RESUMEN
In 2018, the dietary exposure bioaccumulation fish test of the Organization for Economic Co-operation and Development Test Guideline No. 305 was introduced into Japan's Chemical Substances Control Law. The Japanese government has adopted a single definitive testing criterion for the absence of high bioaccumulation: the growth-corrected kinetic dietary magnification factor (BMFKg) must be less than 0.007. The aim of this study was to decrease regulatory restrictions in order to increase newly developed chemical substances and their subsequent approval of their manufacture and import, i.e., the present study was motivated by concerns over the criterion being too restrictive, rather than scientific concerns, such as uncertainty in criterion. We used statistical post-processing to assess the possibility of expanding the criteria for not being highly bioaccumulative. Based on our results, we proposed the criterion that the test substance should be considered not highly bioaccumulative if the following two conditions are met: (1) The ratio of the maximum to the minimum measured 5% lipid-standardized biomagnification factor at the end of the uptake phase (BMF5%, n = 5) for the test substance and reference substance should be less than 3.0, and (2) For the measured BMF5% of the test substance (n = 5), the probability that the next (the sixth) BMF5% is below 0.0334 should exceed 95% based on statistical post-processing. It is worth noting that the BMF5% values should only be applied for non-ionizable lipid soluble compounds. Application of our suggested approach to Japan implies that the criterion for chemical substances that are not highly bioaccumulative in the dietary exposure bioaccumulation fish test would be increased from 0.007 to 0.0149.
Asunto(s)
Exposición Dietética , Contaminantes Químicos del Agua , Animales , Bioacumulación , Japón , Peces , Lípidos , Contaminantes Químicos del Agua/análisisRESUMEN
Intestinal ischemia/reperfusion (I/R) injury is a life-threatening complication that leads to inflammation and remote organ damage. The NLRP3 inflammasome regulates the caspase-1-dependent release of IL-1ß, an early mediator of inflammation after I/R injury. In this study, we investigated the role of the NLRP3 inflammasome in mice with intestinal I/R injury. Deficiency of NLRP3, ASC, caspase-1/11, or IL-1ß prolonged survival after intestinal I/R injury, but neither NLRP3 nor caspase-1/11 deficiency affected intestinal inflammation. Intestinal I/R injury caused acute lung injury (ALI) characterized by inflammation, reactive oxygen species generation, and vascular permeability, which was markedly improved by NLRP3 deficiency. Bone marrow chimeric experiments showed that NLRP3 in non-bone marrow-derived cells was the main contributor to development of intestinal I/R-induced ALI. The NLRP3 inflammasome in lung vascular endothelial cells is thought to be important to lung vascular permeability. Using mass spectrometry, we identified intestinal I/R-derived lipid mediators that enhanced NLRP3 inflammasome activation in lung vascular endothelial cells. Finally, we confirmed that serum levels of these lipid mediators were elevated in patients with intestinal ischemia. To our knowledge, these findings provide new insights into the mechanism underlying intestinal I/R-induced ALI and suggest that endothelial NLRP3 inflammasome-driven IL-1ß is a novel potential target for treating and preventing this disorder.
Asunto(s)
Lesión Pulmonar Aguda/metabolismo , Células Endoteliales/metabolismo , Inflamasomas/metabolismo , Pulmón/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Daño por Reperfusión/metabolismo , Animales , Caspasa 1/metabolismo , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
PURPOSE: The aim of this study was to evaluate both the intestinal mucosa staple line integrity and anastomotic leak pressure after healing in a porcine survival model. METHODS: We used two suture models using two different size staples (incomplete mucosal closure model: group G [staple height 0.75 mm], complete mucosal closure model: group B [staple height 1.5 mm]) in the porcine ileum. Five staple lines were created in each group made in the ileum for each model, and the staple sites harvested on days 0, 2, and 7. The leak pressure at the staple site was measured at each time point. RESULTS: On day 0, the leak pressure for group G (79.5 mmHg) was significantly lower than that for group B (182.3 mmHg) (p < 0.01). On days 2 and 7, there was no significant difference between groups G and B (171 mmHg and 175.5 mmHg on day 2, 175.5 mmHg and 175.5 mmHg on day 7, p > 0.05). The histological findings in both groups showed similar healing at postoperative days 2 and 7. CONCLUSION: The integrity of the mucosal staple lines was associated with the postoperative leak pressure on day 0. However, there was no association with the leak pressure at two days or more postoperatively in a porcine model.
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Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Fuga Anastomótica/etiología , Fuga Anastomótica/fisiopatología , Mucosa Intestinal/fisiopatología , Mucosa Intestinal/cirugía , Presión , Grapado Quirúrgico/efectos adversos , Suturas/efectos adversos , Cicatrización de Heridas/fisiología , Animales , Modelos Animales de Enfermedad , Íleon , PorcinosRESUMEN
Although the intimate linkage between hypoxia and inflammation is well known, the mechanism underlying this linkage has not been fully understood. Nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is an intracellular multiprotein complex that regulates interleukin-1ß (IL-1ß) secretion and pyroptosis, and is implicated in the pathogenesis of sterile inflammatory diseases. Here, we investigated the regulatory mechanism of NLRP3 inflammasome activation in response to hypoxia in macrophages. Severe hypoxia (0.1% O2 ) induced the processing of pro-IL-1ß, pro-caspase-1, and gasdermin D, as well as the release of IL-1ß and lactate dehydrogenase in lipopolysaccharide (LPS)-primed murine macrophages, indicating that hypoxia induces NLRP3 inflammasome-driven inflammation and pyroptosis. NLRP3 deficiency and a specific caspase-1 blockade inhibited hypoxia-induced IL-1ß release. Hypoxia-induced IL-1ß release and cell death were augmented under glucose deprivation, and an addition of glucose in the media negatively regulated hypoxia-induced IL-1ß release. Under hypoxia and glucose deprivation, hypoxia-induced glycolysis was not driven and subsequently, the intracellular adenosine triphosphates (ATPs) were depleted. Atomic absorption spectrometry analysis showed a reduction of intracellular K+ concentrations, indicating the K+ efflux occurring under hypoxia and glucose deprivation. Furthermore, hypoxia and glucose deprivation-induced IL-1ß release was significantly prevented by inhibition of K+ efflux and KATP channel blockers. In vivo experiments further revealed that IL-1ß production was increased in LPS-primed mice exposed to hypoxia (9.5% O2 ), which was prevented by a deficiency of NLRP3, an apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1. Our results demonstrate that NLRP3 inflammasome can sense intracellular energy crisis as a danger signal induced by hypoxia and glucose deprivation, and provide new insights into the mechanism underlying hypoxia-induced inflammation.
Asunto(s)
Glucosa/metabolismo , Hipoxia/metabolismo , Inflamasomas/metabolismo , Macrófagos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Apoptosis/efectos de los fármacos , Caspasa 1/metabolismo , Muerte Celular/efectos de los fármacos , Células Cultivadas , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Potasio/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury is a life-threatening complication that leads to inflammation and remote organ damage. However, the underlying mechanism is not yet fully understood. Toll-like receptor 5 (TLR5) is highly expressed in mucosa and recognizes flagellin, the main component of the bacterial flagella. Here, we investigated the role of TLR5 in inflammation and tissue damage after intestinal I/R injury using TLR5-deficient mice. METHODS AND RESULTS: Intestinal levels of TLR5 mRNA and flagellin protein were elevated in wild-type mice subjected to intestinal I/R. Although TLR5 deficiency had no effect on intestinal flagellin levels, it significantly attenuated intestinal injury and inflammatory responses after intestinal I/R. TLR5 deficiency also markedly improved survival in mice after intestinal I/R injury. In wild-type mice, intestinal I/R injury induced remote organ damage, particularly in the lung, which was attenuated by TLR5 deficiency. Furthermore, TLR5 deficiency prevented lung inflammatory responses and vascular permeability after intestinal I/R injury. CONCLUSION: These findings demonstrate a novel role of TLR5 and provide new insights into the mechanism underlying inflammation and tissue damage after intestinal I/R injury.
Asunto(s)
Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Daño por Reperfusión/metabolismo , Receptor Toll-Like 5/metabolismo , Animales , Inflamación/patología , Mucosa Intestinal/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Daño por Reperfusión/patologíaRESUMEN
Accumulating evidence suggests that IL-1ß plays a pivotal role in the pathophysiology of hepatic ischemia-reperfusion (I/R) injury; however, the mechanism by which I/R triggers IL-1ß production in the liver remains unclear. Recent data have shown that neutrophils contribute to hepatic I/R injury independently of the inflammasomes regulating IL-1ß maturation. Thus, we investigated the role of neutrophils in IL-1ß maturation and tissue injury in a murine model of hepatic I/R. IL-1ß was released from the I/R liver and its deficiency reduced reactive oxygen species generation, apoptosis, and inflammatory responses, such as inflammatory cell infiltration and cytokine expression, thereby resulting in reduced tissue injury. Depletion of either macrophages or neutrophils also attenuated IL-1ß release and hepatic I/R injury. In vitro experiments revealed that neutrophil-derived proteinases process pro-IL-1ß derived from macrophages into its mature form independently of caspase-1. Furthermore, pharmacological inhibition of serine proteases attenuated IL-1ß release and hepatic I/R injury in vivo. Taken together, the interaction between neutrophils and macrophages promotes IL-1ß maturation and causes IL-1ß-driven inflammation in the I/R liver. Both neutrophils and macrophages are indispensable in this process. These findings suggest that neutrophil-macrophage interaction is a therapeutic target for hepatic I/R injury and may also provide new insights into the inflammasome-independent mechanism of IL-1ß maturation in the liver.
Asunto(s)
Comunicación Celular/inmunología , Interleucina-1beta/inmunología , Hepatopatías/inmunología , Hígado/inmunología , Macrófagos/inmunología , Neutrófilos/inmunología , Daño por Reperfusión/inmunología , Animales , Caspasa 1/genética , Caspasa 1/inmunología , Comunicación Celular/genética , Interleucina-1beta/genética , Hígado/patología , Hepatopatías/genética , Hepatopatías/patología , Macrófagos/patología , Ratones , Ratones Noqueados , Neutrófilos/patología , Daño por Reperfusión/genética , Daño por Reperfusión/patologíaRESUMEN
We have conducted animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade and Industry of Japan. Here we conducted a combined repeated-dose and reproductive/developmental toxicity screening test of benzene, 1,1'-oxybis-, tetrapropylene derivs. (BOTD). BOTD was administered to 9-week-old Crl:CD(SD) male and female rats by gavage at 0, 40, 200, or 1000 mg/kg/day. Males were treated for 42 days including mating period. Females were treated for 42-53 days through the premating, mating, pregnancy, and until Day 4 of lactation periods. Increases in prothrombin time and activated partial thromboplastin time values were observed only in males at 200 and 1000 mg/kg/day. Hypertrophy of centrilobular hepatocytes was observed with increased liver weight in both sexes at 200 and 1000 mg/kg/day, but there was no histologic evidence of hepatotoxicity. Diffuse hypertrophy of follicular cells in thyroid glands was observed in females at 200 mg/kg/day and in both sexes at 1000 mg/kg/day, with an increased blood cholesterol level in females at 1000 mg/kg/day. The conception index was decreased for females at 1000 mg/kg/day; and no abnormalities were detected in the reproductive indices of implantation, delivery, or pups' condition, although a slight increase in the pups' body weight was noted at birth. Our data indicate a no-observed-adverse-effect level of 40 mg/kg/day for repeated-dose toxicity on the basis of the prolongation of blood coagulating time, and of 200 mg/kg/day for reproductive/developmental toxicity on the basis of the decreased conception index.
Asunto(s)
Benceno/toxicidad , Reproducción/efectos de los fármacos , Animales , Coagulación Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos/efectos de los fármacos , Femenino , Hígado/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
We have carried out animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade, and Industry of Japan. Here, we tested 1-tert-butoxy-4-chlorobenzene in a combined repeat-dose and developmental and reproductive toxicity test. The test chemical was administered daily by gavage to 9-week-old Crl:CD (SD) rats at doses of 0, 20, 100, and 500 mg/kg/d. Males were treated for 42 d beginning 14 d before mating. Females were treated from 14 d before mating to day 4 of lactation. Decreased spontaneous locomotion, decreased respiratory rate, and incomplete eyelid opening were observed at 500 mg/kg/d (both sexes), but resolved within 30 min of administration, suggesting central nervous system depression. No notable changes were observed in body weight, food consumption, functional battery tests, or blood test. Increased liver weight with centrilobular or diffuse hepatocyte hypertrophy was observed at 100 and 500 mg/kg/d (both sexes). There were no biochemical or histopathological changes related to hepatotoxicity. Increased kidney weight with basophilic tubules, tubule dilatation, and increased hyaline droplets were observed in males dosed at 100 and 500 mg/kg/d. Immunohistochemical staining indicated α2u-globulin nephropathy, a male rat-specific toxicity. Although kidney weight was also increased in females dosed at 500 mg/kg/d, it was not considered to be an adverse effect because there were no histopathological changes. Pup weights on postnatal day 0 were decreased at 500 mg/kg/d and still decreased on postnatal day 4. Our data indicated the no-observed-adverse-effect-level for repeated-dose and reproductive/developmental toxicity for 1-tert-butoxy-4-chlorobenzene was 100 mg/kg/d.
Asunto(s)
Clorobencenos/toxicidad , Exposición Materna/efectos adversos , Exposición Paterna/efectos adversos , Éteres Fenílicos/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Reproducción/efectos de los fármacos , Administración Oral , Animales , Animales Recién Nacidos , Peso Corporal/efectos de los fármacos , Clorobencenos/administración & dosificación , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos/efectos de los fármacos , Femenino , Masculino , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos , Especificidad de Órganos , Éteres Fenílicos/administración & dosificación , Embarazo , Ratas Sprague-Dawley , Pruebas de ToxicidadRESUMEN
Supplemental oxygen inhalation is frequently used to treat severe respiratory failure; however, prolonged exposure to hyperoxia causes hyperoxic acute lung injury (HALI), which induces acute respiratory distress syndrome and leads to high mortality rates. Recent investigations suggest the possible role of NLRP3 inflammasomes, which regulate IL-1ß production and lead to inflammatory responses, in the pathophysiology of HALI; however, their role is not fully understood. In this study, we investigated the role of NLRP3 inflammasomes in mice with HALI. Under hyperoxic conditions, NLRP3(-/-) mice died at a higher rate compared with wild-type and IL-1ß(-/-) mice, and there was no difference in IL-1ß production in their lungs. Under hyperoxic conditions, the lungs of NLRP3(-/-) mice exhibited reduced inflammatory responses, such as inflammatory cell infiltration and cytokine expression, as well as increased and decreased expression of MMP-9 and Bcl-2, respectively. NLRP3(-/-) mice exhibited diminished expression and activation of Stat3, which regulates MMP-9 and Bcl-2, in addition to increased numbers of apoptotic alveolar epithelial cells. In vitro experiments revealed that alveolar macrophages and neutrophils promoted Stat3 activation in alveolar epithelial cells. Furthermore, NLRP3 deficiency impaired the migration of neutrophils and chemokine expression by macrophages. These findings demonstrate that NLRP3 regulates Stat3 signaling in alveolar epithelial cells by affecting macrophage and neutrophil function independent of IL-1ß production and contributes to the pathophysiology of HALI.
Asunto(s)
Lesión Pulmonar Aguda/metabolismo , Proteínas Portadoras/genética , Hiperoxia/metabolismo , Interleucina-1beta/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/patología , Animales , Proteínas Portadoras/metabolismo , Hiperoxia/genética , Hiperoxia/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/patología , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/patologíaRESUMEN
Inflammation plays a key role in the pathophysiology of hepatic ischemia-reperfusion (I/R) injury. However, the mechanism by which hepatic I/R induces inflammatory responses remains unclear. Recent evidence indicates that a sterile inflammatory response triggered by I/R is mediated through a multiple-protein complex called the inflammasome. Therefore, we investigated the role of the inflammasome in hepatic I/R injury and found that hepatic I/R stimuli upregulated the inflammasome-component molecule, nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), but not apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). NLRP3(-/-) mice, but not ASC(-/-) and caspase-1(-/-) mice, had significantly less liver injury after hepatic I/R. NLRP3(-/-) mice showed reduced inflammatory responses, reactive oxygen species production, and apoptosis in I/R liver. Notably, infiltration of neutrophils, but not macrophages, was markedly inhibited in the I/R liver of NLRP3(-/-) mice. Bone marrow transplantation experiments showed that NLRP3 not only in bone marrow-derived cells, but also in non-bone marrow-derived cells contributed to liver injury after I/R. In vitro experiments revealed that keratinocyte-derived chemokine-induced activation of heterotrimeric G proteins was markedly diminished. Furthermore, NLRP3(-/-) neutrophils decreased keratinocyte-derived chemokine-induced concentrations of intracellular calcium elevation, Rac activation, and actin assembly formation, thereby resulting in impaired migration activity. Taken together, NLRP3 regulates chemokine-mediated functions and recruitment of neutrophils, and thereby contributes to hepatic I/R injury independently of inflammasomes. These findings identify a novel role of NLRP3 in the pathophysiology of hepatic I/R injury.
Asunto(s)
Proteínas Portadoras/inmunología , Hígado/inmunología , Neutrófilos/inmunología , Daño por Reperfusión/inmunología , Animales , Apoptosis/inmunología , Western Blotting , Proteínas Portadoras/metabolismo , Quimiotaxis de Leucocito , Citometría de Flujo , Inmunohistoquímica , Inflamasomas/inmunología , Hígado/metabolismo , Hígado/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR , Neutrófilos/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Daño por Reperfusión/patología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
It is well known that perfluorooctane sulfonate (PFOS) preferentially accumulates in the plasma of wildlife and humans. Although earlier studies have suggested that this was due to binding of PFOS to a plasma protein, definite characterization of the protein in in vivo exposure studies was not conducted thus far. In this study, we conducted both in vitro and in vivo experiments to identify PFOS binding protein in the plasma of fish. For the in vivo studies, PFOS was administered intraperitoneally to tiger pufferfish, Takifugu rubripes, and the plasma was separated by ammonium sulfate fractionation. High concentrations of PFOS were found in the 65-70 percent ammonium sulfate fraction (190ng/mL). After SDS-PAGE and N-terminal amino acid sequence analysis, the PFOS-binding protein was identified as an apolipoprotein A-I, which was confirmed on the basis of a significant correlation to the PFOS concentration in each fraction. The plasma samples fractionated by ammonium sulfate from untreated pufferfish were subjected to PFOS binding assay by the equilibrium dialysis method. The results further confirmed that the 60-65 percent ammonium sulfate fraction showed a high PFOS-binding ratio, similar to that found from in vivo studies. We demonstrated that PFOS is likely bound to an apolipoprotein A-I in the plasma of tiger pufferfish in in vivo and in vitro studies.
Asunto(s)
Ácidos Alcanesulfónicos/metabolismo , Proteínas Portadoras/metabolismo , Fluorocarburos/metabolismo , Takifugu/metabolismo , Animales , Apolipoproteína A-I/sangre , Apolipoproteína A-I/metabolismo , Proteínas Sanguíneas/química , Proteínas Sanguíneas/metabolismo , Proteínas Portadoras/sangre , Electroforesis en Gel de Poliacrilamida , Takifugu/sangreRESUMEN
In the present study using rats, we demonstrated that central and peripheral administration of des-acyl ghrelin induced a decrease in the surface temperature of the back, and an increase in the surface temperature of the tail, although the effect of peripheral administration was less marked than that of central administration. Furthermore, these effects of centrally administered des-acyl ghrelin could not be prevented by pretreatment with [D-Lys3]-GHRP-6 GH secretagogue receptor 1a (GHS-R1a) antagonists. Moreover, these actions of des-acyl ghrelin on body temperature were inhibited by the parasympathetic nerve blocker methylscopolamine but not by the sympathetic nerve blocker timolol. Using immunohistochemistry, we confirmed that des-acyl ghrelin induced an increase of cFos expression in the median preoptic nucleus (MnPO). Additionally, we found that des-acyl ghrelin dilated the aorta and tail artery in vitro. These results indicate that centrally administered des-acyl ghrelin regulates body temperature via the parasympathetic nervous system by activating neurons in the MnPO through interactions with a specific receptor distinct from the GHS-R1a, and that peripherally administered des-acyl ghrelin acts on the central nervous system by passing through the blood-brain barrier, whereas it exerts a direct action on the peripheral vascular system.
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Temperatura Corporal/efectos de los fármacos , Sistema Nervioso Central/metabolismo , Ghrelina/administración & dosificación , Sistema Nervioso Periférico/metabolismo , Animales , Aorta/efectos de los fármacos , Arterias/efectos de los fármacos , Bloqueo Nervioso Autónomo , Vías de Administración de Medicamentos , Masculino , N-Metilescopolamina/administración & dosificación , Parasimpatolíticos/administración & dosificación , Ratas , Ratas Wistar , VasodilataciónRESUMEN
A 6-day-old male Japanese Black calf presented with a transverse fracture of the left calcaneus. In calcaneal fractures, traction of the gastrocnemius muscle causes substantial displacement of the proximal fracture fragment; therefore, external fixation alone is prone to failure of fusion or deformed fusion. Furthermore, internal fixation alone may result in refracture due to the high load on the implant. Therefore, internal and external fixation were used to treat the fracture. Bone fusion was observed on postoperative day 50; the wire was removed on postoperative day 90. Radiographic examination at 4 months postoperatively revealed that the bone had fused in normal alignment. Therefore, a good prognosis can be expected for calcaneal fractures treated with combined internal and external fixation.
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Calcáneo , Fracturas Óseas , Animales , Masculino , Fijadores Externos/veterinaria , Fijación de Fractura/veterinaria , Resultado del Tratamiento , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Fracturas Óseas/veterinaria , Fijación Interna de Fracturas/veterinaria , Calcáneo/diagnóstico por imagen , Calcáneo/cirugíaRESUMEN
Medical records of 16 Japanese Black calves with respiratory signs associated with perinatal rib fracture were analyzed, retrospectively, to speculate criteria of surgical intervention for the disease. For this analysis, the severity of respiratory condition was classified into three grades: Grade 1, with no wheezing, Grade 2, with wheezing after excitement but not at rest and Grade 3, with wheezing at rest. Grade 1 (n=3) received only conservative management. Seven of Grade 2 (n=8) and all of Grade 3 (n=5) had surgical management. Clinical outcome was good in all of Grade 1, and the surgical success rate was 83% in other groups. Our result suggests that surgical intervention should be considered for cases with more the severity of Grade 2.
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Enfermedades de los Bovinos , Enfermedades Respiratorias , Fracturas de las Costillas , Embarazo , Femenino , Bovinos , Animales , Fracturas de las Costillas/cirugía , Fracturas de las Costillas/veterinaria , Fracturas de las Costillas/complicaciones , Estudios Retrospectivos , Enfermedades Respiratorias/complicaciones , Enfermedades Respiratorias/veterinaria , Enfermedades de los Bovinos/cirugíaRESUMEN
Of intracranial tumors, primary central nervous system lymphoma (PCNSL) is rare in dogs. Herein, we describe our experience with two dogs (a 3-year-old intact female toy poodle and a 5-year-old spayed female toy poodle) that developed neurological symptoms. Magnetic resonance imaging (MRI) revealed intracranial disseminated lesions. Cerebrospinal fluid (CSF) examination revealed pleocytosis and B-cell monoclonal proliferation in both cases. PCNSL or secondary central nervous system lymphoma (SCNSL) was diagnosed on the basis of MRI findings and CSF examinations. Nimustine (ACNU) is a nitrosourea alkylating agent, a class of drugs that includes lomustine. Nimustine is mainly used to treat human intracranial neoplasia because of its high permeability across the blood-brain barrier. The dogs in this study were treated with combined chemotherapy comprising nimustine and prednisolone, which achieved complete or nearly complete remission of neurological symptoms and long-term survival (>2583 days and 1218 days), but with problematic adverse effects. We determined that the dose of nimustine for canine PCNSL or SCNSL with intravenous infusion was 25-30 mg/m2 every 3-4 weeks for a total of four times; however, the data were insufficient to determine the optimal regimen.
RESUMEN
BACKGROUND: The aim of this study was to evaluate the effect of staple height and rectal wall thickness on the development of an anastomotic leak after laparoscopic low anterior resection performed with the double stapling technique. METHODS: One hundred ninety-nine patients treated from 2013 to 2021 were enrolled. Patients were divided into two groups: those who developed an anastomotic leak (AL (+)) and those who did not (AL (-)). Clinicopathological factors were compared between the groups. RESULTS: Anastomotic leaks were observed in 8/199 patients (4%). A 1.5 mm linear stapler was used for 35/199 patients (17%), 1.8 mm for 89 (45%), and 2 mm for 75 (38%). In the AL (+) group (n = 8), lower staple height (1.5 mm or 1.8 mm) was used more frequently than in the AL (-) group (n = 191). Rectal wall thickness and the rectal wall thickness to staple height ratio was significantly (p < .05) greater in the AL (+) group. However, rectal wall thickness was significantly (p < .05) greater in patients who received neoadjuvant treatment and those with advanced T stage (T3,4) lesions. CONCLUSION: Linear stapler staple height and rectal wall thickness are significantly associated with the development of an anastomotic leak after laparoscopic low anterior resection. Larger staples should be selected in patients with a thicker rectal wall due to neoadjuvant treatment or adjacent advanced rectal tumors.
Asunto(s)
Laparoscopía , Proctectomía , Neoplasias del Recto , Humanos , Fuga Anastomótica/epidemiología , Fuga Anastomótica/etiología , Fuga Anastomótica/prevención & control , Recto/cirugía , Neoplasias del Recto/cirugía , Neoplasias del Recto/etiología , Proctectomía/métodos , Laparoscopía/métodos , Grapado Quirúrgico/métodos , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Carp (Cyprinus carpio L.) was exposed to perfluorinated compounds (PFCs)-perfluoroalkyl carboxylic acids (number of carbon atoms, C = 8, 11, 12, 14, 16, and 18) and perfluorooctane sulfonate (PFOS)-in bioconcentration tests to compare the bioconcentration factors (BCFs) and physicochemical properties of each specific compound. Despite having the same number of carbon atoms (C = 8), the BCFs of perfulorooctanoic acid (PFOA) and PFOS differed by more than two orders of magnitude (PFOA BCF = < 5.1 to 9.4; PFOS BCF = 720 to 1300). The highest BCFs were obtained from perfluorododecanoic acid (BCF = 10,000 to 16,000) and perfluorotetradecanoic acid (BCF = 16,000 to 17,000). The longest observed depuration half-lives were for perfluorohexadecanoic acid (48 to 54 days) and PFOS (45 to 52 days). The concentrations of PFCs were highest in the viscera, followed by the head, integument, and remaining parts of the test fish. PFCs concentrations in the integument, which was in direct contact with the test substances, were relatively greater than that of other lipophilic substance (hexachlorobenzene). It is likely that Clog P would be a better parameter than log K (ow) for the prediction of BCFs for PFCs. Threshold values for PFCs bioaccumulation potential (molecular weight = 700, maximum diameter = 2 nm) seemed to deviate from those generally reported because of the specific steric bulk effect of molecule size.
Asunto(s)
Ácidos Alcanesulfónicos/química , Ácidos Alcanesulfónicos/farmacocinética , Carpas/metabolismo , Fluorocarburos/química , Fluorocarburos/farmacocinética , Contaminantes Químicos del Agua/química , Animales , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacocinética , Cabeza , Ácidos Láuricos/química , Ácidos Láuricos/farmacocinética , Relación Estructura-Actividad , Distribución Tisular , Contaminantes Químicos del Agua/farmacocinéticaRESUMEN
Existing regulatory criteria for bioaccumulation assessment of chemicals are mainly based on a bioconcentration factors (BCF) not a biomagnification factors (BMF). We performed dietary exposure tests for nine poorly water-soluble chemicals and developed a linear regression between the 5 % lipid normalized BCF (BCF(L)) and the lipid-corrected BMF (BMF(L)). The BMF(L) of substances with BCF(L) = 5,000 was 0.31 (95 % CI 0.11-0.87), whereas the BCF(L) of substances with BMF(L) = 1 was 13,000 (95 % CI 5,600-30,000). Five substances can be considered very bioaccumulative (vB) according to the BCF end point (BCF > 5,000), but only two substances were recognized to biomagnify according to the BMF end point (BMF ≥ 1). Although our results are highly suggestive of a relationship between BCF and BMF, additional BMF and trophic magnification factor data for chemicals are required to support this relationship, and new techniques (e.g., fugacity approach) may help in resolving the apparent contradiction in hazard categorization.
Asunto(s)
Carpas/metabolismo , Monitoreo del Ambiente/métodos , Contaminación de Alimentos , Contaminantes Químicos del Agua/farmacocinética , Animales , Cadena Alimentaria , Modelos Lineales , SolubilidadRESUMEN
A 17-month-old Japanese Black cow presented with inappetence, wheezing, dysphagia, and drooling. Radiography and ultrasonography revealed an oval, dorsal, pharyngeal mass, with an internal horizontal line demarcating the radiolucent area from the radio-opaque area. Upper airway endoscopy revealed pus-like deposits in the dorsal nasal passage, hyperemia, and edema in the dorsal pharynx, leading to swelling and airway obstruction. Manual palpation, after sedation, revealed a thickened mass surface, which was difficult to rupture with manual pressure. After inserting a linear sonographic probe through the mouth to establish the vascularity surrounding the mass and to identify a relatively thin-walled area, a trocar was pierced into the mass under endoscopic guidance, and the opening was enlarged manually. The mass was filled with stale pus-like material, which was removed manually. The abscess cavity was washed using saline and povidone-iodine. Day 1 post-surgery, dysphagia and wheezing disappeared. Day 16 post-surgery, endoscopy showed significant improvement in the airway patency. One year postoperatively, the owner reported that the cow had an uneventful recovery. For deep abscesses, such as bovine pharyngeal abscesses, it is important to perform a preoperative transoral Doppler ultrasonography to assess the vascularity and thickness of the abscess wall for safe trocar insertion and abscess drainage.