least the putative roles of infectious agents, environmental factors as well as genetic events. The most common therapeutic strategy is combination treatment with prednisolone and chlorambucil, and prolonged remission can often be achieved. Developments in immunohistochemical analysis and clonality testing have improved the confidence of clinicians in obtaining a correct diagnosis between LGAL and IBD. The condition shares similarities with some diseases in humans, especially human indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. CONCLUSIONS: The pathophysiology of feline LGAL still needs to be elucidated and prospective studies as well as standardisation of therapeutic strategies are needed. A combination of conventional histopathology and immunohistochemistry remains the current gold-standard test, but clinicians should be cautious about reclassifying cats previously diagnosed with IBD to lymphoma on the basis of clonality testing. Importantly, feline LGAL could be considered to be a potential animal model for indolent digestive T-cell lymphoproliferative disorder, a rare condition in human medicine.

HTS-FTIR spectroscopy allows the classification of polyphenols according to their differential effects on the MDA-MB-231 breast cancer cell line.

Breast cancer is a major public health issue among women in the world. Meanwhile new anticancer treatments struggle more and more to be accepted in the pharmaceutical market and research costs still increase. There is therefore a need to find new treatments and new screening methods to test them more quickly and efficiently. Among natural compounds, an increasing interest has been given to polyphenols as they can take action at the different stages of carcinogenesis, from tumour initiation to metastasis formation, by disturbing multiple cellular signalling pathways. They constitute one of the largest groups of plant metabolites and more than 8000 compounds have already been identified based on their chemical structure. Traditionally in pharmacology, new anticancer drugs are first evaluated for their potential to inhibit the proliferation of cancer cell lines. Numerous potential drugs are discarded at this stage even though they could show interesting modes of action. In turn, there is an increasing demand for more systemic approaches in order to obtain a global and accurate insight into the biochemical processes mediated by drugs. Recently, FTIR spectroscopy was demonstrated to be an innovative tool to obtain a unique fingerprint of the effects of anticancer drugs on cells in culture. While this spectral technique appears to have a definite potential to sort drugs according to their spectral fingerprints, characteristic of the metabolic modifications induced, the present challenge remains to evaluate the drug-induced spectral changes in cancer cells on a larger scale. This article presents the results obtained for a 24 h-exposure of the breast cancer cell line MDA-MB-231 to 15 compounds belonging to different classes of polyphenols using FTIR spectroscopy connected to a high throughput screening extension. Through unsupervised and supervised statistical analyses (PCA, MANOVA, Student's t-tests and HCA), a distinction between polyphenol treatments and controls could be well established.

Infrared spectra of primary melanomas can predict response to chemotherapy: The example of dacarbazine.

Metastatic melanomas are highly aggressive and median survival is 6-9months for stage IV patients in the absence of treatment with anti-tumor activity. Dacarbazine is an alkylating agent that has been widely used in the treatment of metastatic melanomas and that could be still used in combination with targeted or immune therapies. Indeed, therapeutic benefits of these treatments in monotherapy are poor and one option to improve them is to combine drugs and/or to better anticipate the individual response to a defined treatment. To our best knowledge and to date, there is no test available to predict the response of a patient to dacarbazine. We show here that examination of melanoma histological sections by infrared micro-spectroscopy reveals the sensitivity of the cancer to dacarbazine. Unsupervised analysis of the FTIR spectra evidences spontaneous and significant clustering of infrared spectra into two groups that match the clinical responsiveness of the patients to dacarbazine used as a first-line treatment. A supervised model resulted in 83% of the patient status (responder/non-responder) being correctly identified. The spectra revealed a key modification in the nature and quantity of lipids in the cells of both groups.

Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity.

Glioblastoma multiforme (GBM) is the most lethal and common malignant human brain tumor. The intrinsic resistance of highly invasive GBM cells to radiation- and chemotherapy-induced apoptosis accounts for the generally dismal treatment outcomes. This study investigated ophiobolin A (OP-A), a fungal metabolite from Bipolaris species, for its promising anticancer activity against human GBM cells exhibiting varying degrees of resistance to proapoptotic stimuli. We found that OP-A induced marked changes in the dynamic organization of the F-actin cytoskeleton, and inhibited the proliferation and migration of GBM cells, likely by inhibiting big conductance Ca(2+)-activated K(+) channel (BKCa) channel activity. Moreover, our results indicated that OP-A induced paraptosis-like cell death in GBM cells, which correlated with the vacuolization, possibly brought about by the swelling and fusion of mitochondria and/or the endoplasmic reticulum (ER). In addition, the OP-A-induced cell death did not involve the activation of caspases. We also showed that the expression of BKCa channels colocalized with these two organelles (mitochondria and ER) was affected in this programmed cell death pathway. Thus, this study reveals a novel mechanism of action associated with the anticancer effects of OP-A, which involves the induction of paraptosis through the disruption of internal potassium ion homeostasis. Our findings offer a promising therapeutic strategy to overcome the intrinsic resistance of GBM cells to proapoptotic stimuli.

Phenazines and cancer.

Phenazines are a large group of natural and synthesised nitrogen-containing heterocycles, including more than 100 different compounds of natural origin and over 6000 synthetic compounds. Many of these compounds have been investigated as potential anti-cancer agents. Despite a large number of research publications, no recent attempt to summarise and critically evaluate the experimental findings relating to the anti-cancer activity of this class of compounds has been made. The present review fills this gap in the literature and discusses both natural and synthetic phenazines with a critical focus on in vitro, in vivo and available clinical anti-cancer activities of these compounds.

Lycorine and its derivatives for anticancer drug design.

Amaryllidaceae alkaloids are extensively studied for their biological activities in several pharmaceutical areas, including, for example, Alzheimer's disease for which galanthamine has already reached the market. Among this chemical family, lycorine displays very promising anti-tumor properties. This review first focuses on the chemical diversity of natural and synthetic analogues of lycorine and their metabolites, and then on mechanisms of action and biological targets through which lycorine and its derivatives display their anti-tumor activity. Our analysis of the structure-activity relationships of this family of compounds highlights the existence of various potential leads for the development of novel anticancer agents.