Megavoltage radiotherapy effects on organs of the reticuloendothelial system

Purpose: To study the uptake capacity of cells from the reticuloendothelial system after irradiation with high-energy X-rays. Methods: Eighteen male Wistar rats were distributed in three groups: group A (n = 6): control, unirradiated animals studied alongside animals from group B; group B (n = 6) and group C (n = 6): animals irradiated and studied after 24 and 48 hours, respectively. The rats were anesthetized and placed on a 10 MV linear accelerator. Next, they were irradiated in the abdominal region, with 8 Gy. Twenty-four (groups A and B) and 48 hours later (group C), a colloidal carbon solution (1 mL/kg) was intravenously injected in the tail vein. Fifty minutes later, the spleens and livers were withdrawn and prepared to be studied. Kupffer cells and splenic macrophages containing carbon pigments were counted in an optical microscope. Arithmetic means were calculated for each group and compared among them. Results: X-rays were associated with a reduced number of Kupffer cells containing colloidal carbon, proliferation and enlargement of biliary ducts, hypoplasia, and hepatocyte necrosis. In the irradiated spleen, the colloidal carbon uptake was concentrated in the marginal zone around the white pulp, with an inexpressive uptake of pigments by macrophages from white and red pulps. Conclusions: The X-rays in the rat abdomen are associated with a reduction in the Kupffer cells uptake of colloidal carbon, hepatocyte disorders, bile duct proliferation, and splenic uptake of colloidal carbon concentrated in the marginal zone.

Depression and Mania Induce Pro-inflammatory Activation of Macrophages Following Application of Serum from Individuals with Bipolar Disorder

OBJECTIVE: Evidence has suggested that immune imbalance is involved with bipolar disorder (BD); however, its precise mechanism is poorly understood. This study investigated whether biochemical changes in the serum from BD patients could modulate the phenotype of cultured macrophages. METHODS: Eighteen subjects with BD and five healthy individuals were included in this study. The human monocyte cell line U-937 was activated with phorbol 12-myristate 13-acetate (PMA) and polarization was induced with RPMI-1640 media supplemented with 10% serum from each patient for 24 hours. Gene expression of selected M1 and M2 markers was assessed by quantitative PCR. RESULTS: Macrophages exposed to serum of manic and depressive BD patients displayed an increase of interleukin-1β (6.40±3.47 and 9.04±5.84 vs. 0.23±0.11; p < 0.05) and tumor necrosis factor-α (2.23±0.91 and 2.03±0.45 vs. 0.62±0.24; p=0.002 and p=0.004, respectively) compared to euthymic group (there was no difference between euthymic and controls). In parallel, U-937 macrophages treated with serum of patients in acute episode displayed a down-regulation of CXCL9 (0.29±0.20 vs. 1.86±1.61; p=0.006) and CXCL10 expression (0.36±0.15 and 0.86±0.24 vs. 1.83±0.88; p < 0.000 and p=0.04) compared to the euthymia group. CONCLUSION: Our results are consistent with previous studies showing that changes in peripheral blood markers could modulate M1/M2 polarization in BD. The evidence of macrophages as source of inflammatory cytokines might be helpful to unravel how the mononuclear phagocyte system is involved in the etiology of BD.

Clinical Features of Serious Adverse Drug Reactions in a Tertiary Care Hospital in Korea / 대한내과학회지

BACKGROUND/AIMS: Several studies have reported on the clinical aspects of adverse drug reactions (ADRs). To date, no study has evaluated serious adverse drug reactions (SADRs) in Korea. The current study evaluates the clinical expression of SADRs in a Korean hospital. METHODS: We reviewed a total of 3,386 cases of SADR occurring between March 2012 and November 2015 in a single tertiary care institution (Regional Pharmacovigilance Center). RESULTS: When classified by organ system, the most common SADRs were white cell and reticuloendothelial system disorders (n = 511). Skin/appendage (n = 296) and gastrointestinal (n = 216) disorders were the fourth- and eighth-most common SADRs, respectively. The three most common single symptoms were leukopenia (n = 499 events), hypotension (n = 444) and anaphylaxis (n = 215). Leukopenia was mainly caused by anti-tumor drugs, followed by piperacilin/tazobactam (n = 28), vancomycin (n = 10) and methimazole (n = 6). Hypotension was most often caused by propacetamol injection (n = 145), while anaphylaxis was mainly caused by cefaclor (n = 19), ranitidine (n = 12), iopamidol (n = 10) and multi-vitamin infusion (n = 9). CONCLUSIONS: Significant differences were noted in the clinical aspects of ADRs and SADRs. Additional studies are warranted to further assess SADRs in response to frequently used causative drugs.

Study of enzyme replacement therapy for Gaucher Disease: comparative analysis of clinical and laboratory parameters at diagnosis and after two, five and ten years of treatment

Objective: To evaluate the impact of enzyme replacement therapy for Gaucher Disease on clinical and laboratory parameters after two, five and ten years of treatment. Methods: Data were collected from patient records and analyzed using BioEstat software (version 5.0). Student's t-test, Analysis of Variance (ANOVA), Wilcoxon test and Kruskal–Wallis test were used for statistical analysis. Hepatomegaly and splenomegaly were analyzed using the Kappa test. Results: There was a significant increase in hemoglobin levels (p-value <0.01) and platelet counts (p-value = 0.01) within two years of therapy. At the same time, the frequencies of splenomegaly (p-value <0.01) and hepatomegaly (p-value <0.05) reduced. These results were similar at five and ten years of enzyme replacement therapy. Conclusions: There are substantial and quick (within two years) laboratory and clinical responses to enzyme replacement therapy. These improvements continue as long as enzyme replacement therapy is administered every two weeks, as recommended by the literature...

Hemolytic anemia presenting as hemoglobinuria from intentional paradichlorobenzene mothball ingestion

A 24-year-old Filipino male was diagnosed with hemolytic anemia when he presented with abrupt onset of anemia, hemoglobinuria, and increased bilirubins, after intentionally ingesting mothballs containing paradichlorobenzene. He was transfused with six units of packed red blood cells (PRBC) and was discharged improved. Paradichlorobenzene, a known oxidant, causes denaturation and precipitation of hemoglobin. These precipitates form Heins bodies within the erythrocytes that are removed by the reticuloendothelial system, fragmenting cells to produce hemoytic anemia from paradicholorobenzene ingestion as confirmed by the UP-National Poison Management and Control Center.

A review on the influences of size and surface charge of liposome on its targeted drug delivery in vivo / 药学学报

Liposomes can be cleared by the reticuloendothelial system (RES) when it is in the blood circulation in the body. And they can accumulate in the organs rich in RES in the body by passive targeting. Targeting of the liposomes is an important factor for its use as a drug carrier, and particle size as well as surface charge are important for its in vivo targeting. In this paper, studies on the influences of particle size and surface charge of the liposomes on cell binding and phagocytosis mechanism were reviewed. A comprehensive review on passive targeting effect of the particle size and surface charge of liposomes on blood, liver, spleen as well as tumor tissue was made. At last, an outlook for future research directions was made.

Existing problems and strategies in liposome-mediated nucleic acid delivery / 药学学报

Liposome-mediated nucleic acid delivery has been a focus recently, but in the course of delivering nucleic acid, some hurdles seriously limit the nucleic acid exerting treatment effect. This review refers to a series of problems such as low blood stability, reticuloendothelial system absorption, the lower targeting of liposome and the restriction of endosomal escape which are suffered in liposome-mediated nucleic acid delivery; and gives a detail introduction of strategies such as PEGylation, ligand modification, photochemical internalization, the application of degradation liposome and membrane-lytic peptide, to overcome those problems.

Septic Knee Arthritis Caused by Group B Salmonella Species in a Patient with Systemic Lupus Erythematosus / 대한정형외과학회잡지

Infection is a leading cause of death in patients with systemic lupus erythematosus (SLE). Insufficiency of the reticuloendothelial system, immunosuppressive therapy and inadequate opsonization are the main predisposing factors for infection. Salmonella infection is one of the most common opportunistic bacterial infections in patients with SLE and it can provoke a bacteremia or a localized infection. We report here on a rare case of septic knee arthritis caused by Group B Salmonella in a SLE patient, and this was treated with arthroscopic irrigation and antibiotics.

A Case of External Auditory Canal Stenosis in Langerhans Cell Histiocytosis

Langerhans cell histiocytosis (LCH) refers a group of disorders of the reticuloendothelial system characterized by a proliferation of histiocytes, which includes eosinophilic granuloma, Lettere-Siwe diseases, and Hand-Schuler Christian disease. The clinical presentation of LCH depends on the site of involvement. It can range from multifocal lesions to a solitary lesion. Tissues characteristically involved in LCH are bone, skin, lung, liver, spleen, bone marrow, lymph nodes and the hypothalamic-pituitary region, although the involvement of other organs such as the bowel can occur. We experienced a case of external auditory canal stenosis in LCH of multiple organ involvement in a 28-year-old male, and report it with a review of the relevant literature.

A Case of External Auditory Canal Stenosis in Langerhans Cell Histiocytosis

Langerhans cell histiocytosis (LCH) refers a group of disorders of the reticuloendothelial system characterized by a proliferation of histiocytes, which includes eosinophilic granuloma, Lettere-Siwe diseases, and Hand-Schuler Christian disease. The clinical presentation of LCH depends on the site of involvement. It can range from multifocal lesions to a solitary lesion. Tissues characteristically involved in LCH are bone, skin, lung, liver, spleen, bone marrow, lymph nodes and the hypothalamic-pituitary region, although the involvement of other organs such as the bowel can occur. We experienced a case of external auditory canal stenosis in LCH of multiple organ involvement in a 28-year-old male, and report it with a review of the relevant literature.

Research advance on hemophagocytic lymphohistiocytosis / 中国实验血液学杂志

Hemophagocytic lymphohistiocytosis (HLH) is named as hemophagocytic syndrome (HPS) and is a complicated disease with reactive hyperplasia of mononuclear/macrophagocytic system. This disease characterised by release of massive cytokines and severe functional destruction of visceral organs, which results from immune function disturbance causing by various pathogenic factors. The cardinal clinical symptoms of HLH are prolonged fever, hepatosplenomegaly, cytopenia, elevated ferritin and triglycerides, low fibrinogen, symptom in nerve system and so on. Nevertheless, impaired function of natural killer cells and cytotoxic T-cell is characteristic for HLH. HLH has of two different types that may be difficult to distinguish from one another: a primary and a secondary form. The combined immunochemotherapy of dexamethasone, etoposide and cyclosporin A and hematopoietic stem cell transplantation are considered as the effective therapies for HLH. In this article, the recent advance in research on the etiological factors, pathogenesis, clinical manifestations, laboratory examination, diagnosis as well as recommended therapy of HLH were reviewed.

Characterization of the Proliferated Histiocytes in Acute Leukemia by Performing Immunohistochemistry

BACKGROUND: The bone marrow biopsy sections of acute leukemia patients occasionally reveal a proliferation of large mononuclear cells that accompany the leukemic blasts, and this proliferation shows a starry sky pattern. We characterized these large mononuclear cells by performing immunohistochemistry with 12 different antibodies. The clinical characteristics were examined and then we determined their difference from hemophagocytic lymphohistiocytosis (HLH) and malignant histiocytic disorders. METHODS: Of the 200 acute leukemic bone marrow biopsy samples, 11 ALL and 10 AML cases showed large mononuclear cell proliferations. The panel of antibodies used for immunohistochemistry included those against the mononuclear phagocyte system, and immunohistochemistry was performed on the patients' initial specimens and the complete remission specimens. 10 normal specimens, 4 initial CML specimens and their complete hematologic response specimens were included as controls. RESULTS: The large mononuclear cells showed immunohistochemical results consistent with histiocytes. They were negative for the markers of dendritic cells the histiocytes and cytokines that are involved in the pathogenesis of HLH and vascular proliferation. Histiocyte proliferation was not observed in the complete remission specimens and in the initial and complete hematological response specimens of the CML patients and the normal bone marrow specimens. None of the cases fulfilled the criteria of HLH, and all 5 ALL cases, for which the immunophenotype results were available, showed a B cell phenotype. CONCLUSION: We characterized the large mononuclear cell proliferations as reactive histiocyte proliferations and we differentiated these from those of secondary HLH and malignant histiocytic disorders. A proportion of the large mononuclear cells showed negative results for all 12 antibodies and they showed characteristics that were suggestive of small fat cells. The pathophysiology and the prognostic effect of the reactive histiocyte proliferation accompanying acute leukemia require further study.

Preparation of PEG-modified nanostructured lipid carriers loaded with hydroxycamptothecin and tissue distribution in mice / 药学学报

Hydroxycamptothecin (HCPT) loaded PEG modified nanostructured lipid carriers (HCPT-PEG-NLC) and nanostructured lipid carriers (HCPT-NLC) were prepared by melt emulsification and homogenization method. The morphology, particle size and encapsulation efficiency of them were investigated. HCPT concentrations in plasma, heart, liver, spleen, lung, kidney and ovary were determined after iv of HCPT injection, HCPT-PEG-NLC and HCPT-NLC in mice. The targeting indexes of HCPT-PEG-NLC and HCPT-NLC were calculated. The transmission electron microscope imaging showed that HCPT-PEG-NLC and HCPT-NLC exhibited a spherical shape. The particle sizes of them were (88.6 +/- 22.5) and (127.2 +/- 43.4) nm. The encapsulation efficiency were (90.51 +/- 3.29)% and (84.37 +/- 2.81)%, respectively. After iv injection into the tail vein of mice, HCPT plasma concentrations of HCPT-PEG-NLC and HCPT-NLC were higher than that of HCPT injection at each sampling time. They also showed longer elimination time in every tissue. HCPT-NLC accumulated in endothelial system (RES), Re and Ce of it in liver and spleen were significantly higher than HCPT-PEG-NLC. HPCT-PEG-NLC prolonged circulation time and increased bioavailability of HCPT. MRT and AUC0-24 h of it were 19.80 and 17.02 times higher than those of HCPT injection. It also significantly reduced phagocytosis of RES, and showed lung targeting effect (Re and Ce were 14.51 and 41.35). To summarize, HCPT-PEG-NLC could prolong the circulation time of HCPT in vivo, and had the lung targeting effect. It was a promising carrier to increase therapeutic effect of HCPT in treating lung cancer.

Infecção em cão por Brucella abortus: relato de caso / Brucella abortus infection in dog: case report

Brucella abortus infection is reported in a dog from a rural area that presented at clinical evaluation left testicular enlargement and right testicular decrease. Serum resulted negative to rapid agglutination test and agar gel immunodifusion with Brucella ovis antigen but positive to buffered plate agglutination test, tube agglutination test and 2- Mercapthoetanol with B. abortus antigen. Brucella isolation was negative in blood, testicular material, semen and urine. Brucella DNA was detected in PCR from urine and blood

Isolated Splenic Metastasis of Sigmoid Colon Cancer Detected by 18F-FDG PET/CT / 핵의학분자영상

Splenic metastasis from colon carcinoma are rare and usually occur in the presence of disseminated visceral metastasis. The liver is the most common site of metastatic spread from colon cancer. Several hypotheses have attempted to explain the low incidence of splenic metastasis. It should be difficult for colorectal cancer cells to reach the spleen through the portal venous system, in which the blood flow is usually from the spleen to the liver. Reticuloendothelial system or rhythmic contraction of the spleen may squeeze out the tumor in the spleen. The absence of afferent lymphatic to the spleen, phagocytic activity and humoral anticancer substances are considered to be other reason for low incidence of splenic metastasis. We report the case of 18F-FDG PET/CT finding in a 70-year-old woman who develop isolated splenic metastasis of sigmoid colon cancer.

A comparative study of the clinical features and hematobiochemical indices between the lung-uptake group and the non-lung-uptake group of malarial patients undergoing liver scanning / 대한내과학회지

BACKGROUND: Lung uptake during liver scanning has been considered as a passing phenomenon related to several diseases, and especially infectious diseases and malignancy. Some reports have shown diffuse lung uptake during liver scanning of malarial patients. Therefore, we tried to determine the relationship between the abnormalities of the clinical features, including the hematobiochemical indices and the lung uptake during liver scanning, by analyzing the information of the malarial patients. METHODS: We performed 99mTechnethium(Tc)-sulfur colloid liver scanning on 20 of the 45 malarial patients who were admitted from 1999 to 2004. We divided them into two groups, the Lung-Uptake (LU) group and the Non-Lung-Uptake (NLU) group. We analyzed the hematobiochemical indices and clinical features, including the respiratory symptoms, between the two groups. RESULTS: 10 of the 20 malarial patients showed lung uptake on the liver scan. The mean platelet counts were 74,000/L and 165,000/L, respectively, in the LU group and the NLU group (p=0.012). Also, the mean total cholesterol levels were 80.3 mg/dL and 105.7 mg/dL, respectively, in the LU group and the NLU group (p=0.033). The scores ofthe bone marrow (BM) uptake in the LU group were higher than those in the NLU group (p=0.008). Yet the other values such as Hb, ALT, albumin and total bilirubin were not statistically significant, nor were the peak body temperatureand other features. CONCLUSIONS: Half of the patients had lung uptake on the liver scanning, and this may be considered as a characteristic of vivax malaria. The BM uptake during liver scanning in the LU group was more increased, and this is supposed to be a consequence of hyperstimulated reticuloendothelial system, which was accompanied by thrombocytopenia and a lower level of total cholesterol in malarial patients.

Perfil de resistência da bactéria da espécie Serratia marcescens isolada de infecções hospitalares no Hospital Geral de Fortaleza ( H.G.F. ) / Resistance profile of the Serratia marcescens bacterium species isolated in hospital infections within the Fortaleza General Hospital ( H.G.F. )

Serratia marcescens é o membro mais importante desse gênero e é geralmente associado a uma variedade de infecção humana, em particular pneumonia e septicemia em pacientes com câncer reticulo endotelial que recebem quimioterapia. Às vezes,esse microrganismo também provoca infecções do trato urinário e infecções em ferimentos. Devido à virulência potencial de espéciesde Serratia, é importante que esses microrganismos sejam separados do grupo Enterobacter. A produção de Dnase extracelular detectável por espécies de Serratia é uma característica confiável, através da qual essa separação pode ser feita. O objetivo deste trabalho foi verificar o perfil de resistência de cepas de Serratia isoladas em pacientes com infecção hospitalar no Hospital Geral de Fortaleza. Foram pesquisados todos os casos de infecção hospitalar na UTI e Berçário, no período de 1o de janeiro a 30 de dezembro de 2002, no Hospital Geral de Fortaleza. As Bactérias isoladas foram identificadas por meio do aparelho de automação MicroScan. Para tal, foramutilizados Painéis Convencionais BreakPoint Combo e ID tipo 2, e painéis Convencionais Liofilizados MicroScan® Liofilizados MIC/Combo 14, destinados à determinação da susceptibilidade a agentes antimicrobianos. A UTI e o Berçário são dois locais onde ocorreram a frequência da bactéria Serratia marcescens (3,44). O setor que apresentou maior resistência a antibióticos foi o berçário,sendo resistente a vários antibióticos de ultima geração. A UTI apresentou mais sensibilidade, incluindo aos antibióticos de ultima geração.

The effects of high-dose intravenous immunoglobulin on plasma protein and lipid levels in the patients with Kawasaki disease / 소아과

PURPOSE: The reticuloendothelial system is composed of sinusoidal capillaries, through which even large protein molecules are freely movable between plasma and interstitial space, including the lymphatic system. Therefore, high-dose intravenous immunoglobulin (IVIG) would cause a redistribution of proteins between two compartments. To investigate this hypothesis, we measured plasma protein and lipid levels in patients with Kawasaki disease before and after high-dose IVIG treatment. METHODS: Thirty four children with Kawasaki disease who had complete responses to high-dose IVIG treatment (1 g/kg/day for two consecutive days), were analyzed. Before and after the administration of IVIG, serum analyses were performed for such parameters as total protein, albumin, gamma-globulins (IgG, IgM, IgA), alpha1-, alpha2-, and beta-globulin fractions, and lipid profiles (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride). RESULTS: The levels of gamma-globulins including IgG, IgM, IgA were significantly increased, and IgG was increased by 1,779+/-304 mg/dL after two-dose of IVIG infusion. The levels of albumin, alpha1-, alpha2-, and beta-globulin fractions were significantly decreased by 18 percent, 24 percent, 19 percent and 12 percent, respectively. HDL-cholesterol level was significantly decreased by 20 percent, while LDL-cholesterol and triglyceride levels were significantly increased by 21 percent and 50 percent, respectively. The total cholesterol level was not changed. CONCLUSION: High-dose IVIG treatment decreased the levels of a variety of proteins except immunoglobulins, and the increase of IgG after IVIG treatment was lower than expected. Our results suggest that a part of infused IVIG and plasma proteins, including etiologic proteins for Kawasaki disease, may be distributed to the extravascular compartments. The rapid improvement of symptoms induced by IVIG in Kawasaki disease might be explained by this mode of action of IVIG.

Anemia of Chronic Disease

Although anemia of chronic disease (ACD) is the most prevalent form of anemia next to iron deficiency anemia, its significance has been overridden by the dominant manifestation of the underlying diseases, i.e. chronic inflammation, infection, organ failure, or malignancy. As the treatment of ACD is being recognized to be important for the restoration of life quality, clinicians should be aware of how to detect, how to discriminate, and how to treat the disease. The key pathophysiology of ACD lies on the trapping of iron in the reticuloendothelial system by pro-inflammatory cytokines. The best treatment of ACD is the treatment of underlying disease per se, which is unfeasible in a substantial portion of the cases. Blood transfusion is occasionally harmful without altering the natural course of underlying disease. The benefit of erythropoietin (EPO) was already established in chronic renal disease. EPO has emerged as an important palliative measure for anemia in a variety of cancers. Augmented supplement of EPO may overcome the blunted response to physiologic EPO in anemia secondary to chronic infection or inflammation. Functional or absolute iron deficiency in ACD is manageable using EPO in conjunction with parenteral iron supplement. The iron deficiency in ACD can be identified by low ferritin value (2). Further studies are required for the elucidation of molecular pathogenesis, more accurate diagnosis and new treatment to mobilize trapped iron into active erythropoiesis. The judicious use of therapeutic options currently available can result in palliation of ACD in a majority of the patients, and every single clinician should be fully aware of the principles behind the palliative measures.