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This study assessed the protective potential of ascorbic acid against doxorubicin-induced spleen tissue damage in rats. Twenty-eight male Sprague-Dawley rats were divided into four groups. The control group received saline every other day at a dose of 1mL throughout the experiment. The ascorbic acid group was administered 50mg/kg of ascorbic acid daily for 10 days. The doxorubicin group received a single dose of 15mg/kg of doxorubicin on day 7. The ascorbic acid + doxorubicin group received both 50mg/kg of ascorbic acid daily for 10 days and a single dose of 15mg/kg of doxorubicin on day 7. After the experiment, splenic tissue samples were examined histopathologically and immunohistochemically. Histopathological analysis revealed edema, destruction and degeneration in the doxorubicin group, but these changes were alleviated in the ascorbic acid-treated group, approaching control group levels. Immunohistochemical analysis showed increased CD4 + and CD8 + cell immunopositivity in the ascorbic acid + doxorubicin group compared to the doxorubicin group. Biochemical tests indicated that doxorubicin reduced superoxide dismutase activity and increased malondialdehyde levels, whereas ascorbic acid mitigated these effects. The findings suggest that ascorbic acid may have a protective role against doxorubicin-induced spleen injury in rats.

Background: Spleen deficiency syndrome (SDS) is associated with elevated inflammatory factors and dysregulation of gastrointestinal motility hormones and intestinal microbiota. Qushi decoction (QD), a traditional formula, has not been reported using modern scientific research methods for changes in its probiotic fermented QD (FQD) composition and its potential mechanisms to alleviate SDS. Therefore, the aim of this study was to investigate the splenic protection of FQD in SDS rats by modulating gastrointestinal motility hormones and intestinal microbiota., Results: The results showed that FQD increased total polysaccharides, total protein, total flavonoids and the other active ingredients compared to QD, effectively improved splenic inflammation and apoptosis in SDS rats, and modulated gastrointestinal motility hormones to alleviate diarrhea and other symptoms. In addition, the dysregulation of the gut microbiota was reversed by increasing the levels of Bifidobacterium and decreasing the levels of Escherichia-Shigella and Proteobacteria, which may be related to the regulation of bacterial metabolites to alleviate SDS., Conclusion: These results suggest that FQD is an effective formula for improving SDS. Our findings show that FQD beneficial to the implications for the treatment of SDS. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Background: The toxicological effects of fine particulate matter (PM 2.5 ) on the cardiopulmonary and nervous systems have been studied widely, whereas the study of PM 2.5 on systemic toxicity is not in-depth enough. Lipopolysaccharide (LPS) can cause multiple organ damage. The combined effects of co-exposure of PM 2.5 plus LPS on the stomach, spleen, intestine, and kidney are still unclear. Purpose: This study was aimed to explore the toxicological effects of co-exposure of PM 2.5 and LPS on the different organs of mice. Research Design and Study Sample Using a real-ambient PM 2.5 exposure system and an intraperitoneal LPS injection mouse model, we investigated multiple organ damage effects on male BALB/c mice after co-exposure of PM 2.5 plus LPS for 23 weeks in Linfen, a city with a high PM 2.5 concentration in China. Data Collection: Eosin-hematoxylin staining, ELISA and the biochemical assay analysed the toxicological effects. Results: The pathological tissue injury on the four organs above appeared in mice co-exposed to PM 2.5 plus LPS, accompanied by the body weight and stomach organ coefficient abnormality, and significant elevation of pro-inflammatory cytokines levels, oxidative stress in the spleen and kidney, and levels of kidney injury molecule (KIM-1) increase in the kidney. There were tissue differences in the pathological damage and toxicological effects on mice after co-exposure, in which the spleen and kidney were more sensitive to pollutants. In the PM 2.5 + LPS group, the superoxide dismutase inhibition and catalase (CAT) activity promotion in the kidney or spleen of mice were significant relative to the PM 2.5 group; the CAT and interleukin-6 (IL-6) levels in the spleen were raised considerably compared with the LPS group. Conclusions: These findings suggested the severity and sensitivity of multiple organ injuries in mice in response to PM 2.5 plus LPS.

Ethnopharmacological Relevance: Qihuzha granule (QHZG), is one of traditional Chinese patent medicines composed of eleven edible medicinal plant, which has been used in the clinic for the treatment of indigestion and anorexia in children caused by deficiency of the spleen and stomach. Yet it is noteworthy that QHZG has therapeutic effect on recurrent respiratory tract infection (RRTI) in children. However, its potential molecular mechanisms remained unclear., Aim of the Study: The aim of this study was to investigate the therapeutic effect and potential mechanism of QHZG on lipopolysaccharide (LPS) induced acute spleen injury., Materials and Methods: The acute spleen injury model was induced by intraperitoneal injection of LPS (10 mg/kg) and safe doses of QHZG was administered by gavage once a day for 23 days before LPS treatment. Serum inflammatory cytokines including interleukin-2 (IL-2), IL-1β, IFN-γ, and tumor necrosis factor-α (TNF-α) were tested by ELISA. Related protein levels were detected by Western blotting. Hematoxylin-eosin (HE) staining was employed to observe the histological alterations. The distribution of macrophages and neutrophils in the mouse spleen was examined by immunofluorescence analysis., Results: QHZG pretreatment significantly abolished the increased secretion of cytokines such as interleukin-2 (IL-2), IL-1β, IFN-γ, and tumor necrosis factor-α (TNF-α), which were attributable to LPS treatment. Immunofluorescence staining and Histological analysis of spleen tissue revealed the protective effect of QHZG against LPS-induced acute spleen injury in mice. Further study indicated that pretreatment with QHZG significantly inhibited LPS-induced phosphorylation of Src. Accordingly, the increased phosphorylation of Src downstream components (JNK, ERK, P38 and STAT3) induced by LPS was remarkably diminished by QHZG, suggesting the involvement of Src/MAPK/STAT3 pathway in the inhibitory effects of QHZG on spleen injury in mice., Conclusion: Our study demonstrated that QHZG protected mice from LPS-induced acute spleen injury via inhibition of Src/MAPK/Stat3 signal pathway. These results suggested that QHZG might serve as a new drug for the treatment of LPS-stimulated spleen injury., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Methamphetamine (METH) is a strong addictive central nervous system stimulant. METH abuse can alter biological processes and immune functions necessary for host defense. The acquisition and transmission of HIV, hepatitis, and other communicable diseases are possible serious infectious consequences of METH use. METH also accumulates extensively in major organs. Despite METH being a major public health and safety problem globally, there are limited studies addressing the impact of this popular recreational psychostimulant on tissue adaptive immune responses after exposure to T cell dependent [ovalbumin (OVA)] and independent [lipopolysaccharide (LPS)] antigens. We hypothesized that METH administration causes pulmonary and splenic tissue alterations and reduces T cell responses to OVA and LPS in vivo, suggesting the increased susceptibility of users to infection. Using a murine model of METH administration, we showed that METH causes tissue injury, apoptosis, and alters helper and cytotoxic T cell recruitment in antigen challenged mice. METH also reduces the expression and distribution of CD3 and CD28 molecules on the surface of human Jurkat T cells. In addition, METH decreases the production of IL-2 in these T-like cells, suggesting a negative impact on T lymphocyte activation and proliferation. Our findings demonstrate the pleotropic effects of METH on cell-mediated immunity. These alterations have notable implications on tissue homeostasis and the capacity of the host to respond to infection.

Background: Chemotherapy with oxaliplatin is known to induce sinusoidal obstruction syndrome (SOS). In a previous single-center study, we reported that oxaliplatin-induced increase in splenic volume (SV) is strongly indicative of SOS, and that this increase in SV persisted for > 1 year after completing chemotherapy. The aim of this study was to confirm the oxaliplatin-induced SV change in a multicenter study in patients with stage III colon cancer in Japan., Methods: We enrolled 59 patients who underwent curative resection for stage III colon cancer in the FACOS study in a phase II multi-center clinical study. Participants received mFOLFOX6 or CAPOX as adjuvant chemotherapy. SV change was assessed three times by computed tomographic volumetry: before surgery, on completion of adjuvant chemotherapy, and 1 year after completing adjuvant chemotherapy., Results: SV on completing and 1 year after chemotherapy was significantly higher than that before surgery (P < 0.001). Oxaliplatin-induced SOS persisted for > 1 year after the completion of adjuvant chemotherapy in half of the patients. There was no difference in 3-year disease-free survival with respect to the presence or absence of increased SV. An increase in SV was observed in 72% of patients treated with mFOLFOX6 and 94% of patients treated with CAPOX (P = 0.13)., Conclusion: This study can be verified the findings observed in our previous single-center study, oxaliplatin-based adjuvant chemotherapy was associated with an increase in SV. Furthermore, this increase can persist for > 1 year. The continuous presence of SOS may have a negative impact on prognosis in patients that develop recurrent disease.

Background: In the present work, we investigated the effects of aqueous extract of Maca (AEM) on energy metabolism and immunoregulation in spleen-deficient mice., Method: We established a cyclophosphamide-induced spleen-deficiency model with ginseng, a herb that strengthens splenic function, as a control. Sixty male Kunming mice were randomly divided among 5 groups: normal, model, ginseng control (1.5 g/kg), AEM high dose (1.5 g/kg), and AEM low dose (0.75 g/kg). All animals, except those in the normal group, were injected with cyclophosphamide to induce spleen deficiency. Furthermore, we investigated differences in the thermotropic behaviors of mice using the Animal Thermotropism Behavior Surveillance System to detect energy metabolism-related assays and immune regulation assays., Results: Mice given AEM exhibited tropism in response to hot plate exposure. AEM inhibited loss of body weight and immune organ atrophy caused by cyclophosphamide, increased the cAMP/cGMP ratio in blood, and enhanced the activities of Na + -K + -ATPase, Ca 2+ -Mg 2+ -ATPase, lactate dehydrogenase, and hepatic glycogen. AEM significantly reversed declining white blood cells and platelet counts, and increased the hemoglobin content within peripheral blood cells. AEM improved the protein levels of IFN-γ, TNF-β, IL-2, and IL-4 in the spleen., Conclusions: Maca possesses the Traditional Chinese Medicine (TCM) property of warm and appears to strengthen spleen function.

An unusual presentation of sclerosing angiomatoid nodular transformation in a 42-year-old man who was admitted with jaundice, deranged liver function tests and subsequently diagnosed with acute hepatitis C infection in the context of recent intravenous drug use. During his admission, he had an ultrasound of the abdomen followed by a CT thorax, abdomen and pelvis which showed splenomegaly and a large splenic lower pole mass that was hypoechoic and concerning for lymphoma. A bone marrow biopsy showed no evidence of lymphoma and an ultrasound-guided biopsy of the splenic mass suggested unusual features with vascular proliferation, either neoplastic or reactive, with no evidence of lymphoma or high-grade sarcoma. Given the concern for malignancy, an open splenectomy was required to determine the nature of the lesion with histologic findings consistent with a non-neoplastic benign vascular lesion favouring sclerosing angiomatoid nodular transformation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Saccharomyces cerevisiae is an emerging pathogen within the immunocompromised. We present a 4-year-old boy with acute lymphoblastic leukemia presenting with polymerase chain reaction-confirmed hepatosplenic S. cerevisiae infection and significant immune reconstitution symptoms. We explore the challenges of monitoring treatment efficacy using C-Reactive protein, β-D-glucan, and imaging and the administration of chemotherapy alongside antifungals and steroids for control of immune reconstitution syndrome.

Dibutyl phthalate (DBP) is a ubiquitous environmental contaminant that at certain levels can be harmful to human health. Although DBP has been widely linked to immunotoxicity, any association between DBP exposure and splenic injury remains unknown. The purpose of this study was to investigate whether DBP exposure can induce splenic injury and the antagonistic effects of two antioxidants, vitamin E (VitE) and curcumin (Cur), on DBP-induced splenic injury. The levels of ROS, GSH, T-AOC, IL-1β, TNF-α, cytochrome C, caspase-8, caspase-9 and caspase-3 in the spleen homogenate of mice were measured. Any histopathological changes in the spleen were observed using H&E and toluidine blue staining. And the morphology of mitochondria was observed using Janus Green B staining. The results indicate that exposure to 50 mg/kg DBP could cause histopathological changes of the spleen and result in inflammation and apoptosis associated with oxidative stress, which may lead to splenic injury in mice. Moreover, both VitE and Cur could antagonize the oxidative stress induced by DBP to reduce splenic injury. These findings help to expand our understanding of DBP-mediated immunotoxicity, and to show that VitE and Cur can alleviate DBP-induced splenic injury and the possible DBP-associated decline in immune function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aniline exposure leads to neuron and spleen toxicity specifically and makes diverse neurological effects and sarcoma that is defined by splenomegaly, hyperplasia, and fibrosis and tumors formation at the end. However, the molecular mechanism(s) of aniline-induced spleen toxicity is not understood well, previous studies have represented that aniline exposure results in iron overload and initiation of oxidative/nitrosative disorder stress and oxidative damage to proteins, lipids and DNA subsequently, in the spleen. Elevated expression of cyclins, cyclin-dependent kinases (CDKs) and phosphorylation of pRB protein along with increases in A, B and CDK1 as a cell cycle regulatory proteins cyclins, and reduce in CDK inhibitors (p21 and p27) could be critical in cell cycle regulation, which contributes to tumorigenic response after aniline exposure. Aniline-induced splenic toxicity is correlated to oxidative DNA damage and initiation of DNA glycosylases expression (OGG1, NEIL1/2, NTH1, APE1 and PNK) for removal of oxidative DNA lesions in rat. Oxidative stress causes transcriptional up-regulation of fibrogenic/inflammatory factors (cytokines, IL- 1, IL-6 and TNF-α) via induction of nuclear factor-kappa B, AP-1 and redox-sensitive transcription factors, in aniline treated-rats. The upstream signalling events as phosphorylation of IκB kinases (IKKα and IKKβ) and mitogen-activated protein kinases (MAPKs) could potentially be the causes of activation of NF-κB and AP-1. All of these events could initiate a fibrogenic and/or tumorigenic response in the spleen. The spleen toxicity of aniline is studied more and the different mechanisms are suggested. This review summarizes those events following aniline exposure that induce spleen toxicity and neurotoxicity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Doxorubicin (DOX) is a widely used drug for cancer treatment as a chemotherapeutic agent. However, the cellular and integrative mechanism of DOX-induced immunometabolism is unclear. Two-month-old male C57BL/6J mice were divided into high- and low-dose DOX-treated groups with a maintained saline control group. The first group was injected with a high dose of DOX (H-DOX; 15 mg·kg -1 ·wk -1 ), and the second group was injected with 7.5 mg·kg -1 ·wk -1 as a latent low dose of DOX (LL-DOX). H-DOX treatment led to complete mortality in 2 wk and 70% survival in the LL-DOX group compared with the saline control group. Therefore, an additional group of mice was injected with an acute high dose of DOX (AH-DOX) and euthanized at 24 h to compare with LL-DOX and saline control groups. The LL-DOX and AH-DOX groups showed obvious apoptosis and dysfunctional and structural changes in cardiac tissue. Splenic contraction was evident in AH-DOX- and LL-DOX-treated mice, indicating the systems-wide impact of DOX on integrative organs of the spleen, which is essential for cardiac homeostasis and repair. DOX dysregulated splenic-enriched immune-sensitive lipoxygenase and cyclooxygenase in the spleen and left ventricle compared with the saline control group. As a result, lipoxygenase-dependent D- and E-series resolvin precursors, such as 16HDoHE, 4HDoHE, and 12-HEPE, as well as cyclooxygenase-mediated PG species (PGD 2 , PGE 2, and 6-keto-PG 2α ) were decreased in the left ventricle, suggestive of defective immunometabolism. Both AH-DOX and LL-DOX induced splenic contraction and expansion of red pulp with decreased CD169 + metallophilic macrophages. AH-DOX intoxicated macrophages in the spleen by depleting CD169 + cells in the acute setting and sustained the splenic macrophage loss in the chronic phase in the LL-DOX group. Thus, DOX triggers a vicious cycle of splenocardiac cachexia to facilitate defective immunometabolism and irreversible macrophage toxicity and thereby impaired the inflammation-resolution program. NEW & NOTEWORTHY Doxorubicin (DOX) triggered splenic mass loss and decreased CD169 with germinal center contraction in acute and chronic exposure. Cardiac toxicity of DOX is marked with dysregulation of immunometabolism and thereby impaired resolution of inflammation. DOX suppressed physiological levels of cytokines and chemokines with signs of splenocardiac cachexia.

cis-Diamminedichloroplatinum (cisplatin) is an effective chemotherapeutic and is widely used for the treatment of various types of solid tumors. Bio-distribution of cisplatin to other organs due to poor targeting towards only cancer cells constitutes the backbone of cisplatin-induced toxicity. The adverse effect of this drug on spleen is not well characterized so far. Therefore, we have set our goal to explore the mechanism of the cisplatin-induced pathophysiology of the spleen and would also like to evaluate whether carnosine, an endogenous neurotransmitter and antioxidant, can ameliorate this pathophysiological response. We found a dose and time-dependent increase of the pro-inflammatory cytokine, TNF-α, in the spleen tissue of the experimental mice exposed to 10 and 20 mg/kg body weight of cisplatin. The increase in inflammatory cytokine can be attributed to the activation of the transcription factor, NF-ĸB. This also aids in the transcription of other pro-inflammatory cytokines and cellular adhesion molecules. Exposure of animals to cisplatin at both the doses resulted in ROS and NO production leading to oxidative stress. The MAP Kinase pathway, especially JNK activation, was also triggered by cisplatin. Eventually, the persistence of inflammatory response and oxidative stress lead to apoptosis through extrinsic pathway. Carnosine has been found to restore the expression of inflammatory molecules and catalase to normal levels through inhibition of pro-inflammatory cytokines, oxidative stress, NF-ĸB and JNK. Carnosine also protected the splenic cells from apoptosis. Our study elucidated the detailed mechanism of cisplatin-induced spleen toxicity and use of carnosine as a protective agent against this cytotoxic response., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Chemotherapy may induce mass lesion in rare conditions, which can be easily mistaken as a residual tumor mass. In this report, we describe a mass affecting spleen in a patient received chemotherapy for non Hodgkin diffuse large B cell lymphoma. This mass proved histologically to be non neoplastic formed of sheets of histiocytes and xanthoma cells, which is called histiocyte-rich pseudotumor. This report describes this rare lesion and the possible differential diagnosis., (© Copyright Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Aim: Gastro-splenic fistula is a rare entity in which malignant tumors are the primary cause, followed by perforated peptic ulcers and Crohn's disease., Case Report: A 66 years old patient undergoing chemotherapy for gastric large cells B lymphoma presented fever, fatigue and worsening of general conditions. A CT scan showed the presence of an abdominal abscess resulting from a pathological communication between stomach and spleen., Results: En - bloc splenectomy and gastric wedge resection was performed; gastric wall was sutured with a linear stapler. Postoperative stay was uneventful; alimentation was restarted 5 days after the surgical procedure, and the patient was discharged 2 days later, Conclusion: We have described an unusual case of gastric fistula complicating chemotherapy early diagnosed and successfully treated., Key Words: Chemothera Gastrosplenic fistula, Lymphoma, Surgery.

We herein report a rare case of acute bilateral renal and splenic infarctions occurring during chemotherapy for lung cancer. A 60-year-old man presented with acute and intensive upper abdominal and back pain during chemotherapy with cisplatin and etoposide for lung cancer. Contrast-enhanced computed tomography (CT) revealed bilateral renal and splenic infarctions. After the administration of unfractionated heparin his pain was relieved with a clearance of the infarctions in the CT findings and a recovery of renal dysfunction. Enhanced coagulation by lung cancer and arterial ischemia by chemotherapy may therefore contribute to the development of these infarctions.

Background: Visceral leishmaniasis is a disease caused by the protozoan Leishmania sp. and is transmitted by Lutzomyia longipalpis (sand fly). In renal transplant recipients, visceral leishmaniasis causes severe damage to the liver, spleen, and hematopoietic system, as well as poor outcomes for patients with transplanted kidneys. This study describes the largest series of cases of visceral leishmaniasis in renal transplant recipients, providing important information about the diagnostic routines and therapeutic strategies in this patient population., Methods: A retrospective, descriptive study was performed to analyze the distribution and evaluate the extent of the epidemiologic, clinical, diagnostic and therapeutic aspects of 30 renal transplant recipients from endemic regions who presented with visceral leishmaniasis in the post-transplantation period., Results: In this study, visceral leishmaniasis was more frequent in men (80%). The mean age of presentation was 40 ± 10.5 years. The majority of patients worked in urban areas (66.7%), cohabitated with domestic animals (90%), and were from low-income households. In 73.3% of cases, diagnosis was made by direct isolation of Leishmania forms. Patients were treated with liposomal amphotericin, resulting in a high degree of disease remission (80%)., Conclusions: This study describes the largest series of visceral leishmaniasis in renal transplant recipients and expands clinical-epidemiological knowledge for transplantation teams to perform adequate disease management for this specific patient population.

Emergency physicians (EPs) can use bedside ultrasound to diagnosis of intraabdominal free fluid in a variety of clinical scenarios.The purpose of this study is to review the sonographic appearance of intraabdominal free fluid and incidence of spontaneous splenic rupture. An EP used bedside ultrasound to diagnose spontaneous splenic rupture in a patient who had received tissue plasminogen activator for suspected acute ischemic stroke. Bedside ultrasound by a physician trained in basic ultrasound and the focused assessment with sonography for trauma can diagnose intraabdominal free fluid, facilitating appropriate and more rapid consultation, advanced imaging, and treatment.

Rhubarb is often used to establish chronic diarrhea and spleen (Pi)-deficiency syndrome animal models in China. In this study, we utilized the enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) method to detect changes in bacterial diversity in feces and the bowel mucosa associated with this model. Total microbial genomic DNA from the small bowel (duodenum, jejunum, and ileum), large bowel (proximal colon, distal colon, and rectum), cecum, and feces of normal and rhubarb-exposed rats were used as templates for the ERIC-PCR analysis. We found that the fecal microbial composition did not correspond to the bowel bacteria mix. More bacterial diversity was observed in the ileum of rhubarb-exposed rats (P<0.05). Furthermore, a 380 bp product was found to be increased in rhubarb-exposed rats both in faces and the bowel mucosa. The product was cloned and sequenced and showed high similarity with regions of the Bacteroides genome. AS a result of discriminant analysis with the SPSS software, the Canonical Discriminant Function Formulae for model rats was established.

Objective: To report the development of a spontaneous subcapsular splenic hematoma following filgrastim administration in a patient undergoing an allogeneic hematopoietic stem cell transplant., Case Summary: A 60-year-old female with myelodysplastic syndrome was admitted for a reduced-intensity allogeneic hematopoietic stem cell transplant from an unrelated donor. She received filgrastim 5 μg/kg starting on day 1 to accelerate neutrophil recovery. On day 5, she began reporting severe left chest-wall pain. Contrast-enhanced computed tomography of the abdomen/pelvis revealed a spontaneous subcapsular splenic hematoma. Upon discontinuation of filgrastim, the pain fully resolved. The patient was subsequently rechallenged with filgrastim, which led to recurrence of the left-sided chest-wall pain. Filgrastim was discontinued and the patient reported resolution of the pain., Discussion: Filgrastim has been associated with splenic hematoma and splenic rupture, predominantly in healthy donors undergoing mobilization of peripheral blood stem cells. Although splenic rupture attributed to filgrastim in a patient undergoing allogeneic hematopoietic stem cell transplantation has been reported, to our knowledge, this is the first case report to establish causality. Using the Naranjo probability scale, an objective causality assessment revealed that the adverse drug event was highly probable., Conclusions: Although filgrastim-induced splenomegaly, splenic hematomas, and splenic rupture are rare, clinicians working in the bone marrow transplant setting should be cognizant of the potential of growth factors to cause these adverse events.

Dabigatran etexilate (Pradaxa; Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT) is an oral anticoagulant that produces a reliable, dose-dependent anticoagulant effect without the need for routine laboratory monitoring. Dabigatran is a direct thrombin inhibitor, acting like other members in its class (bivalirudin, argatroban) to impede the clotting process through selective and reversible binding with both free and clot-bound thrombin. Dabigatran anticoagulates rapidly: plasma levels peak 2 hours after absorption, with a half-life that ranges between 12 and 17 hours. Dabigatran was approved by the Food and Drug Administration in October 2010 after it compared favorably with warfarin in a large clinical trial studying its efficacy in stroke prevention in atrial fibrillation. Currently, there is no laboratory test on the market by which a physician can quantify the anticoagulation effect of dabigatran, nor is there any antidote to reverse a life-threatening bleed should it occur. We present a case of a patient with splenic hemorrhagic soon after initiation of dabigatran.

The ameliorative effects of Opuntia vulgaris fruit extract (OE) were evaluated against methanol-induced haematological and biochemical toxicity in rats. The methanol-induced haematological and biochemical perturbation significantly decreased the levels of red blood cell (RBC), haemoglobin (Hb), haematocrit (Ht), serum total protein and increased glucose, cholesterol, and triglyceride levels in serum. Treatment of rats with methanol significantly increased lipid peroxidation (LPO) level and decreased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in erythrocytes. OE treatment could increase significantly the levels of RBC, Hb, Ht and total protein, and decrease glucose, cholesterol and triglyceride levels in serum, and increase the activities of SOD, CAT and GPx in erythrocytes, when compared with methanol-treated group. Spleen histopathology showed that OE could significantly reduce the incidence of spleen lesion induced by methanol. These results suggested that OE could exhibit a potential source of natural antioxidants against methanol-induced haematological and biochemical disruption in rats. The protective effects of OE may be due to the modulation of antioxidant enzymes activities and inhibition of LPO.

Nitrogen mustards (HN) and sulphur mustard (SM) are potent alkylating blister inducing chemical warfare agents. Single 1.0 LD50 dose produced a progressive fall in body weight from second day onwards in all groups of mustard agents exposed animals. Histological examination of spleen, liver skin and kidney revealed significant histopathological lesions in nitrogen mustards and sulphur mustard. These lesions include granulovascular degeneration with perinuclear clumping of the cytoplasm of hepatocytes and renal parenchymal cells. Renal lesions were characterized by congestion and hemorrhage. The maximum toxic manifestation were noted in spleen and skin of HN-3 exposed mice while sulphur mustard reported maximum toxicity in liver and kidneys. The study suggests both nitrogen mustards and sulphur mustard to be extremely toxic by percutaneous route based on histopathological observation and can contributed to earlier reported free radical generation by these toxicants.

Aim: To evaluate the adverse effects of flunixin, ketoprofen and phenylbutazone when administered I/V to clinically normal miniature donkeys., Methods: Twenty clinically normal adult (2.0-2.5 years old) male miniature donkeys weighing 113-136 kg and 0.81- 0.86 m tall were randomly assigned to one of four groups, and administered either saline (n=5), 1.0 mg/kg flunixin (n=5), 2.2 mg/kg ketoprofen (n=5), or 4.4 mg/kg phenylbutazone (n=5) I/V at 0800 hours on Day 1, then every 12 h, for 12 days. The animals were observed every 8 h, and examined physically daily. Blood, faeces and urine samples were collected daily from all donkeys, for haematological indices and enzyme activities, occult blood, and urinalysis, respectively. Immediately after euthanasia, complete post-mortem examinations were performed on all donkeys, and gross lesions recorded. Histopathology was conducted on a wide range of tissues., Results: Clinically, mild anorexia and diarrhoea were observed during the study only in donkeys treated with phenylbutazone. There was an effect of treatment with the non-steroidal anti-infl ammatory drugs (NSAID) on red blood cell (RBC) counts, packed cell volume (PCV) and enzyme activities, but not on urine. Lesions were observed in the glandular mucosa of the stomach of all donkeys treated with NSAID, including ulceration in most. Also, in donkeys treated with NSAID, hyperaemia, erosion and ulceration of the gastrointestinal tract, and congestion of the liver, kidney and spleen, were observed. Microscopically, hepatic and renal lesions comprised biliary hyperplasia and interstitial nephritis, respectively., Conclusions and Clinical Relevance: The gastrointestinal, hepatic and renal lesions observed in the donkeys treated with NSAID demonstrated the toxic potential of NSAID, which was greatest for animals treated with phenylbutazone, less for flunixin, and least for ketoprofen. When use of these compounds is contemplated in clinical cases, the risk of adverse effects and the comparative toxic potential should be considered, together with the efficacy of the compound for the condition being treated.

Nano-sized silica is a promising material for disease diagnosis, cosmetics and drugs. For the successful application of nano-sized material in bioscience, evaluation of nano-sized material toxicity is important. We previously found that nano-sized silica particles with a diameter of 70 nm showed acute liver failure in mice. Here, we performed histological analysis of major organs such as the liver, spleen, lung, kidney, brain and heart in mice, chronically injected with 70-nm silica particles for 4 weeks. Histological analysis revealed hepatic microgranulation and splenic megakaryocyte accumulation in these 70-nm silica particles treated mice, while the kidney, lung, brain and heart remained unaffected. Thus, liver and spleen appear to be the major target organs for toxicity by the chronic administration of the 70-nm silica particles.

Objective: To observe the effects of Sijunzi Decoction on D-xylose excretion rate and ATP content in the mucosa membranes of small intestines of rats with spleen deficiency., Methods: Spleen deficiency model rats were made by reserpine injection. D-xylose excretion rate was measured with p-bromoaniline method, and the ATP content of small intestines mucosa was detected with bioluminescence method. The correlation between D-xylose excretion rate and ATP content of mucosa was also analyzed., Results: Rats' body weight and D-xylose excretion rate decreased after reserpine injection (P < 0.01, vs control group), but increased after treated with Sijunzi Decoction (P < 0.05, vs model group). The ATP content of mucosa showed no significant difference between model group and control group. There was obviously positive correlation between the change of urine's D-xylose excretion rate and mucosa ATP content., Conclusion: Sijunzi Decoction has the activity of improving xylose absorption in spleen deficiency rats, but no obvious effect on their mucosa ATP content. The reducing of urine's D-xylose excretion rate in spleen deficiency rats is accompanied with the decrease of mucosa ATP content.

We report the case of a 56 years old male patient, smoker, obese, with untreated arterial hypertension, hospitalized on 16.02.07 with the diagnosis of inferior acute myocardial infarction, for which he received thrombolysis with streptokinase, followed by anticoagulation with non fractioned heparin. Two days later he started to complain of acute abdominal pain, and laboratory findings showed a low hemoglobin level. Imaging findings (ultrasonography and CT scan) showed evidence of subcapsular liver haematoma, caused by bleeding at hepatic and splenic level. He received red blood packed cells, fresh frozen plasma, cryoprecipitate, activated factor VII and was transferred by helicopter to Fundeni Clinical Institute--Intensive care unit (ICU). On admission, the patient was conscious, anxious, dyspneic, with mild hypoxia, with no signs of low cardiac output and with a painful abdomen. ECG, echocardiography and elevated myocardial necrosis enzymes confirmed myocardial infarction. Shortly after admission there was a worsening of his clinical condition, with a decrease in hemoglobin level despite red blood packed cells administration (Hb=7.8 g/dl) and thrombocytopenia (82000/mmc), with normal coagulation tests, thus suggesting active intraabdominal bleeding. Echography and CT scan confirmed bleeding. Emergency surgery was performed, showing massive haemoperitoneum (approx 4.5 L of blood), due to spontaneous rupture of a subcapsular hematoma in the liver. The surgical hemostasis was performed on the liver parenchyma laceration. Duration of surgery was 4 hours. There were no significant cardiac events during surgery (no signs of ischemia on ECG, no ST elevation), despite the need for inotropic agent. After surgery, the patient was referred to the ICU, intubated and ventilated, with inotropic support - dobutamine. Sequential ECG's, enzymatic trend and echocardiographies were performed to monitor myocardial ischemia. The outcome was favourable, no further bleeding and no postoperative myocardial infarction occurred. Secondary prevention was started early (thromboprophylaxis, selective beta-blocker, angiotensin inhibitors and statins). The patient had a favorable outcome and was discharged from the ICU the fourth day after surgery. He had a total length of stay in hospital of seven days, with a follow-up in the cardiology department.

Aniline exposure causes toxicity to the spleen, which leads to a variety of sarcomas, and fibrosis appears to be an important preneoplastic lesion. However, early molecular mechanisms in aniline-induced toxicity to the spleen are not known. Previously, we have shown that aniline exposure results in iron overload and induction of oxidative stress in the spleen, which can cause transcriptional upregulation of fibrogenic/inflammatory cytokines via activation of oxidative stress (OS)-responsive signaling pathways. To test this mechanism, male SD rats were treated with aniline (1mmol/kg/day via gavage) for 7 days, an experimental condition that precedes the appearance of fibrosis. Significant increases in both NF-kappaB and AP-1 binding activity was observed in the nuclear extracts of splenocytes from aniline-treated rats as determined by ELISAs, and supported by Western blot data showing increases in p-IkappaBalpha, p-p65 and p-c-Jun. To understand the upstream signaling events which could account for the activation of NF-kappaB and AP-1, phosphorylation patterns of IkappaB kinases (IKKalpha and IKKbeta) and mitogen-activated protein kinases (MAPKs) were pursued. Our data showed remarkable increases in both p-IKKalpha and p-IKKbeta in the splenocytes from aniline-treated rats, suggesting their role in the phosphorylation of both IkappaBalpha and p65 subunits. Furthermore, aniline exposure led to activation of all three classes of MAPKs, as evident from increased phosphorylation of extracellular-signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK1/2) and p38 MAPKs, which could potentially contribute to the observed activation of both AP-1 and NF-kappaB. Activation of upstream signaling molecules was also associated with simultaneous increases in gene transcription of cytokines IL-1, IL-6 and TNF-alpha. The observed sequence of events following aniline exposure could initiate a fibrogenic and/or tumorigenic response in the spleen.

Gastrosplenic fistula resulting from erosion of a primary splenic lymphoma is a very rare cause of massive upper gastrointestinal hemorrhage as compared to benign peptic ulcer disease, gastric Crohn's disease, gastric adenocarcinoma, and primary gastric and splenic lymphomas. This hemorrhage can be successfully managed by splenic artery embolization, followed by splenectomy and gastric resection. A 50-year-old patient developed a gastrosplenic fistula during a course of chemotherapy for differentiated histiocytic lymphoma. The fistula was demonstrated by CT scan with oral contrast. The fistula was followed endoscopically and noted to have closed spontaneously with confirmed closure at laparotomy. The clinical management of this complication is discussed, and the literature pertaining to this rare condition is reviewed.

We experienced a case of danazol-induced splenic peliosis. A 42-year-old woman had taken danazol for refractory aplastic anemia for 2 years. Her anemia gradually became aggravated, and the patient complained of intermittent left upper-abdominal pain. Because computed tomography scanning showed multiple blood-filled cavities in the enlarged spleen without intraperitoneal hemorrhage, a splenectomy was emergently performed. This report is the first of a case of splenic peliosis developing during danazol therapy for aplastic anemia. The possible association between the administration of anabolic steroids or danazol and the development of peliosis is discussed.

Food mycotoxin deoxynivalenol (vomitoxin, DON) produced by Fusarium graminearum and F. culmorum can induce rapid diminution of lymphoid tissues and lymphopenia in the growing chickens and mammals. We first investigated the direct acute effects of DON on the chick immune-related embryo tissues such as embryonic liver and spleen. Direct DON administration into the embryonic eggs caused toxin accumulation in liver in a time-dependent manner. Electron microscopic observation showed a notable accumulation of fat droplet in the liver tissue and the re-exposed hatched chicken showed more distinguishing enlarged fat globules, so-called fatty cysts like human steatosis. Regarding effects of deoxynivalenol on the chick embryonic spleen, fatty change was also observed in splenocytes. Functionally, mitogen-stimulated cellular and humoral lympho-proliferations were suppressed in the DON-treated embryo. Conclusively, acute direct exposure to deoxynivalenol in the chick embryo caused toxic histological alterations in the liver and spleen and suppressed in vitro lymphoblastogenesis.

The combination of cisplatin (CDDP) and 5-fluorouracil (5-FU) has been reported to show marked therapeutic effects on experimental tumors and human malignancies, such as head and neck cancer. In these clinical studies, CDDP was administered on day 1 and followed by a 5-d continuous infusion of 5-FU. However, it was repeatedly shown that the sequence of 5-FU followed by CDDP is more active and less toxic in tumor-bearing animals. Thus, the optimal administration schedule of CDDP and 5-FU against L1210 murine leukemia was examined and compared with that of the combination of 5-FU and carboplatin (JM-8). The combinations of 5-FU (days 1 to 5) and CDDP, given either on day 1 or on day 5, showed a similar level of antitumor activity and toxicity. On the other hand, the combinations of 5-FU (days 1 to 5) and JM-8 given on day 5 showed significantly higher antitumor activity and rather less toxicity, as compared with the combinations on the reverse sequence. Thus, the treatment sequence of platinum compounds followed by a 5-d continuous infusion of 5-FU in many clinical studies appears to be extremely favorable to CDDP than JM-8. In addition, pathological examinations of died mice showed that accumulation of ascites and pleural effusion was inhibited most effectively by JM-8, given alone or in combination with 5-FU. These results strongly suggest that the combination of 5-FU followed by JM-8 will be expected to show more excellent antitumor activity against human malignancies, and may be especially useful in patients who are unable to tolerate CDDP-related toxicity.

Exposure to aniline results in selective toxicity to the spleen, leading to a variety of sarcomas on chronic exposure in rats, and fibrosis appears to be an important initiating preneoplastic lesion of the spleen. However, the molecular mechanism(s) by which aniline leads to fibrogenic response is not well understood. Previously, we have shown that aniline exposure leads to iron overload and induction of oxidative stress in the spleen. We hypothesized that aniline-induced oxidative stress in the spleen causes transcriptional up-regulation of fibrogenic cytokines via activation of redox-sensitive transcription factor, nuclear factor-kappa B (NF-kappa B). To test this hypothesis, male SD rats were treated with 0.5 mmol/kg/day aniline hydrochloride via drinking water for 30 days. Cytokine mRNAs were measured by real-time quantitative PCR, while cytokine release was determined in the supernatants of the cultured splenocytes using specific ELISAs. IL-1alpha, IL-6, and TNF-alpha mRNA levels showed 6.9-, 2.9-, and 2.6-fold increases, respectively, in the spleens of aniline-treated rats in comparison to the controls. The increases in mRNA levels were associated with enhanced secretion of these cytokines in the splenocyte culture supernatants. NF-kappa B p65 level in the nuclear extracts of cultured splenocytes of aniline-treated rats showed a 2-fold increase in comparison to the controls as quantitated by NF-kappa B p65-specific ELISA. The binding activity of NF-kappa B, determined by electrophoretic mobility shift assay (EMSA), also showed an increase in NF-kappa B binding in the nuclear extracts of the splenocytes from aniline-treated rats. The specificity of NF-kappa B binding was further confirmed by supershift assays. The results indicate that aniline exposure causes enhanced expression of IL-1alpha, IL-6, and TNF-alpha, both at mRNA and protein levels, suggesting their role in splenic fibrosis. Also, the increased NF-kappa B binding activity suggests that up-regulation of these cytokines in the spleen is a redox-dependent mechanism.

Objective: The research was designed to study the meridian tropism theory of traditional Chinese drug through experiments in animals., Method: We used the mouse model of deficient spleen as the object. After administering Atractylodes macrocephala and Poria cocos respectively, we measured the indexes of MDA, SOD, NO to observe the effects of the drugs on various organs and compared the results with the traditional meridian tropism theory., Result: The two drugs had selective effects on the quantity or activity of MDA, SOD, NO in the organs for the normal group and the model group., Conclusion: The selective influence of the two drugs has close relativity with the traditional meridian tropism theory.

To determine the reversibility of hematological and pathological changes in spleen induced by sub-chronic administration of chlorpropham (CIPC), male F344 rats were given CIPC in the diet at 0, 600, 3000 or 15,000 ppm for 13 weeks (administration period) and then were given standard (0 ppm) diet for 10 weeks (recovery period). At 0, 1, 2, 4 or 10 weeks in the recovery period, 5 rats in each groups were examined for hematology and pathology. At the end of CIPC administration, dose-dependent and significant methemoglobinemia, anemia, splenomegaly and pathological lesions indicating hemolytic anemia were observed in all the treated groups. The hematological changes, congestion of red pulp, lymphoid atrophy, increased extramedullary hematopoiesis in spleen and hematopoietic cell hyperplasia in bone marrow were diminished during the 10 weeks recovery period. However, increased hemosiderin deposition and capsular fibrosis in spleen of the treated groups remained at the end of recovery period. The results indicated that hematological changes induced by sub-chronic administration of CIPC were reversible but hemosiderin deposition and fibrosis in spleen were not reversible in the recovery period examined, suggesting the significance of splenic lesion in CIPC-toxicity.

In this study, thirty male Wistar rats/group were exposed nose-only to mean analytical concentrations of 9.2, 32.4, 96.5, and 274.9 mg aniline/m3 using an exposure regimen of 6 h/day, 5 days/week for 2 weeks (days 0-11), followed by a 2-week post-exposure period (up to day 28). Serial sacrifices for specialized examinations were performed on days 0, 4, 11, 14, and 28. Clinical signs of toxicity, body weights, hematology, and clinical chemistry tests, including total iron in liver and spleen, splenic lipid peroxidation, organ weights, gross and histological changes in target organs were recorded. No mortality was observed during the study. Rats exposed to 96.5 mg/m3 and above displayed cyanosis, with no apparent progression during the exposure period. The predominant manifestation of toxicity was methemoglobin formation and associated erythrocytotoxicity. The changes observed included anemia, red blood cell morphological alterations (e.g., Heinz bodies), decreased hemoglobin and hematocrit, reticulocytosis, and effects on the spleen (splenomegaly, hemosiderin accumulation, and increased hematopoietic cell proliferation), which gained significance at 96.5 and 274.9 mg/m3. With regard to increased splenic extramedullary hematopoiesis, borderline effects occurred at 32.4 mg/m3. The total content of iron in spleen homogenates increased in a concentration-dependent and time-dependent manner with increasing duration of exposure. The maximum accumulation of iron in the liver and spleen exceeded the respective control levels by approximately 60% and approximately 500%, respectively. Splenic lipid peroxidation and total iron were highly correlated (r2 = 0.93) toward the end of the exposure period. A hepatic hemosiderosis was observed at 274.9 mg/m3. Thus, in regard to erythrocytotoxicity and associated increased splenic sequestration of erythrocytes, iron accumulation and lipid peroxidation 32.4 mg/m3 constitutes the no-observed-adverse-effect concentration (NOAEC). However, spleens of the 32.4 mg/m3 exposure group exhibited a minimal increase in extramedullary hematopoiesis. Exposure to 9.2 mg/m3 was not associated with any significant effect.

Actinomycosis is a gram-positive anaerobic bacterium. Actinomyces organisms are important constituents of the normal flora of mucous membranes and are considered opportunistic pathogens. The three major clinical presentations of actinomycosis include the cervicofacial, thoracic, and abdominopelvic regions. Actinomycosis infection in patients with febrile neutropenia is uncommon and actinomycosis splenic involvement in acute leukemia patients is very rare. We describe a man with acute myeloid leukemia and splenic actinomycotic abscess that developed after chemotherapy following prolonged neutropenia.

The mechanism behind amyloid formation is unknown in all types of amyloidosis. Several substances can enhance amyloid formation in animal experiments. To induce secondary systemic amyloid (AA-type amyloid) formation, we injected silver nitrate into mice together with either amyloid fibrils obtained from patients with familial polyneuropathy (FAP) type I or polyethylene glycol (PEG). Mice injected with silver nitrate only served as controls. Amyloid deposits were detectable at day 3 in animals injected with amyloid fibrils and in those injected with PEG, whereas in control mice, deposits were not noted before day 12. Our results indicate that amyloid fibrils from FAP patients and even a non-sulfate containing polysaccharide (PEG) have the potential to act as amyloid-enhancing factors.

Hepatosplenic candidiasis (HSC) is an emerging complication of the treatment of patients with acute leukemia. Treatment of this infection can be very difficult and data on the duration of antifungal therapy are not available. We evaluated the efficacy of amphotericin B lipid complex (ABLC) for the treatment of five patients with acute leukemia and HSC. The dose of the administered ABLC ranged between 5 and 11 mg/kg per day and the median duration of therapy was 4.3 months. Four patients had complete response to the above treatment with resolution of fever and improvement in the radiologic findings. One patient refused to continue treatment and subsequently died with relapsed leukemia and disseminated Candida infection. Preliminary data suggest that ABLC is a well-tolerated and effective treatment for HSC and should be considered for phase II trials as front line treatment for this type of deep seated fungal infections.