Changes In Multiple Organs Research Articles

Inhibition of Cerebral High-Mobility Group Box 1 Protein Attenuates Multiple Organ Damage and Improves T Cell-Mediated Immunity in Septic Rats.

Sepsis remains one of the leading causes of mortality in intensive care units, but there is a shortage of effective treatments. A dysregulated host immune response and multiple organ injury are major factors for the pathogenesis and progression of sepsis, which require specific mechanism and treatment. In the present study, we performed an intracerebroventricular (ICV) injection of BoxA, a specific antagonist of high-mobility group box 1 protein (HMGB1), in septic rats that were produced by cecal ligation and puncture surgery; we further assessed the functional changes of multiple organs and splenic T lymphocytes. We found that the inhibition of cerebral HMGB1 significantly alleviated multiple organ damage under septic exposure, including damage to the heart, liver, lungs, and kidneys; reversed the immune dysfunction of T cells; and increased the survival of septic rats. These data suggest that central HMGB1 might be a potential therapeutic target for septic challenge and that inhibition of brain HMGB1 can protect against multiple organ dysfunction induced by sepsis.

Histologic Changes In Recreational Drug Misuse.

Use of recreational drugs is associated with a number of histologic changes. These may be related to the method of administration or due to systemic effects of the drugs. This paper reviews the histopathological features seen following recreational drug use. With injection, there may be local effects from abscess formation and systemic effects may result in amyloidosis. Injections have been associated with necrotizing fasciitis, anthrax, and clostridial infections. Systemic effects include infective endocarditis, with the risk of embolization, and abscesses may be seen in organs in the absence of infective endocarditis. Viral complications of injection include hepatitis and human immunodeficiency virus (HIV) infection. Injecting crushed tablets can result in intravascular granulomata in the lungs. Smoking drugs is associated with intraalveolar changes, including blackand brown-pigmented macrophages in crack cocaine and cannabis smoking, respectively. Snorting may result in intraalveolar granulomata forming when crush tablets are used and there may be systemic granulomata. Stimulants are associated with cardiovascular and cerebrovascular pathology, including contraction band necrosis and myocardial fibrosis, as well as coronary artery dissection. Stimulants may cause hyperpyrexia and rhabdomyolysis, which may be associated with changes in multiple organs including myoglobin casts in the kidney. Opioids cause respiratory depression and this can be associated with inhalational pneumonia and hypoxia in other organs if there is resuscitation and a period of survival. Ketamine use has been associated with changes in the urothelium and the liver. This paper reviews histology changes that may be seen in drug-related deaths using illustrative cases.

Personalized epigenetic management of diabetes.

The novel genome-wide assays of epigenetic marks have resulted in a greater understanding of how genetics and the environment interact in the development and inheritance of diabetes. Chronic hyperglycemia induces epigenetic changes in multiple organs, contributing to diabetic complications. Specific epigenetic-modifying compounds have been developed to erase these modifications, possibly slowing down the onset of diabetes-related complications. The current review is an update of the previously published paper, describing the most recent advances in the epigenetics of diabetes.

Prediction and Subtyping of Hypertension from Pan-Tissue Transcriptomic and Genetic Analyses.

Hypertension (HT) is a complex systemic disease involving transcriptional changes in multiple organs. Here we systematically investigate the pan-tissue transcriptional and genetic landscape of HT spanning dozens of tissues in hundreds of individuals. We find that in several tissues, previously identified HT-linked genes are dysregulated and the gene expression profile is predictive of HT. Importantly, many expression quantitative trait loci (eQTL) SNPs associated with the population variance of the dysregulated genes are linked with blood pressure in an independent genome-wide association study, suggesting that the functional effect of HT-associated SNPs may be mediated through tissue-specific transcriptional dysregulation. Analyses of pan-tissue transcriptional dysregulation profile, as well as eQTL SNPs underlying the dysregulated genes, reveals substantial heterogeneity among the HT patients, revealing two broad groupings - a Diffused group where several tissues exhibit HT-associated molecular alterations and a Localized group where such alterations are localized to very few tissues. These two patient subgroups differ in several clinical phenotypes including respiratory, cerebrovascular, diabetes, and heart disease. These findings suggest that the Diffused and Localized subgroups may be driven by different molecular mechanisms and have different genetic underpinning.

Vitamin B12 deficiency among vegetarian and non-vegetarian diabetic population receiving prolonged Metformin based oral hypoglycemic agents therapy

Background: Diabetes is a group of metabolic disorder that share the phenotype of hyperglycemia. Over the period of time the metabolic dysregulation associated with diabetes mellitus causes secondary pathophysiological changes in multiple organs like heart, blood vessels, eyes, kidney and nerves resulting in various complications. However, a common potential interaction of metformin with vitamin B-12 is well documented but is poorly studied by the physicians who prescribe metformin to their diabetic patients. Since vitamin B-12 deficiency is common among vegan population as compared to population consuming food of animal origin (meat, fish and dairy products). But in this article, it has been studied that metformin cause vitamin B-12 deficiency even in non-vegetarian population. The aim of this study was to asses’ vitamin B12 deficiency among vegetarian and non-vegetarian diabetic population receiving prolonged Metformin based oral hypoglycaemic agents therapy. It was a cross sectional study done in Department of Medicine, UPUMS, Saifai, Etawah, Uttar Pradesh, India.Methods: Study done among patients of type 2 diabetes mellitus of age group 30-60 years on prolonged metformin based OHA therapy and having peripheral neuropathy were included in study. Data was analysed on SPSS Version 22.0 and p value obtained.Results: Statistical analysis of 93 patients included in study showed that vitamin B12 deficiency is common among the vegetarian (56.52%) and non-vegetarian (35.71%) population but the difference is not statistically significant (p value=0.29) which is more in favour of metformin associated vitamin B12 deficiency in non-vegetarian population.Conclusions: Vitamin B12 deficiency is common in diabetes patients on metformin based OHA therapy hence we recommend routine screening for Vitamin B12 deficiency in such diabetes patients.

Analysis of mortality in patients with severe community-acquired pneumonia on the background of influenza A (H1N1) pdm09

Aim. To analyze clinical and morphological features of lethal outcomes in influenza A (H1N1) pdm09. 
 Methods. The article provides an analysis of 21 cases of death from severe complicated influenza A (H1N1) pdm09. A clinical example is presented. The diagnosis of influenza A (H1N1) pdm09 was laboratory-confirmed by polymerase chain reaction in vivo in nasopharyngeal swab samples. The diagnosis of influenza A (H1N1) pdm09 was also confirmed posthumously by polymerase chain reaction with detection of influenza virus antigens in autopsy materials. 
 Results. The deceased were 25 to 63 years old, were admitted on day 5 to 8 from the beginning of the disease (in average, 6.4±0.6 days), among them 12 (57%) females and 9 (43%) males. The risk factors were overweight and obesity in 18 (85.7%) patients. Lethal outcome occurred as a result of acute respiratory failure and acute respiratory distress syndrome. Morphologically severe total involvement of trachea, lungs and bronchi with congestion of internal organs was detected. Clinical manifestations of acute respiratory failure and acute respiratory distress syndrome were morphologically associated with alveolar damage. In all cases of death diffuse alveolar damage and multiple organ changes were diagnosed. 
 Conclusion. Severe course of influenza A (H1N1) pdm09, complicated with community-acquired viral and bacterial pneumonia, was associated with the development of infectious-toxic shock; lethal outcome occured as a result of ARF acute respiratory failure and acute respiratory distress syndrome; severe total involvement of trachea, lungs and bronchi with congestion of internal organs was confirmed morphologically.

The Effects of Remifentanil on Expression of High Mobility Group Box 1 in Septic Rats.

High mobility group box 1 (HMGB1) is a pivotal mediator of sepsis progression. Remifentanil, an opioid agonist, has demonstrated anti-inflammatory effects in septic mice. However, it is not yet known whether remifentanil affects the expression of HMGB1. We investigated the effects of remifentanil on HMGB1 expression and the underlying mechanism in septic rats. Forty-eight male Sprague-Dawley rats were randomly divided into 3 groups; a sham group, a cecal ligation and puncture (CLP) group, and a CLP with remifentanil treatment (Remi) group. The rat model of CLP was used to examine plasma concentrations of proinflammatory cytokines, tissue HMGB1 mRNA and the activity of nuclear factor (NF)-κB in the liver, lungs, kidneys, and ileum. Pathologic changes and immunohistochemical staining of NF-κB in the liver, lungs, and kidneys tissue were observed. We found that remifentanil treatment suppressed the level of serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α 6 hours after CLP, and serum HMGB1 24 hours after CLP. HMGB1 mRNA levels and the activity of NF-κB in multiple organs decreased by remifentanil treatment 24 hours after CLP. Remifentanil treatment also attenuated nuclear expression of NF-κB in immunohistochemical staining and mitigated pathologic changes in multiple organs. Altogether, these results suggested that remifentanil inhibited expression of HMGB1 in vital organs and release of HMGB1 into plasma. The mechanism was related to the inhibitory effect of remifentanil on the release of proinflammatory cytokines and activation of NF-κB.

Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues.

Mice harbouring a dentin matrix protein 1 (Dmp1) promoter-driven human diphtheria toxin (DT) receptor (HDTR) transgene (Tg) have recently been used to attain targeted ablation of osteocytes by diphtheria toxin (DT) treatment in order to define osteocyte function. Use of these Tg mice has asserted mechano- and novel paracrine regulatory osteocyte functions. To explore osteocyte roles fully, we sought to confirm the selectivity of DT effects in these transgenic mice. However, our findings revealed incomplete DT-induced osteocyte ablation, prevalent HDTR misexpression, as well as more prominent histopathological DT-induced changes in multiple organs in Tg than in wild-type (WT) littermate mice. Mechanistic evidence for DT action, via prominent regulation of phosphorylation status of elongation factor-2 (EF-2), was also found in many non-skeletal tissues in Tg mice; indicative of direct “off-target” DT action. Finally, very rapid deterioration in health and welfare status in response to DT treatment was observed in these Tg when compared to WT control mice. Together, these data lead us to conclude that alternative models for osteocyte ablation should be sought and caution be exercised when drawing conclusions from experiments using these Tg mice alone.

Protective effects of levamisole, acetylsalicylic acid, and \u03b1-tocopherol against dioxin toxicity measured as the expression of AhR and COX-2 in a chicken embryo model

Polychlorinated dibenzo-p-dioxins and dibenzofurans (dioxins) are classed as persistent organic pollutants and have adverse effects on multiple functions within the body. Dioxins are known carcinogens, immunotoxins, and teratogens. Dioxins are transformed in vivo, and interactions between the products and the aryl hydrocarbon receptor (AhR) lead to the formation of proinflammatory and toxic metabolites. The aim of this study was to determine whether α-tocopherol (vitamin E), acetylsalicylic acid (ASA), and levamisole can decrease the amount of damage caused by dioxins. Fertile Hubbard Flex commercial line chicken eggs were injected with solutions containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or containing TCDD and the test compounds. The chicken embryos and organs were analyzed after 7 and 13 days. The levels at which AhR and cyclooxygenase-2 (COX-2) proteins (which are induced during inflammation) were expressed were evaluated by performing immunohistochemical analyses on embryos treated with TCDD alone or with TCDD and the test compounds. TCDD caused developmental disorders and increased AhR and COX-2 expression in the chicken embryo tissues. Vitamin E, levamisole, ASA, and ASA plus vitamin E inhibited AhR and COX-2 expression in embryos after 7 days and decreased AhR and COX-2 expression in embryos after 13 days. ASA, levamisole, and ASA plus vitamin E weakened the immune response and prevented multiple organ changes. Vitamin E was not fully protective against developmental changes in the embryos.

Antiplatelet strategies in elderly people: still a long way to go

Outcomes of patients with acute coronary syndrome undergoing percutaneous coronary intervention have been significantly improved with the potent P2Y12 receptor inhibitors prasugrel and ticagrelor. 1 Wiviott SD Braunwald E McCabe CH et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007; 357: 2001-2015 Crossref PubMed Scopus (5562) Google Scholar , 2 Wallentin L Becker RC Budaj A et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009; 361: 1045-1057 Crossref PubMed Scopus (5545) Google Scholar Elderly patients comprise a growing subset of the acute coronary syndrome population. This subset is characterised by multiple organ changes and various comorbidities, which altogether culminate in an increased risk of both ischaemic and bleeding complications after percutaneous coronary intervention. Platelet function testing has been established and validated to predict ischaemic and bleeding events in patients treated with percutaneous coronary intervention. 3 Aradi D Kirtane A Bonello L et al. Bleeding and stent thrombosis on P2Y12-inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J. 2015; 36: 1762-1771 Crossref PubMed Scopus (268) Google Scholar , 4 Tantry US Bonello L Aradi D et al. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol. 2013; 62: 2261-2273 Summary Full Text Full Text PDF PubMed Scopus (756) Google Scholar However, previous studies, 5 Collet JP Cuisset T Range G et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med. 2012; 367: 2100-2109 Crossref PubMed Scopus (759) Google Scholar , 6 Aradi D Storey RF Komocsi A et al. Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J. 2014; 35: 209-215 Crossref PubMed Scopus (213) Google Scholar enrolling mostly low-risk patients with little use of potent antiplatelet drugs, have been unable to show clinical superiority of strategies that implemented platelet function testing for treatment guidance. Nevertheless, elderly patients undergoing percutaneous coronary intervention represent a high-risk cohort that might derive clinical benefit from platelet function testing to monitor and adjust the level of platelet inhibition. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trialPlatelet function monitoring with treatment adjustment did not improve the clinical outcome of elderly patients treated with coronary stenting for an acute coronary syndrome. Platelet function testing is still being used in many centres and international guidelines still recommend platelet function testing in high-risk situations. Our study does not support this practice or these recommendations. Full-Text PDF

Fungal infection of cystic fibrosis patients - single center experience.

Cystic fibrosis (CF) is the most common monogenetic autosomal recessive disease in the human population. This systemic disease is characterized by changes in multiple organs, mainly in the lung tissue and digestive tract. More than 59% of CF patients become sensitized to fungal spores, mostly Aspergillus fumigatus. 5-15% of CF patients develop allergic bronchopulmonary aspergillosis. The aim of the study was to analyse the occurrence of yeast and filamentous fungi of the respiratory infections in CF patients and evaluation of drug resistance. Between 2006 and 2014, mycological evaluation of 42 patients hospitalized at the National Institute of Tuberculosis and Lung Diseases was carried out. 217 specimens from pulmonary tract were collected from 42 patients with cystic fibrosis. 205 (68%) strains of yeast and 96 (32%) filamentous fungi strains were cultured. The most common mould strain was A. fumigatus - 22,2% (67 species). All isolates of filamentous fungi were in vitro 100% susceptible to itraconazole, voriconazole, posaconazole and amphotericin B. A. fumigatus and C. albicans were the most common etiological agents of fungal respiratory pathogens associated with CF patients. A. fumigatus strains were in vitro 100% susceptible to azole and amphotericin B. Two strains of C. albicans and one strain of C. tropicalis were non-susceptible to azole (fluconazole, itraconazole and voriconazole). Scedosporium apiospermum was resistant to amphotericin B (MIC > 32 mg/l) and susceptible to voriconazole (MIC 0.094 mg/l).

Investigation of relative metabolic changes in the organs and plasma of rats exposed to X-ray radiation using HR-MAS (1)H NMR and solution (1)H NMR.

Excess exposure to ionizing radiation generates reactive oxygen species and increases the cellular inflammatory response by modifying various metabolic pathways. However, an investigation of metabolic perturbations and organ-specific responses based on the amount of radiation during the acute phase has not been conducted. In this study, high-resolution magic-angle-spinning (HR-MAS) NMR and solution NMR-based metabolic profiling were used to investigate dose-dependent metabolic changes in multiple organs and tissues--including the jejunum, spleen, liver, and plasma--of rats exposed to X-ray radiation. The organs, tissues, and blood samples were obtained 24, 48, and 72 h after exposure to low-dose (2 Gy) and high-dose (6 Gy) X-ray radiation and subjected to metabolite profiling and multivariate analyses. The results showed the time course of the metabolic responses, and many significant changes were detected in the high-dose compared with the low-dose group. Metabolites with antioxidant properties showed acute responses in the jejunum and spleen after radiation exposure. The levels of metabolites related to lipid and protein metabolism were decreased in the jejunum. In addition, amino acid levels increased consistently at all post-irradiation time points as a consequence of activated protein breakdown. Consistent with these changes, plasma levels of tricarboxylic acid cycle intermediate metabolites decreased. The liver did not appear to undergo remarkable metabolic changes after radiation exposure. These results may provide insight into the major metabolic perturbations and mechanisms of the biological systems in response to pathophysiological damage caused by X-ray radiation.

Ageing: Out with the old.

The selective elimination of cells that have adopted an irreversible, senescent state has now been shown to extend the lifespan of mice and to ameliorate some age-related disease processes. See Article p.184 Various tissues and organs accumulate senescent cells during normal ageing, but it is not known whether — or how — these cells influence health and lifespan. Jan van Deursen and colleagues show that when senescent cells accumulate during adulthood they are a negative influence on lifespan and promote age-dependent changes in multiple organs. Clearance of these cells delayed tumorigenesis and attenuated age-related deterioration of several organs without overt side effects. This finding suggests that therapeutic removal of senescent cells may be able to extend healthy lifespan.

Systemic Metabolic Responses of Broiler Chickens and Piglets to Acute T-2 Toxin Intravenous Exposure.

The aim of this study is to thoroughly investigate the toxicity mechanism of mycotoxin T-2 toxin and to further understand the endogenous metabolic alterations induced by T-2 toxin. To achieve this, a nuclear magnetic resonance (NMR)-based metabonomics approach was used to analyze the metabolic alterations induced by a single intravenous injection of T-2 toxin (0.5 mg/kg of body weight) in piglets and broiler chickens. A range of metabolites in the plasma, liver, kidney, and spleen of broiler chickens and plasma of piglets was changed following T-2 toxin injection. For example, a rapid increase of amino acids together with a significant reduction of glucose and lipid occurred in the plasma of broiler chickens and piglets following T-2 toxin treatment. A significant accumulation of amino acids and modulated nucleotides were detected in the liver, kidney, and spleen of T-2 toxin-treated broiler chickens. These data indicated that T-2 toxin caused endogenous metabolic changes in multiple organs and perturbed various metabolic pathways, including energy, amino acid, and nucleotide metabolism, as well as oxidative stress. We also observed elevated levels of tryptophan in the T-2 toxin-treated broiler chickens, which may explain the reported neurotoxic effects of T-2 toxin. These findings provide important information on the toxicity of T-2 toxin and demonstrate the power of the NMR-based metabonomics approach in exploring the toxicity mechanism of xenobiotics.

Drag-reducing polyethylene oxide improves microcirculation after hemorrhagic shock

BackgroundDespite resuscitation after trauma, microcirculatory abnormalities are known to persist in post-shock multiorgan dysfunction. The high-molecular weight polymer polyethylene oxide (PEO) (>106 Da), a classic drag-reducing polymer, can improve hemorrhagic shock (HS)–induced hemodynamic abnormalities in rats. Materials and methodsWe examined the effects of PEO on microcirculation and on changes in multiple organs after shock. After the spinotrapezius muscle was prepared, HS was induced in Sprague–Dawley rats. Drug administration (normal saline or PEO) was performed 2 h after shock followed by infusion of shed blood. ResultsThe velocity, blood flow, and functional capillary density in the shock + PEO group were significantly higher than those in the shock + normal saline group. Moreover, the kidney, liver, and lung function was improved, resulting in prolonged survival time. Our findings indicate that intravenous infusion of PEO can ameliorate shock-associated organ dysfunction and prolong survival time in severe HS, which may be a result of increased arteriolar blood velocity, blood flow, and functional capillary density. ConclusionsPEO could have potential clinical application in the treatment of shock-induced multiorgan dysfunction.

Inflammatory responses to neutral fat and fatty acids in multiple organs in a rat model of fat embolism syndrome

Fat embolism syndrome (FES) is a common complication of long bone fractures. FES is rare but with significant morbidity and occasional fatalities. Studies of animal models of FES are numerous; however, few studies compare inflammatory reactions in multiple organs. The present study investigated the effect of neutral fat and fatty acids, which cause changes in multiple organs and induce FES. Using rats we evaluated the ratio of lung-to-body weight and conducted histological analyses and quantitative analysis of inflammatory cytokine mRNAs in the lungs following intravenous administration of neutral fat or fatty acids. Neutral fat increased the ratio of lung-to-body weight, and neutral fat formed emboli in lung capillaries. The levels of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) in the lungs increased after injection of neutral fat and oleic acid. Analysis of the histologic changes revealed that the highest numbers of fat droplets, occluding the capillaries of the lungs, kidney, heart, and brain formed 12h after the injection of neutral fat and fat droplets gradually diminished 48h later. Fat droplets were not detected in any organs after the injection of oleic acid. IL-1β and TNF-α levels in the lungs were elevated 9–24h after the injection of neutral fat, although IL-6 levels peaked at 6h. After injection of oleic acid, peak levels of IL-1β, IL-6, and TNF-α were detected at 6h, and IL-6 again increased in all organs and plasma at 15h. Neutral fat, but not fatty acids, formed emboli in the capillaries of multiple organs. These findings suggest that neutral fat increased inflammatory cytokine levels by forming emboli in organ capillaries, particularly in the lungs, while oleic acid augmented inflammatory cytokine levels by stimulating endothelial cells of multiple organs.

Neuropathology of Natural Cytauxzoon felis Infection in Domestic Cats.

Cytauxzoonosis is a tick-borne disease of felids caused by the protozoan Cytauxzoon felis. This article characterizes the neuropathologic changes in 8 cases of natural C. felis infection in domestic cats with typical clinical signs and pathologic changes in multiple organs. Histologic changes in the brain included intravascular schizont-laden macrophages in leptomeningeal and parenchymal arterioles and venules. Small capillaries throughout the gray and white matter and choroid plexus also appeared occluded. Affected vessels were often surrounded by small to moderate numbers of lymphocytes and plasma cells and multiple areas of hemorrhage. Vasculitis and fibrin thrombi were occasionally present. Parenchymal changes consisted of variable degrees of vacuolation of the gray and white matter, with microgliosis, astrocytosis, astrogliosis, and multiple microhemorrhages. Multiple well-demarcated areas of necrosis observed in 4 cases were characterized by marked vacuolation of the gray or white matter, with necrotic neurons containing shrunken hypereosinophilic cytoplasm and pyknotic nuclei, nuclear debris, swollen axons, and scattered foamy macrophages. The changes in the brains of affected cats were attributed to vascular occlusion and secondary ischemia caused by the protozoal infection.

Systematic analysis of the associations between adverse drug reactions and pathways.

Adverse drug reactions (ADRs) are responsible for drug candidate failure during clinical trials. It is crucial to investigate biological pathways contributing to ADRs. Here, we applied a large-scale analysis to identify overrepresented ADR-pathway combinations through merging clinical phenotypic data, biological pathway data, and drug-target relations. Evaluation was performed by scientific literature review and defining a pathway-based ADR-ADR similarity measure. The results showed that our method is efficient for finding the associations between ADRs and pathways. To more systematically understand the mechanisms of ADRs, we constructed an ADR-pathway network and an ADR-ADR network. Through network analysis on biology and pharmacology, it was found that frequent ADRs were associated with more pathways than infrequent and rare ADRs. Moreover, environmental information processing pathways contributed most to the observed ADRs. Integrating the system organ class of ADRs, we found that most classes tended to interact with other classes instead of themselves. ADR classes were distributed promiscuously in all the ADR cliques. These results reflected that drug perturbation to a certain pathway can cause changes in multiple organs, rather than in one specific organ. Our work not only provides a global view of the associations between ADRs and pathways, but also is helpful to understand the mechanisms of ADRs.

Histological and biochemical studies on the effect of vitamin E on sodium fluoride induced lung toxicity in adult albino rats

Introduction Fluoride compounds are naturally present in soil, water, and food. Furthermore, fluoride in amounts exceeding the standard therapeutic dosage accumulates in hard and soft tissues, where it disturbs the metabolic processes and produces noticeable changes in multiple organs. Aim The study was designed to investigate the effects of sodium fluoride (NaF) on the lung of adult albino rats and the possible protective role of vitamin E on these changes. Materials and methods Twenty-six adult albino rats were divided into three groups: group I (control), group II receiving NaF alone (10 mg/kg body weight), and group III receiving the same NaF dose together with vitamin E supplementation (3 mg/day orally for 35 days). Tissue homogenates were collected for biochemical study, and the lung tissues were excised for histological, immunohistochemical, and biochemical studies. The results of biochemical and immunohistochemical studies were measured and statistically analyzed. Results Lung sections of rats treated with NaF showed congestion and injury in the endothelium of blood vessels, with hemorrhage and injury in the alveolar epithelium. Proliferation of pneumocytes type II and interstitial septal cells were seen. Thickening of interalveolar septum by cellular infiltration and red blood cells with subsequent decrease in the alveolar space was observed. Some area showed compensatory dilated alveolar ducts. A significant increase in the mean area% of cyclooxygenase-2-immunopositive cells was observed when compared with other groups. There was a significant decrease in the catalase activity and an increase in malondialdehyde concentration in group II. In vitamin E-treated group, most fields showed normal lung structure and some fields showed thickened interalveolar septa and dilated air spaces. Conclusion The use of vitamin E has a beneficial effect on the protection of lung against NaF-induced injury.

Effects of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis

To investigate the protective effects and mechanisms of action of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis (SAP). The rats were divided into sham-operated, model control, dexamethasone treated, and Salvia miltiorrhiza treated groups. At 3, 6, and 12 h after operation, the mortality rate of different groups, pathological changes, Bcl-2-associated X protein (Bax) and nuclear factor-κB (NF-κB) protein expression levels in multiple organs (the pancreas, liver, kidneys, and lungs), toll-like receptor 4 (TLR-4) protein levels (only in the liver), intercellular adhesion molecule 1 (ICAM-1) protein levels (only in the lung), and terminal deoxynucleotidy transferase mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining expression levels, as well as the serum contents of amylase, glutamate-pyruvate transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), and creatinine (CREA) were observed. The mortality rate of the dexamethasone treated group was significantly lower than that of the model control group (P<0.05). The pathological changes in multiple organs in the two treated groups were relieved to different degrees (P<0.05 and P<0.01, respectively), the expression levels of Bax and NF-κB proteins, and apoptotic indexes of multiple organs were reduced (P<0.05 and P<0.01, respectively). The contents of amylase, GPT, GOT, BUN, and CREA in the two treated groups were significantly lower than those in model control groups (P<0.05 and P<0.01, respectively). The expression level of ICAM-1 protein in the lungs (at 3 and 12 h) in the dexamethasone treated group was significantly lower than that in the Salvia miltiorrhiza treated group (P<0.05). The serum contents of CREA (at 12 h) and BUN (at 6 h) of the Salvia miltiorrhiza treated group were significantly lower than those in the dexamethasone treated group (P<0.05). Both dexamethasone and Salvia miltiorrhiza can reduce the inflammatory reaction, regulate apoptosis, and thus protect multiple organs of rats with SAP.