Time Course of Endotoxin-Induced Airways’ Inflammation in Healthy Subjects

Few data are available on the kinetic of the airways’ inflammation induced by inhaled endotoxin in a given subject. The purpose of this study was to evaluate in healthy subjects the time-related endotoxin-induced airways’ inflammation. The cells counts from the induced-sputum were evaluated before, 6 and 24 h, and 7 days after an exposure to 20 mcg inhaled endotoxin, in eight pre-selected volunteers. To avoid interference of the induced-sputum procedure on the response to endotoxin, each time-point was evaluated in randomized order at 2-weeks interval after three separate inhalations of endotoxin. A significant rise of the relative number of lymphocytes (p < 0.05) and polymorphonuclear neutrophils (PMN; p < 0.02) and of the absolute number of PMN (p < 0.05) occurring at 6 h, followed by an increase of the absolute number of the total viable cells (p < 0.01), macrophages (p < 0.001), neutrophils (p < 0.01), and lymphocytes (p < 0.05) at 24 h after endotoxin inhalation. The inflammatory response recovered totally after 7 days. In human beings, the inhalation of endotoxin induced a transient airway inflammation after 6 h, peaked at 24 h and recovered after 7 days. When repeated endotoxin inhalations are used as a model of inflammation, a wash-out period of at least 7 days should be applied between each exposure in each subject.     

Synthesis of pediculocidal and larvicidal silver nanoparticles by leaf extract from heartleaf moonseed plant, Tinospora cordifolia Miers

Insecticide resistance and inadequate attention to the application instructions of topical pediculicides are common reasons for treatment failure. Essential oils or plant extracts are good and safe alternatives due to their low toxicity to mammals and easy biodegradability. The present study was carried out to establish the pediculocidal and larvicidal activity of synthesized silver nanoparticles (AgNPs) using leaf aqueous extract of Tinospora cordifolia Miers (Menispermaceae) against the head louse Pediculus humanus capitis De Geer (Phthiraptera: Pediculidae) and fourth instar larvae of malaria vector, Anopheles subpictus Grassi and filariasis vector, Culex quinquefasciatus Say (Diptera: Culicidae). We reported the aqueous plant extract and synthesized AgNPs against head lice and vectors. Direct contact method was conducted to determine the potential of pediculocidal activity. The synthesized AgNPs characterized by UV–vis spectrum, scanning electron microscopy, Fourier transform infrared, and X-ray diffraction. Head lice and mosquito larvae were exposed to varying concentrations of aqueous extracts and synthesized AgNPs for 24 h. The results suggest that the optimal times for measuring mortality effects of synthesized AgNPs were 33% at 5 min, 67% at 15 min, and 100% after 1 h. The maximum activity was observed in the synthesized AgNPs against lice, A. subpictus and C. quinquefasciatus (LC₅₀ = 12.46, 6.43 and 6.96 mg/L; r ² = 0.978, 0.773 and 0.828), respectively. The findings revealed that synthesized AgNPs possess excellent anti-lice and mosquito larvicidal activity. These results suggest that the green synthesis of AgNPs have the potential to be used as an ideal ecofriendly approach for the control of head lice and vectors.     

Haematological and clinical chemistry findings associated with sub-acute contamination of drinking water with varied low percentages of used engine oil

This study evaluated the haematology and clinical chemistry profile of rats given drinking water contaminated with varied low percentages of used engine oil (UEO) for a period of 21 days. Fifty female albino rats of 6–7 weeks of age were used for the study. They were divided into five groups (A–E) and given water contaminated with 5%, 1%, 0.1%, 0.01% and 0% vol/vol. of UEO respectively as the only source of drinking water for 21 days. The group E given uncontaminated water (0% contamination) served as the control. The haematological parameters and clinical chemistry profile of the rats was comprehensively evaluated after the 21 days of administration of the group-specific waters. Results showed that contamination of water with up to 5% UEO led to no significant effects (p > 0.05) on all the haematological indices and on the levels of serum alanine amino transferase, aspartate amino transferase, albumin, creatinine and calcium, blood urea nitrogen and fasting blood glucose level, feed consumption and body weight. However, the rat group given water contaminated with 5% UEO had a significantly increased serum alkaline phosphatase (AP) (p < 0.01), total bilirubin (p < 0.05) and cholesterol (p < 0.01), and a significantly decreased serum total protein and globulin (p < 0.01), and water consumption (p < 0.05). The rat group given water contaminated with 1% UEO had a significantly increased serum AP (p < 0.01), total bilirubin (p < 0.05) and cholesterol (p < 0.01), and a significantly decreased water consumption (p < 0.05), while the rat group given water contaminated with 0.1% UEO had a significantly elevated (p < 0.01) serum AP. It was concluded that sub-acute contamination of drinking water of rats with up to 5% UEO led to hepato-biliary disorders and adverse effects on hepatic secretion and excretion, including diminution of serum protein and globulin levels and elevation of serum cholesterol levels, but did not lead to any significant effects on haematology, hepatocellular integrity, kidney/renal function, pancreatic function and body weight.     

Exenatide enhances kaliuresis under conditions of hyperkalemia

Experiments on Wistar rats showed that exenatide (0.015–0.5 nmol per 100 g body weight) somewhat increased renal excretion of potassium from 7 ± 1 to 16 ± 1 μmol/h/100 g body weight (p < 0.05) in animals with normal serum concentration of glucose (4.6 ± 0.4 mM) and potassium (4.3 ± 0.1 mM). Exenatide dramatically enhanced excretion of potassium under conditions of hyperkalemia (11.4 ± 0.4 mM) produced by intraperitoneal injection of 1.25% KCl solution (5 ml per 100 g body weight). During the fi rst postinjection hour, potassium excretion increased 2-fold and attained 97 ± 11 μmol/h/100 g body weight in comparison with potassium load alone (47 ± 9 μmol/h/100 g body weight, p < 0.05). The data attest to a possible role of peptide regulators in normalization of potassium balance via renal mechanisms.     

Bacterial LPS Mediated Acute Inflammation-induced Spermatogenic Failure in Rats: Role of Stress Response Proteins and Mitochondrial Dysfunction

Bacterial Lipopolysaccharide (LPS) induced inflammation is implicated in the infection associated testicular tissue damage. Earlier, using a LPS induced acute endotoxemic rat model, we have shown the involvement of inflammation-induced oxidative stress in the impaired steroidogenesis and spermatogenesis. In the present study, we report a significant induction (more than 2-fold) of stress response proteins HSP-60, HMGB-1 and 2 in the testes, as early as 6 h after LPS injection with a later decrease. This induction of acute stress is closely followed by a significant reduction (74%) in Bcl2/Bax ratio along with leakage of cytochrome c (3 fold increase, p < 0.05) from mitochondria and increased caspase-3 activity levels (2.9 fold, p < 0.05) at 12 h and 24 h post LPS injection respectively. Further studies on PARP cleavage revealed a pattern similar to necrotic death during early periods (3 h to 24 h) and apoptosis at later periods (24 h to 72 h) after LPS treatment. In conclusion, the present study shows the involvement of stress response proteins and mitochondrial dysfunction in LPS-induced germ cell death in male rats.     

Hepatoprotective Effect of Infliximab,an Anti-TNF-α Agent,on Carbon Tetrachloride-Induced Hepatic Fibrosis

To assess the effect of infliximab, an anti-tumor necrosis factor (TNF)-α agent, on the carbon tetrachloride (CCl₄)-induced hepatic fibrosis in rats. Rats were randomized into three groups (n = 9). The control group received only intraperitoneal (i.p.) olive oil. Hepatic fibrosis was induced by repeated i.p. injections of 1.5 ml/kg CCl₄ (1:3 mixture with olive oil) for 5 weeks in the remaining two groups which were also injected subcutaneous saline or 2 mg/kg infliximab. Infliximab reduced the levels of aspartate aminotransferase and alanine aminotransferase (p < 0.05 for both). The scores of hepatic necrosis, inflammation and fibrosis, and expression of α-smooth muscle actin were lower in the infliximab-treated group than the CCI₄-treated group (p < 0.01, p < 0.001, p < 0.01, p < 0.001, respectively). However, there was no significant difference in terms of liver tissue and plasma malondialdehyde, and serum TNF-α levels, while infliximab relatively reduced the level of transforming growth factor-β₁ (373.0 ± 153.1 vs. 280.8 ± 127.1 pg/ml). Treatment with infliximab attenuated the necro-inflammation and fibrogenesis in the CCI₄-induced hepatic fibrosis, and thus it might be effective as a therapeutic anti-fibrotic agent.     

Muscle endurance and mitochondrial function after chronic normobaric hypoxia: contrast of respiratory and limb muscles

Skeletal muscle adaptation to chronic hypoxia includes loss of oxidative capacity and decrease in fiber size. However, the diaphragm may adapt differently since its activity increases in response to hypoxia. Thus, we hypothesized that chronic hypoxia would not affect endurance, mitochondrial function, or fiber size in the mouse diaphragm. Adult male mice were kept in normoxia (control) or hypoxia (hypoxia, FIO₂ = 10%) for 4 weeks. After that time, muscles were collected for histological, biochemical, and functional analyses. Hypoxia soleus muscles fatigued faster (fatigue index higher in control, 21.5 ± 2.6% vs. 13.4 ± 2.4%, p < 0.05), but there was no difference between control and hypoxia diaphragm bundles. Mean fiber cross-sectional area was unchanged in hypoxia limb muscles, but it was 25% smaller in diaphragm (p < 0.001). Ratio of capillary length contact to fiber perimeter was significantly higher in hypoxia diaphragm (28.6 ± 1.2 vs. 49.3 ± 1.4, control and hypoxia, p < 0.001). Mitochondrial respiration rates in hypoxia limb muscles were lower: state 2 decreased 19%, state 3 31%, and state 4 18% vs. control, p < 0.05 for all comparisons. There were similar changes in hypoxia diaphragm: state 3 decreased 29% and state 4 17%, p < 0.05. After 4 weeks of hypoxia, limb muscle mitochondria had lower content of complex IV (cytochrome c oxidase), while diaphragm mitochondria had higher content of complexes IV and V (F ₁/F ₀ ATP synthase) and less uncoupling protein 3 (UCP-3). These data demonstrate that diaphragm retains its endurance during chronic hypoxia, apparently due to a combination of morphometric changes and optimization of mitochondrial energy production.     

Increased Anxiety and Depression in Danish Cardiac Patients with a Type D personality: Cross-Validation of the Type D Scale (DS14)

Background  Type D personality is an emerging risk factor in cardiovascular disease. We examined the psychometric properties of the Danish version of the Type D Scale (DS14) and the impact of Type D on anxiety and depression in cardiac patients. Method  Cardiac patients (n = 707) completed the DS14, the Hospital Anxiety and Depression Scale, and the Eysenck Personality Questionnaire. A subgroup (n = 318) also completed the DS14 at 3 or 12 weeks. Results  The two-factor structure of the DS14 was confirmed; the subscales negative affectivity and social inhibition were shown to be valid, internally consistent (Cronbach’s α = 0.87/0.91; mean inter-item correlations = 0.49/0.59), and stable over 3 and 12 weeks (r = 0.85/0.78; 0.83/0.79; ps < 0.01). Type D was an independent associate of anxiety (β, 0.49; p < 0.01) and depression (β, 0.47; p < 0.01) in univariable linear regression analysis and remained a significant independent associate of anxiety (β, 0.26; p < 0.01) and depression (β, 0.17; p < 0.01) in adjusted analyses. Conclusions  The Danish DS14 was shown to be a valid and reliable measure associated with increased symptoms of anxiety and depression independent of socio-demographic and clinical risk factors. The DS14 may be used in research and clinical practice to identify high-risk patients.     

Environmental monitoring of ivermectin excreted in spring climatic conditions by treated cattle on dung fauna and degradation of faeces on pasture

The effect of ivermectin excreted in faeces of cattle treated in late winter on the arthropods and the degradation of faeces on pasture were evaluated. Four calves of similar age and weight were allocated to two groups, one group was treated subcutaneously with ivermectin and the other group remained as untreated control. From faeces collected from both groups at 3, 7, 14, 21 and 28 days post-treatment (dpt), three faecal pats of 1 kg each were made and deposited on a mixed paddock. One quarter of each faecal pat was removed at 10, 20, 30 and 60 days postdeposition (dpd) to determine the concentration of ivermectin, the organic matter content, and to collect colonising dung arthropods. Concentrations at days 3 and 7 pt were significantly higher than at the other dpt (p < 0.05). The highest ivermectin concentrations were found in samples from 3 dpt (p < 0.05). The organic matter percentage was not significantly different between treatments. An edaphic fauna characterised the colonisation of the faeces by organisms. Although arthropods’ abundance differences were not significant except for the 28 dpt at 30 dpd (p < 0.0003), fewer organisms were collected from the ivermectin group at all times.     

Morphometric changes, biochemical values, and kidney morphology of male West African Dwarf goats exposed to 2,4-dichlorophenoxyacetic acid (2,4-D)

This study investigated the morphometric changes, biochemical parameters, and kidney morphology of male West African Dwarf goats exposed to graded levels of 2,4-dichlorophenoxyacetic acid (2,4-D). Four groups of five goats were used for this experiment. Goats in three of the groups were exposed to oral administration of 2,4-D as follows: group A, low dose (75 mg/kg body weight); group B, medium dose (100 mg/kg body weight); and group C, high dose (125 mg/kg body weight); every 72 h for a period of 112 days. The group D goats served as the control and received no 2,4-D treatment. Morphometric changes, biochemical parameters, and histomorphological features of the kidney of goats exposed to 2,4-D were compared with control goats. Exposing male goats to 2,4-D treatment led to reduction in mean body weights (p < 0.05), mean blood glucose (p < 0.05), and mean total serum protein (p < 0.05) concentrations. The histomorphology of the kidney sections of the 2,4-D-treated goats was that of subacute to chronic exudative glomerulonephritis; and the severity of lesions increased with higher 2,4-D concentration. It was concluded that exposing male West African Dwarf goats to varied concentrations of 2,4-D herbicide resulted in reduction in weight gain, changes in blood glucose and total serum protein concentrations, as well as glomerular, tubular, and interstitial lesions in the kidney.     

Downregulated parafibromin expression is a promising marker for pathogenesis, invasion, metastasis and prognosis of gastric carcinomas

Parafibromin is a protein encoded by the hyperparathyroidism 2 oncosuppressor gene and its downregulated expression is involved in pathogenesis of parathyroid carcinomas. To clarify the roles of parafibromin expression in tumourigenesis and progression of gastric carcinomas, it was examined by immunohistochemistry (IHC) on tissue microarray containing gastric carcinomas (n = 508), adenomas (n = 45) and gastritis (n = 49) with a comparison of its expression with clinicopathological parametres of carcinomas. Gastric carcinoma cell lines (MKN28, AGS, MKN45, KATO-III and HGC-27) were studied for parafibromin expression by IHC and western blot. Parafibromin expression was localised in the nucleus of gastric epithelial cells, adenoma, carcinoma cells and cell lines. Its expression was gradually decreased from gastritis to gastric carcinoma, through gastric adenomas (p < 0.05) and inversely correlated with tumour size, depth of invasion, lymphatic invasion, lymph node metastasis and Union Internationale Contre le Cancer (UICC) staging (p < 0.05) but not with sex or venous invasion (p > 0.05). Parafibromin was strongly expressed in older carcinoma patients compared with younger ones (p < 0.05). There was stronger positivity of parafibromin in intestinal-type than diffuse-type carcinomas (p < 0.05). Univariate analysis indicated cumulative survival rate of patients with positive parafibromin expression to be higher than without its expression (p < 0.05). Multivariate analysis showed that age, tumour size, depth of invasion, lymphatic invasion, lymph node metastasis, UICC staging and Lauren’s classification but not sex, venous invasion or parafibromin expression were independent prognostic factors for carcinomas(p < 0.05). Downregulated parafibromin expression possibly contributed to pathogenesis, growth, invasion and metastasis of gastric carcinomas. It was considered as a promising marker to indicate the aggressive behaviours and prognosis of gastric carcinomas.     

Effect of xylazine–ketamine–diazepam anesthesia on certain clinical and arterial blood gas parameters in sheep and goats

This study was conducted to evaluate the effect of xylazine–ketamine–diazepam anesthesia on heart rate, respiration rate, rectal temperature, rumen motility, peripheral blood pH, PaO2, and PaCO2 in adult female nonpregnant Awassi sheep and adult female nonpregnant Damascus goats. Anesthesia was induced using 0.1 mg/kg, 5 mg/kg, and 0.25 mg/kg xylazine, ketamine, and diazepam respectively as a single intravenous injection. The heart rate, respiration rate, rectal temperature, rumen motility, peripheral arterial blood pH, PaO2, and PaCO2 were evaluated 15 min before and at 15, 30, and 60 min during anesthesia. In sheep, the heart rate, rumen motility, and PaO2 were decreased significantly (P < 0.05) at 15, 30, and 60 min following anesthesia. The respiration rate and rectal temperature and blood pH were decreased significantly (P < 0.05) at 30 and 60 min. The peripheral PaCO2 was increased significantly (P < 0.05) at 15 and 30 min. In goats, the heart rate and rumen motility were decreased significantly (P < 0.05) at 15, 30, and 60 min while the respiration rate was decreased only significantly (P < 0.05) at 60 min. Rectal temperature was decreased significantly (P < 0.05) at 30 and 60 min. The blood pH was decreased significantly (P < 0.05) at 15 and 30 min. PaO2 was only significantly (P < 0.05) decreased at 15 min while PaCO2 was increased significantly (P < 0.05) at 15 and 30 min.     

Increased type IIA secretory phospholipase A2 expression contributes to oxidative stress in end-stage renal disease

End-stage renal disease (ESRD) patients exhibit increased in vivo oxidative stress conceivably contributing to cardiovascular mortality. The type IIA secretory phospholipase A₂ (sPLA₂) has proatherogenic activity. We explored the hypothesis that sPLA₂ contributes to oxidative stress generation and endothelial dysfunction in ESRD patients and transgenic (tg) mice. Patients with ESRD had increased in vivo oxidative stress as assessed by plasma isoprostane levels (p < 0.001). Active sPLA₂ in plasma was substantially increased compared with healthy controls (1,156 ± 65 versus 184 ± 5 ng/dL, p < 0.001) and correlated with plasma isoprostanes (r = 0.61, p < 0.001). Correspondingly, human sPLA₂ tg mice display increased generation of reactive oxygen species within aortic vascular smooth muscle cells, leading to severe endothelial dysfunction (maximal vasodilation in response to 10 μmol/L acetylcholine, sPLA₂ 36 ± 8%, controls 80 ± 2% of phenylephrine-induced vasoconstriction). Increased vascular oxidative stress in sPLA₂ tg mice is dependent on the induction of vascular cyclooxygenase (COX)2 expression. Conversely, ESRD patients show increased formation of COX2-derived prostaglandins (p < 0.05) correlated with plasma sPLA₂ (r = 0.71, p < 0.05). Our data indicate that increased expression of sPLA₂ might represent a novel causative risk factor contributing to the increased cardiovascular disease morbidity and mortality in ESRD.     

Hepatoprotective activity of <Emphasis Type="Italic">Uvaria chamae</Emphasis> root bark methanol extract against acetaminophen-induced liver lesions in rats

The hepatoprotective activity of Uvaria chamae P. Beav (Annonaceae) methanol root bark extracts were tested in vivo and in vitro. The plant material was defatted with n-hexane and 70% methanol, respectively. The methanol extract was recovered in a 6.13% w/w yield. An oral administration of the methanol extract (60 mg/kg) significantly reduced (p < 0.05) pentobarbitone-induced sleep in rats poisoned with acetaminophen. In this model, a protection of 92% against the cytotoxicity of acetaminophen is obtained by pretreatment with the methanol extract as compared to a protection of 89.6% when the animals were pretreated with silibinin. The n-hexane extract was without a significant hepatoprotective effect in this model. Intraperitoneal injection of the methanol extract into rats showed no significant effect on pentobarbitone-induced hypnosis. The elevation of serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, alkaline phosphatase, and urea induced by paracetamol intoxication in rats was also significantly attenuated (p < 0.05) by the methanol extract. The methanol extract did not influence the concentration of microsomal proteins in the serum. This in vivo efficacy was substantiated by significant hepatoprotection on acetaminophen (AA)-induced hepatotoxicity in isolated rat hepatocytes. The methanol extract, at a dose of 1 mg/ml, remarkably (p < 0.05) reduced the leakage of lactate dehydrogenase in primary cultured rat hepatocytes and showed a significant effect on lipid peroxidation. The AA-induced elevation of the lipid peroxidation in rats was significantly (p < 0.05) decreased in the presence of U. chamae root bark methanol extract. A protection of 56% against the tert-butyl hydroperoxide-induced lipid peroxidation in rats was obtained by pretreatment with the methanol extract. The methanol extract also showed a significant antioxidant effect.     

Serodiagnosis of experimental sparganum infections of mice and human sparganosis by ELISA using ES antigens of Spirometra mansoni spargana

We conducted a study of serodiagnosis of experimental sparganum infections of mice and human sparganosis by enzyme-linked immunosorbent assay (ELISA) using excretory–secretory (ES) antigens of Spirometra mansoni spargana and compared the sensitivity and specificity of crude and ES antigens for detecting the specific anti-sparganum IgG antibodies. By crude antigen ELISA and ES antigen ELISA, anti-sparganum IgG was detected in all of 30 serum samples of the infected mice; no cross-reactions were observed in serum samples of the mice infected with Trichinella spiralis, Schistosoma japanicum, Toxoplasma gondii, and normal mice. Anti-sparganum IgG was detected by ES antigen ELISA in sera of mice infected with one, two, four, six, and eight spargana at 3 weeks post-infection (wpi), with a detection rate of 100%, and lasted to 18 wpi when the experiment was ended. The difference in anti-sparganum antibody levels among five groups of the infected mice was statistically significant (F = 245.296, p < 0.05); the antibody levels were correlated with infecting doses of spargana (r = 0.323, p < 0.05). The sensitivity of both ELISA in detecting the serum samples of patients with sparganosis was 100% (20/20), but 96.72% (59/61) of specificity of ES antigen ELISA in detecting serum samples of patients with cysticercosis, echinococcosis, paragonimiosis, clonorchiosis, and schistosomiasis, and healthy persons was significantly greater than 72.13% (44/61) of crude antigen ELISA (χ ² = 14.027, p < 0.05). Our finding indicates that ELISA using ES antigens of S. mansoni spargana may be applied to the specific early serodiagnosis of sparganosis.     

Vancomycin MIC creep in MRSA blood culture isolates from Germany: a regional problem?

The aim of this study was to assess the vancomycin MIC distribution for MRSA blood culture isolates over a period of six years in Germany. The study examined 287 MRSA isolates from blood cultures collected at several hospitals in two German cities between 2004 and 2009. The vancomycin MIC was determined by Etest. Genotypic features of the MRSA strains with vancomycin MIC ≥ 1 mg/L were determined by semiautomated repetitive-sequence-based polymerase chain reaction. The range of vancomycin MIC as determined by Etest was 0.25 to 2.0 mg/L. The geometric mean MIC increased by 1.34-fold in city A over the study period (p < 0.05), but there was no meaningful change in city B (a 1.09-fold increase, p > 0.05). Furthermore, in city A a shift in vancomycin MICs occurred as an increase in the percentage of isolates with MIC ≥ 1 mg/L from period one (2004–2006) to period two (2007–2009) (p < 0.0001). Typing results showed that in city A a single clone was predominant (55% of the creep isolates). In this study, the creep phenomenon seems to be a regional problem. We suggest that all hospitals should monitor their local status of elevated vancomycin MICs in invasive MRSA isolates.     

Increased IgG Antibody-Induced Cytotoxicity Against Airway Epithelial Cells in Patients with Nonallergic Asthma

Background  IgG autoantibodies to airway epithelial cell proteins have been detected in patients with nonallergic asthma. Objective and Methods  To evaluate the functional significance of these autoantibodies, we examined the presence of IgG antibody-induced cytotoxicity against airway epithelial cells (A549) by the microcytotoxicity assay using IgG antibodies purified from patients with nonallergic asthma. Results  IgG antibody-induced cytotoxicity (expressed as percent cell lysis) was significantly increased in nine patients with nonallergic asthma (mean ± standard deviation; 30.6 ± 7.3%) as compared with eight healthy controls (13.9 ± 5.1%) and nine patients with allergic asthma (20.3 ± 10.4%; p < 0.05). In addition, IgG antibody-induced cytotoxicity was significantly inhibited when IgG antibodies from patients with nonallergic asthma were pre-incubated with recombinant human airway epithelial cell autoantigens (cytokeratin 18 or alpha-enolase proteins; p < 0.05). Conclusion  These results suggest a possible involvement of IgG autoantibody-induced cytotoxicity against airway epithelial cells in the pathogenesis of nonallergic asthma.     

Spleen morphology and hematological changes in rats following withdrawal of Nigerian Qua Iboe Brent crude oil

Possible amelioration of splenic damage and hematological changes in Nigerian Qua Iboe Brent crude oil-exposed rats following its withdrawal was investigated. A total of 56 male albino rats weighing between 200–250 g were used for this study. The rats received oral administration of 165 mg/kg body weight (low-dose), 330 mg/kg body weight (medium-dose) and 660 mg/kg body weight (high-dose) of Nigerian Quo Iboe Brent crude oil every 48 h for 28 days. Later, the crude oil was withdrawn from some rats for a period of 8 weeks. Hematological parameters and spleen morphology of rats that received crude oil and the rats from which the crude oil was withdrawn were compared with the controls that did not receive crude oil treatment. Administration of Nigerian Qua Iboe Brent crude oil significantly (p < 0.05) reduced the PCV levels in low-dose, low-dose crude oil-withdrawn, medium-dose crude oil-withdrawn, high-dose, and high-dose crude oil-withdrawn groups of rats. The EC was also reduced significantly (p < 0.05) in the medium- and high-dose groups of rats. In the same manner, TWBC was significantly (p < 0.05) reduced in the medium-dose crude oil-withdrawn, high-dose, and high-dose crude oil-withdrawn rats. It was only at low-dose level, after 8 weeks of crude oil withdrawal that there was a reduction in splenic weight. Splenic section (histopathology) of rats exposed to different doses of crude oil over 28-day period showed reticuloendothelial hyperpasia of the red pulp and variable degree of haemosiderin deposits. These changes were not completely ameliorated after 8 weeks of crude oil withdrawal. This study has shown that withdrawal of Nigerian Qua Iboe Brent crude oil from exposed rats did not reverse the splenic damage and the haematologic changes associated with this environmental pollutant.     

Mixed-type gastric carcinomas exhibit more aggressive features and indicate the histogenesis of carcinomas

To investigate the pathobiological behaviors of gastric mixed-type (MT) carcinomas and gastric carcinogenesis, the clinicopathological characteristics of MT carcinomas were analyzed and compared with intestinal-type (IT) and diffuse-type (DT) carcinomas. The expression of Ki-67, caspase-3, p53, fragile histine triad (FHIT), maspin, extracellular matrix metalloproteinase inducer (EMMPRIN), vascular growth factor (VEGF), MUC-2, 4, 5AC and 6, CD44, E-cadherin, β-catenin, and phosphorylated glycogen synthase kinase 3β-ser⁹ (P-GSK3β-ser⁹) was examined on tissue microarrays using immunohistochemistry. It was found that MT carcinomas exhibited large size, deep invasion, frequent local invasion, and lymph node metastasis in comparison with IT and DT carcinomas (p < 0.05). All the markers except MUC-5AC showed higher expression in IT than DT carcinomas (p < 0.05). The expression of maspin, EMMPRIN, VEGF, MUC-4, and membrane E-cadherin was stronger in MT intestinal than diffuse component (p < 0.05). Immunoreactivities to Ki-67, EMMPRIN, and VEGF were weaker in IT carcinoma than in the MT intestinal portion (p < 0.05), while the opposite was true for CD44, MUC-2, and MUC-6 (p < 0.05). The MT diffuse component displayed a higher expression of FHIT, VEGF, and P-GSK3β-ser⁹ than DT carcinoma (p < 0.05). The accumulative survival rate of the IT carcinoma patients was higher than the other types (p < 0.05). The invasive depth, venous invasion, lymph node, peritoneal or liver metastasis, and Lauren's classification were independent prognostic factors for gastric carcinomas (p < 0.05). These findings suggested that MT carcinomas were also indicated to be more aggressive than IT and DT carcinomas. Significant differences were observed in the proliferation, apoptosis, angiogenesis, mucin secretion, and cell adhesion between IT and DT carcinomas, whereas only a few of these characteristics showed differences between the MT intestinal and diffuse parts, thus suggesting that both the MT components might originate from the stem cells with similar genetic traits, but follow different histogenic pathways.     

Overexpression of carbonic anhydrase IX (CAIX) is an independent unfavorable prognostic marker in endometrioid ovarian cancer

Carbonic anhydrase IX (CAIX) is a strictly membranous expressed metalloenzyme involved in cell adhesion, pH homeostasis, and cancer progression. This study was designed to assess the role of CAIX in primary ovarian cancer. Two hundred five well-characterized primary ovarian carcinomas were analyzed on a tissue microarray. CAIX expression was determined by immunohistochemistry using a four-step scoring system. Moderate and strong membranous CAIX expression was found in 37 out of 205 (18%) of all assessable ovarian cancer specimens. High levels of CAIX expression were related to mucinous and endometrioid phenotype of ovarian carcinomas (p < 0.05). There was no association between CAIX overexpression and tumor stage, grading, and mitotic count of ovarian carcinomas (p > 0.05). In univariate Cox regression analysis, advanced tumor stage (p < 0.01), high tumor grade (p = 0.017), high mitotic count (p = 0.025), and high CAIX expression levels (p = 0.031) were correlated to shorter overall patient survival. High pT stage (p = 0.036) and CAIX overexpression were connected to poor clinical outcome in endometrioid ovarian carcinomas. Multivariate Cox regression hazard analysis comprising tumor stage, tumor grade, mitotic count, and CAIX expression revealed pT2/3 stage and CAIX overexpression (scores 2 and 3) as independent prognostic markers in ovarian cancer (p < 0.01, each) as well as in the subgroup of endometrioid carcinomas (p < 0.05, each). In conclusion, CAIX is overexpressed in a substantial proportion of mucinous and endometrioid ovarian carcinomas and connected to poor patient outcome. Our data support the potential therapeutic benefit of newly developed targeting antibodies in advanced ovarian cancer.