Marked Pathological Changes Research Articles

Chinese medicinal formula, Qinggan Huoxue Recipe protects rats from alcoholic liver disease via the lipopolysaccharide-Kupffer cell signal conduction pathway

The Chinese medicinal formula, Qinggan (QG) Huoxue (HX) Recipe (R) exerts a range of pharmacological effects, including reversible steatosis, decreased levels of inflammatory cytokines and lipid peroxidation resistance. The aim of the present study was to determine the specific mechanisms of QGHXR hepatoprotection through the lipopolysaccharide-Kupffer cell (LPS-KC) signal conduction pathway in rats with alcoholic liver disease (ALD). ALD rats were exposed to the compound factors, QGR and HXR. Hematoxylin and eosin staining was conducted to evaluate the pathological changes in the liver following QGHXR treatment and an enzyme-linked immunosorbent assay was performed to measure the content of tumor necrosis factor (TNF)-α in the plasma. Immunohistochemical staining was conducted to examine the expression of cell differentiation antigen (CD) 68 and 14. In addition, western blot analysis and reverse transcription-polymerase chain reaction were used to measure the expression of Toll-like receptor 4 (TLR4), phosphorylated-extracellular regulated protein kinases (p-ERK), nuclear factor (NF)-κB, CD14 and TNF-α. Following stimulation with the compound factors, the rats exhibited increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, as well as marked pathological changes. Furthermore, the related molecules in the LPS-KC pathway were upregulated and QGHXR was identified to be effective in the LPS-KC signal conduction pathway in the ALD rats. QGHXR was superior to QGR and HXR in reducing the serum ALT and AST levels, regulating CD14, TLR4, NF-κB, ERK and TNF-α as well as improving the pathological changes. The results indicated that QGHXR therapy may provide a novel strategy for treating ALD via regulation of the related molecules in the LPS-KC signaling pathway.

Strongyloidiasis hyperinfection syndrome treatment with ivermectin: in-vitro and in-vivo studies

Background Strongyloides stercoralis is an intestinal nematode that usually causes asymptomatic infection in immunocompetent individuals and reverts to life-threatening hyperinfection in immunocompromised individuals. Objective The aim of the study was to evaluate the effect of ivermectin (IVM) treatment on S. stercoralis larvae in-vitro cultured forms. In-vivo evaluation was performed by assessment of parasitological, histopathological, and ultrastructural changes in the lungs of mice with Strongyloides hyperinfection syndrome before and after treatment with IVM. Materials and methods S. stercoralis larvae were collected from agar plates cultures of positive stool samples from different areas in Menuofyia Governorate. The in-vitro study involved the examination of S. stercoralis larvae grown in agar plates (APC) after exposure for 2 h to IVM (15 μl/ml) by scanning electron microscope (SEM) and after 24 h for larval motility. In-vivo study involved 96 mice that were divided into four groups (24 mice in each). Group GI was immunosuppressed by dexamethasone and infected with S. stercoralis larvae; GII was immunosuppressed then infected and treated by IVM (0.5 mg/kg); GIII was infected with S. stercoralis larvae; and GIV was infected and treated by IVM. Fecal larval output was carried out on 1 st , 6 th , 11 th , and 13 th days postinfection (dpi); histopathological examination of the lung was conducted on 2 nd , 7 th , 12 th , and 14 th dpi; and lung ultrastructure study by transmission electron microscopy (TEM) was performed on 7 th and 14 th dpi. Results IVM caused severe destruction of S. stercoralis larvae detected by SEM after 2 h and resulted in their death after 24 h. In-vivo results recorded significant decrease in fecal larval output in the treated groups (GII and GIV) and in GIII in comparison with GI. The latter showed significant continuous increase in fecal larval output throughout the period of study. Histopathological and ultrastructural results showed marked pathological changes in GI that were still evident until the last day of the study. IVM induced mild improvement in lung tissues in GII in comparison with GIV. The latter showed obvious improvement with great preservation of lung tissue. In GIII, mild pathological effect of infection was still evident by the end of study. Conclusion Dexamethasone-immunosuppressed mice infected by S. stercoralis showed intestinal and pulmonary hyperinfection. IVM showed significant improvement of all parameters studied mainly in the immune group and was very effective on motility of S. stercoralis larvae in vitro.

Royal jelly attenuates azathioprine induced toxicity in rats

In the present study, we investigated the potential protective effects of royal jelly against azathioprine-induced toxicity in rat. Intraperitoneal administration of azathioprine (50mg/kgB.W.) induced a significant decrease in RBCs count, Hb concentration, PCV%, WBCs count, differential count and platelet count, hepatic antioxidant enzymes (reduced glutathione and glutathione s-transferase) and increase of serum transaminases (alanine aminotransferase and aspartate aminotransferase enzymes) activities, alkaline phosphatase and malondialdehyde formation. Azathioprine induced hepatotoxicity was reflected by marked pathological changes in the liver. Oral administration of royal jelly (200mg/kgB.W.) was efficient in counteracting azathioprine toxicity whereas it altered the anemic condition, leucopenia and thrombocytopenia induced by azathioprine. Furthermore, royal jelly exerted significant protection against liver damage induced by azathioprine through reduction of the elevated activities of serum hepatic enzymes. Moreover, royal jelly blocked azathioprine-induced lipid peroxidation through decreasing the malondialdehyde formation. In conclusion, royal jelly possesses a capability to attenuate azathioprine-induced toxicity.

Liver transplantation for HBsAg-positive recipients using grafts from HBsAg-positive deceased donors

This study reports our experience using deceased donor liver grafts from HBsAg-positive donors. We performed eight cases of liver transplantation (LT) using grafts from deceased HBsAg-positive donors between November 2005 and October 2010. The median age of donors was 48 years (range: 26-64). HBV DNA in the serum of donors ranged from 44 to 395 IU/ml, but HBeAg in all donors was negative. Preoperative laboratory and liver biopsy samples revealed the absence of definitive cirrhotic features and hepatitis. All recipients showed HBsAg positive preoperatively except one patient with HBsAg(-) status post previous LT for HBV related liver cirrhosis. The median age was 60 years (range: 46-76) at LT. Post-LT antiviral management consisted of hepatitis B immunoglobulin and antiviral nucleos(t)ide analogues. The median follow-up period was 25.5 months (range: 14-82). Of eight recipients, two recipients experienced serum HBsAg and HBV DNA disappearance postoperatively. Three recipients died of HBV-unrelated causes. The remaining five recipients were stable with normal liver function and no marked pathologic changes on follow-up biopsies. This experience shows that LT using grafts from deceased HBsAg-positive donors is feasible, and may represent a valuable expansion of the pool of organ donors with appropriate antiviral management and monitoring.

Development of Some Larval Nematodes in Experimental and Natural Animal Hosts: An Insight into Development of Pathological Lesions vis‐a‐vis Host‐Parasite Interactions

Infective third-stage larvae of three spiruroid nematodes, Ascarops strongylina and Physocephalus sexalatus of pigs and Spirocerca lupi of dogs, were recovered from 14 species of coprophagous beetles belonging to 4 different genera. These larvae were fed to rabbits and/or guinea pigs to study their development in these experimental hosts. Larvae of A. strongylina reached the adult stage in all rabbits and one guinea pig. The adult worms recovered in these hosts were 40% and 4%, respectively, and became diminutive in comparison to their natural hosts. The larvae of P. sexalatus became reencysted in the gastric wall of rabbits inducing marked pathological changes. The infective larvae of S. lupi became reencapsulated in the stomach wall of the rabbit and also showed development in the aortic wall. Adults of Toxocara canis of dog, collected from 5 different regions of the Indian subcontinent, varied significantly in size. The mouse passage of infective larvae of one of these types led to the recovery of the adults from the experimental dogs that were smaller in size and caused severe pathology in natural experimental hosts. Developmental effects shown in experimental hosts and host specificity are of value in understanding the evolution of nematode parasitism.

Enhanced Liver Autophagic Activity Improves Survival of Septic Mice Lacking Surfactant Proteins A and D

Autophagy is a protective cellular mechanism in response to various stresses, including sepsis. Sepsis is defined as systemic inflammation by infection. Surfactant protein A and D (SP-A and SP-D) are involved in host defense, regulation of inflammation, and homeostasis, but their roles in the autophagic activity and relevant gene expression in sepsis are unclear. In this study, mice lacking SP-A and SP-D (SP-A/D KO mice) and background-matched wild-type (WT) C57BL/6 mice underwent either cecal ligation and puncture (CLP) or sham surgery. The results showed that SP-A/D KO mice had lower mortality than WT mice in CLP sepsis. Liver tissues showed marked pathological changes in both septic SP-A/D KO and WT mice 24 hrs after CLP treatment; and quantitative analysis of liver histopathology revealed significant difference between septic SP-A/D and septic WT mice. SP-A/D KO mice had higher basal and sepsis-induced level of autophagy than WT mice (p < 0.05), as judged by Western blot and electron microscopic analyses. The expression of 84 autophagy-related genes revealed differential basal and sepsis-induced gene expression between SP-A/D KO and WT mice. The expression increased in three genes and decreased in four genes in septic WT mice, as compared to septic SP-A/D KO mice (p < 0.05). Furthermore, differential responses to sepsis between SP-A/D KO and WT mice were found in six signaling pathways related to autophagy and apoptosis. Therefore, enhanced autophagic activity improves the survival of septic SP-A/D KO mice through the regulation of liver autophagy/apoptosis-related gene expression and signaling pathway activation.

Langendorff-Perfüze Sıçan Kalbinde İskemi Süresi ile İskemi/Reperfüzyon Hasarı Arasındaki İlişki: Değerlendirme Kriterleri Neler Olmalı?

Amaç: Langendorff izole perfüze kalp modelinde yapılan çalışmalarda, iskemi sürelerinin ve hasar değerlendirme kriterlerinin çeşitliliği, sonuçların yorumlanmasını zorlaştırmaktadır. Bu çalışmada, izole sıçan kalplerinde farklı iskemi süreleri ile iskemi sonrası miyokardiyal fonksiyonel iyileşme, doku canlılığı ve ultrastrüktürel değişiklikler arasındaki ilişkinin araştırılması ve sonuçların doğru yorumlanabilmesi için kullanılması gereken kriterlerin belirlenmesi amaçlanmıştır. Gereç ve Yöntemler: Sabit akımlı Langendorff düzeneğinde kalpler, sürekli perfüzyon (kontrol), 15 (İskemi15), 30 (İskemi30) veya 45 (İskemi45) dakika global iskemi sonrasında 30 dakika reperfüzyon uygulanan gruplara ayrılmıştır. İzole kalplerde LVDP, +dP/dtmaks, -dP/dtmaks, kalbin dakikadaki atım hızı, aritmi insidansı ve süresi ölçülmüştür. Koroner akım örneklerinden kreatin kinaz-MB (CK-MB) tayini, kalp dokusu kesitlerinde trifeniltetrazolyum boyama ve elektron mikroskobu ile morfolojik değerlendirmeler yapılmıştır (LVDP; LVDP = LV sistolik basınç – LV diyastolik basınç). Bulgular: Kontrol ve İskemi15 gruplarında fonksiyonel parametrelerin tümü deney süresince değişmemiştir. İskemi30 grubunda sol ventrikül basınç gelişimi, kasılmanın maksimum hızı ve gevşemenin maksimum hızı erken reperfüzyon döneminde azalmış, zamana bağlı maksimum kasılma değeri reperfüzyon sonunda bazal değere dönmüş, kalp hızı azalmıştır. İskemi45 grubunda bütün fonksiyonel parametreler erken reperfüzyon döneminde azalmış ve reperfüzyon sonunda bazal değerlere dönmüş, kalp hızı değişmemiştir. İskemi uygulanan bütün kalplerde aritmi skorları artmıştır. Kontrol, İskemi15 ve İskemi30 gruplarında CK-MB düzeyi artmamış, trifeniltetrazolyum boyama sonuçları bu gruplarda geri dönüşümsüz doku hasarı meydana gelmediğini göstermiştir. İskemi45 grubunda hem CK-MB düzeyi artmış hem de nekrotik alan varlığı gözlenmiştir. Morfolojik çalışmalarda miyofibril skorları yüksek olmamakla birlikte en belirgin ultrastrüktürel değişiklikler İskemi15 grubunda görülmüştür. İskemi süresi arttıkça ödem, glikojen, mitokondri ve nükleus skorları olarak ifade edilen ultrastrüktürel değişiklikler azalmıştır. Sonuç: Çalışmamızın sonuçları, Langendorff izole perfüze sıçan kalplerinde yapılan iskemi reperfüzyon çalışmalarında sonuçların doğru yorumlanabilmesi için fonksiyonel parametrelerin morfolojik ve biyokimyasal verilerle birlikte değerlendirilmesi gerektiğini göstermiştir.

Putative roles for a rhamnose binding lectin in Flavobacterium columnare pathogenesis in channel catfish Ictalurus punctatus

Columnaris disease, caused by the bacterial pathogen Flavobacterium columnare, continues to be a major problem worldwide and commonly leads to tremendous losses of both wild and cultured freshwater fish, particularly in intensively farmed aquaculture species such as channel catfish. Despite its ecologic and economic impacts, the fundamental molecular mechanisms of the host immune response to this pathogen remain unclear. While F. columnare can induce marked pathologic changes in numerous ectopic tissues, the adhesion of F. columnare to the gill in particular is strongly associated with pathogen virulence and host susceptibility. Recently, in this regard, using RNA-seq expression profiling we found that a rhamnose-binding lectin (RBL) was dramatically upregulated in the gill of fish infected with F. columnare (as compared to naïve fish). Thus, in the present study we sought to further characterize and understand the RBL response in channel catfish (Ictalurus punctatus). We first identified two distinct catfish families with differential susceptibilities to columnaris disease; one family was found to be completely resistant while the other was susceptible (0% mortality versus 18.3% respectively, P < 0.001). Exclusively, in the susceptible family, we observed an acute and robust upregulation in catfish RBL that persisted for at least 24 h (P < 0.05). To elucidate whether RBL play a more direct role in columnaris pathogenesis, we exposed channel catfish to different doses of the putative RBL ligands l-rhamnose and d-galactose, and found that these sugars, protected channel catfish against columnaris disease, likely through competition with F. columnare binding of host RBL. Finally, we examined the role of nutritional status on RBL regulation and found that RBL expression was upregulated (>120-fold; P < 0.05) in fish fasted for 7 d (as compared to fish fed to satiation daily), yet expression levels returned to those of satiated fish within 4 h after re-feeding. Collectively, these findings highlight putative roles for RBL in the context of columnaris disease and reveal new aspects linking RBL regulation to feed availability.

Clinicopathologic, Gross Necropsy, and Histologic Findings After Intramuscular Injection of Carprofen in a Pigeon (Columba livia) Model

To evaluate the pathologic effects of carprofen in a pigeon model (Columba livia), 52 young adult pigeons were used in a randomized control study design. Sixteen pigeons were randomly assigned to 1 of 3 treatment groups and received carprofen by intramuscular injection at dosages of either 2, 5, or 10 mg/kg once daily for 7 days. Four pigeons served as saline-injected controls. Four pigeons from each group and 1 control pigeon were randomly selected on days 2, 4, 6, and 8 to obtain blood samples and then were euthanatized and submitted for necropsy. Histologic lesions in pectoral muscle, liver, kidney, and digestive tract tissue samples were ranked in severity as 0, normal/not present; 1, minimal; 2, mild; 3, mild to moderate; 4, moderate; 5, moderate to marked; and 6, marked pathologic changes. Two-way analysis of variance (day x dose) and pairwise t tests revealed significant (P < or = .05) mild decreases in total protein and glucose concentrations and marked increases in aspartate aminotransferase and alanine aminotransferase enzyme activities after carprofen treatments. Gross lesions in carprofen-treated pigeons were pale injection sites (23/48 [47.9%]), mottled yellow livers (9/48 [18.8%]), and congestion of small intestines (7/48 [14.6%]). Liver, kidney, and muscle injection sites had significantly increased (P < or = .05) severity of histologic lesions. In pigeons, intramuscular administration of carprofen is associated with increased aspartate aminotransferase and alanine aminotransferase enzyme concentrations, gross lesions in muscle injection sites and liver, and histologic lesions in liver and muscle.

Fatal Intoxication Because of Trihexyphenidyl

Trihexyphenidyl (THP) is an anticholinergic agent with forensic toxicological interest. We present a case of a 59-year-old woman with a history of paranoid disorder, who was found dead in the house where she lived alone. The autopsy findings revealed no marked pathological changes. Toxicological analysis based on gas chromatography-mass spectrometry (GC-MS) analysis revealed THP and its major metabolite (hydroxy-THP) in blood and urine, with THP concentrations of 0.053 and 0.560 mg/L, respectively. The blood and urine ethanol concentrations were low 0.096 and 0.100 g/L, respectively. Based on these results, we determined the cause of death to be THP poisoning. It is suggested that rare case of death associated with THP overdosage should be taken in conjunction with central nervous system depressants (benzodiazepines, ethanol) and/or with other pathological disorders. Thus, our case could not be supportive for this allegation.

Biochemical and histopathological effects of administration various levels of Pomposia (Syzygium cumini) fruit juice as natural antioxidant on rat health.

The aim of the current investigation was to evaluate the effects of administration various levels (400, 800 and 1,200ppm) of pomposia extracts as natural antioxidant in comparison with BHT as synthetic antioxidant on some biochemical activities and histopathological examination of rats. Some of biochemical tests i.e. Alkaline phosphatase, transaminases]Aspartate transferase (AST) and alanine transferase (ALT) [,bilirubin, urea and uric acid were conducted. Histopathological examinations were carried out on the liver and kidney tissue of rats administrated tested substances. The biochemical results indicated that the administration of polyphenolic compounds present in pomposia juice did not cause any significant (p ≥ 0.05) changes in the biochemical parameters whereas the administration of BHT at 200ppm caused significant (p ≤ 0.05) increase in the activities of enzymes relevant to the functions of liver and kidney. Microscopically examinations of liver and kidney of rat administered various levels of pomposia juice had the same character as that of control rats (this means that the polyphenolic compounds present in pomposia juice did not cause any adverse affect in liver and kidney), in contrast the administration of 200ppm of BHT caused marked pathological changes in liver and kidney of rats. The results of the current investigation suggest using pomposia juice as safe food grade substance.

Cyclosporine A-induced acute hepatotoxicity in guinea pigs is associated with endothelin-mediated decrease in local hepatic blood flow

Aims To bring further insight into the mechanism of cyclosporine A (CsA)-induced hepatotoxicity, the acute effect of CsA on local hepatic blood flow (LHBF) and its association with systemic hemodynamics, histopathological and biochemical indicators of liver toxicity were studied in guinea pigs in vivo. The association of endothelin (ET) and/or Cremophor-EL (C-EL, vehicle in parenteral CsA preparation) with CsA effects was also investigated. Main methods Animals were assigned into five groups; control, CsA, C-EL, Bosentan (non-selective ET receptor antagonist) + CsA, and BQ-123 (ET A receptor antagonist) + CsA. CsA was infused intravenously (i.v.) at 20 and 10 mg/kg doses by 15 min interval. Antagonists were administered 15 min before CsA infusion. LHBF and mean arterial blood pressure (MAP) changes were simultaneously recorded. Blood and liver samples were collected for biochemical and histopathological examinations. Key findings CsA, but not C-EL, decreased LHBF by 53.3% at the end of 30 min. Although being non-significant, CsA slightly increased MAP suggesting that, CsA-induced acute decrease in LHBF was likely independent of MAP changes. Bosentan (5 mg/kg, i.v.) and BQ-123 (1 mg/kg, i.v.) pre-treatments prevented the CsA-induced decrease in LHBF suggesting that CsA decreases LHBF through an ET-related mechanism. Additionally, CsA, but not its vehicle C-EL, caused marked acute pathological changes in the liver morphology. Significance CsA-induced findings of acute hepatotoxicity were prevented by bosentan and BQ-123 pre-treatments. Thus, CsA seems to exert acute hepatotoxic effect through ET-related mechanisms.

Pathological changes in the lung and brain of mice during heat stress and cooling treatment.

Heatstroke often leads to multiple organ dysfunction syndrome (MODS) with a death rate of 40% or a neurological morbidity of 30%. These high rates in patients with heatstroke are largely due to the progression of heat stress to MODS, resulting in no specific treatment available. This study aimed to develop a mouse model of heat stress and determine the pathological changes in the lung and brain during heat stress and cooling treatment. A mouse model of heat stress was established in a pre-warmed incubator set at 35.5 ± 0.5°C and with a relative humidity of 60% ± 5%. Rectal temperature was monitored, and at a temperature of 39 °C, 40 °C, 41 °C, or 42 °C, the mice were sacrificed. The remaining animals were removed from the incubator and cooled at an ambient temperature of 25 ± 0.5 °C and a humidity of 35% ± 5% for 12 or 24 hours at a temperature of 41 °C or for 6 hours at a temperature of 42 °C. The control mice were sham-heated at a temperature of 25 ± 0.5 °C and a humidity of 35% ± 5%. The lungs and brains of all animals were isolated. Hematoxylin and eosin staining and light microscopy were performed to detect pathological changes. All mice demonstrated a uniform response to heat stress. A low degree of heat stress induced marked pathological changes of the lungs. With the rise of the temperature to 42°C, progressively greater damage to the lungs with further congestion of the lung matrix, asystematic hemorrhage of alveolar space, abscission of alveolar epithelial cells, and disappearance of pulmonary alveolus tissue structure were detected. However, absorption of congestion and hemorrhage as well as recovery of pulmonary alveolus tissue structure was observed following cooling treatment at an ambient temperature. With a low degree of heat stress, the brain only showed moderate edema. Neuronal denaturation and necrosis were detected at a temperature of 42°C. Interestingly, the lesions in the brain were further aggravated at 42 °C regardless of cooling treatment, but recovery was observed after cooling treatment at 41 °C. The pathological changes of the lungs and brain of mice showed distinctive lesions following heat stress and cooling treatment, and they were correlated with the time and duration of cooling treatment. The results of this study are helpful for further study of the mechanisms linking heatstroke.

Marked pathological changes proximal and distal to the site of rupture in acute Achilles tendon ruptures

A laboratory study was performed to evaluate the histopathological features of the macroscopically intact portion of the Achilles tendon in patients undergoing surgery for an acute rupture of the Achilles tendon. Tendon samples were harvested from 29 individuals (21 men, 8 women; mean age: 46±12) who underwent repair of an Achilles tendon tear tear, and from 11 male patients who died of cardiovascular events (mean age: 61). Three pieces of tendon were harvested: at the rupture site, 4cm proximal to the site of rupture, 1cm proximal to the insertion of the Achilles tendon on the calcaneum. Slides were assessed using a semiquantitative grading scale assessing fiber structure and arrangement, rounding of the nuclei, regional variations in cellularity, increased vascularity, decreased collagen stainability, and hyalinization. Intra-observer reliability of the subscore readings was calculated. The pathological features were significantly more pronounced in the samples taken from the site of rupture than in the samples taken proximally and distal to it (0.008<P<0.01). There were no significant differences in the mean pathologic sum-scores in the samples taken proximally and distal to the site of rupture. Unruptured Achilles tendons, even at an advanced age, and ruptured Achilles tendons are clearly part of two distinct populations, with the latter demonstrating histopathological evidence of failed healing response even in areas macroscopically normal.

Interferon Regulatory Factor 3 Attenuates Reovirus Myocarditis and Contributes to Viral Clearance

Apoptosis is a pathological hallmark of encephalitis and myocarditis caused by reovirus in newborn mice. In cell culture models, the antiviral transcription factor interferon regulatory factor 3 (IRF-3) enhances reovirus-induced apoptosis following activation via retinoic acid inducible gene I and interferon promoter-stimulating factor 1. To determine the role of IRF-3 in reovirus disease, we infected newborn IRF-3(+/+) and IRF-3(-/-) mice perorally with mildly virulent strain type 1 Lang (T1L) and fully virulent strain type 3 SA+ (T3SA+) and monitored infected animals for survival. Both wild-type and IRF-3(-/-) mice succumbed with equivalent frequencies to infection with T3SA+. However, the absence of IRF-3 was associated with significantly decreased survival rates following infection with T1L. The two virus strains achieved similar peak titers in IRF-3(+/+) and IRF-3(-/-) mice in the intestine, brain, heart, liver, and spleen. However, by day 12 postinoculation, titers in all organs examined were 10- to 100-fold higher in IRF-3(-/-) mice than those in wild-type mice. Increased titers were associated with marked pathological changes in all organs examined, especially in the heart, where absence of IRF-3 resulted in severe myocarditis. Cellular and humoral immune responses were equivalent in wild-type and IRF-3(-/-) animals, suggesting that IRF-3 functions independently of the adaptive immune response to enhance reovirus clearance. Thus, IRF-3 serves to facilitate virus clearance and prevent tissue injury in response to reovirus infection.

The ultrastructural effects and immunolocalisation of fumonisin B&lt;sub&gt;1&lt;/sub&gt; on cultured oesophageal cancer cells (SNO)

Numerous investigations have shown that fumonisin B1 (FB1 )i s the causal agent in a range of animal toxicities, including leucoencephalomalacia, pulmonary oedema and renal and hepatic cancer in rats and mice. Fumonisin B1 has also been implicated in the aetiology of oesophageal cancer in South Africa. Human data are lacking, however, and the International Agency for Research on Cancer has accordingly classified this mycotoxin as a Type 2B carcinogen. This study investigated the ultrastructural effects of FB1 cytotoxicity on a human oesophageal carcinoma cell line (SNO). The pathological changes induced by FB1 were determined using transmission and scanning electron microscopy. Immunocytochemistry was used to immunolocalise FB1 (monoclonal anti-FB1) within the cells. The results showed marked pathological changes that included enlargement or microsegregation of the nucleus, microsegregation of the nucleolus, and swelling and elongation of mitochondria, as well as signs of membrane damage. These cytotoxic effects were associated with the action of FB1, since the toxin was internalised in nuclei, mitochondria and the cytoplasm of affected cells. This study shows that FB1 may exert its biological effects in SNO cells through binding to cellular macromolecules or membrane components within the affected organelles. : oesophageal cancer, fumonisin B1, cell culture, immunocytochemistry

Abnormalities of masseter inhibitory reflex in patients with episodic tension-type headache

To investigate the masseter inhibitory reflex (MIR) and its eventual changes in patients with episodic tension-type headache (TTH). MIR was studied in 21 patients with episodic TTH and 30 healthy subjects, with age and sex matched to the study cohort. Median age of patients was 17.0 years (ranged 16~49 years), median duration of disease 12 months (1~5 years), and median frequency of headache 7.5 d per month. The second period of suppression (S2) of MIR was reduced in intensity and duration in 10% of controls and 66.7% (confidence interval (CI)=45.3%~85%; P<0.05) of patients with episodic TTH (chi(2)=74.9; P<0.001). In 3 (14.3%) of patients with episodic TTH, S2 was completely absent. No significant correlation between the duration of disease and headache frequency was found. Our results confirm the link between episodic TTH and reduction or absence of S2. Teenage patients with episodic TTH may exhibit marked pathological changes in S2 in contrast to older individuals.

겨울철 양식장 환경에서 Tai koi, Anabas testudineus (BLOCH)의 임상병리학적 특징

방글라데시의 양식어류 생산에서 가장 큰 문제점은 어병이며, 어병을 진단하는 위해서는 병변부의 조직병리학적 진단이 필수적이다. 방글라데시의 주요 잉어과에 속하는 몇몇 어류에 대해서는 조직병리학적 연구가 진행되었지만, 고유종(indigenous species)이면서 담수 소형어류인 어종에 대해서는 거의 연구가 이루어지지 않은 상태이다. 그러므로 본 연구는 보양식으로 경제적 가치가 높은 Thai koi (Anabas testudineus)에 대한 조직병리학적 특성을 규명하고자 하였다. 2006년 8월부터 2007년 2월까지 7개월간 방글라데시 미멘싱(Mymensingh)지역의 두 양어장에서 임상학적 그리고 조직병리학적 관찰을 통해 Thai koi(A. testudineus)의 건강상태를 조사하였다. 어류개체의 홍반, 출혈, 외상, 원생동물 피낭(cyst)과 같은 비정상적 증상에 대한 임상학적 진단을 월별로 조사하였다. 동절기양어장의 수질 요인 중에서 수온, 용존산소량과 같은 변수는 어류에게 적합하지 않은 것으로 나타났다. 임상학적으로는 12월부터 1월 사이에 병에 걸린 어류가 더 많았고, 8월과 9월 사이 그리고 2월에는 외형상으로는 거의 정상에 가까웠다. 12월과 1월에 피부탈락, 피부외상, 궤양과 꼬리지느러미의 손실과 같은 여러 가지의 임상학적 증상이 나타났다. 조직병리학적 측면에서 8월과 9월 기관의 구조는 정상으로 나타났다. 10월과 11월 사이에는 미미한 병적 증상들이 발견되었고, 12월과 1월에는 조직 괴사, 핵응축(pyknosis), 염증, 출혈, 이상비대(hypertrophy), 세포과형성(hyperplasia), 1 2차 새판(gill lamellae)의 손상과 같은 현저한 조직병리학적 변화가 발견되었다. 반면에 2월에는 어류의 병적증상이 점차적으로 감소하였다. 개개의 어류양식장을 고찰해 보았을 때, Relance Aqua Farm의 어류가 Sotota Mastshya Hatchery의 어류보다 더 감염률이 높았다. 본 연구 결과는, Thai koi의 월별 임상학적 조직병리학적 진단을 통해, 어병 발생 시기를 예측하고, 예방하기 위한 기초자료로 활용될 수 있다. Investigation on health conditions of Thai koi (Anabas testudineus) were carried out through clinical and histopathological observations from different farms of Mymensingh district for seven months during August 2006 to February 2007. Fish sampling and water quality parameters (temperature, dissolved oxygen and pH) were monitored on a monthly basis. Clinical examination of fishes was also carried out for any kind of abnormalities at monthly intervals. Samples of skin, muscle, gill, liver and kidney were observed by histological technique. Among the water quality parameters the values of water temperature, dissolved oxygen were found to be at unfavorable level for fish during the colder months in the farms. Clinically it was observed that fishes were more affected from December to January and almost normal in appearance during August to September and February. Different clinical symptoms like scale loss, dermal lesion, ulcer and loss of caudal fin were noticed in December and January. In histopathological study, structures of fish organs were normal from August to September. In the months of October and November, minor pathologies were found to be started. Marked pathological changes like necrosis, pyknosis, inflammation, hemorrhage, hypertrophy, hyperplasia, missing of primary and secondary gill lamellae were observed in the months of December and January. Whereas, in the month of February the pathological condition of fish gradually reduced. Again when considered individual fish farm, fishes of Reliance Aqua Farm were more affected than Sotota Matshya Hatchery. The study showed that severity of clinical and pathological changes were increased in December and January. During the period EUS and protozoan diseases were noticed in A. testudineus of the investigated farms.

The effect of 2,3-dihydroxybenzoic acid and tempol in prevention of vancomycin-induced nephrotoxicity in rats

One of the major adverse effects of vancomycin (VAN) is nephrotoxicity, which the mechanism is not fully understood. However, there is some evidence that oxidative injury could be involved in its pathogenesis. In this study, we examined two antioxidants 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) a superoxide dismutase mimetic and 2,3-dihydroxybenzoic acid (DHB) an iron chelator in VAN-induced nephrotoxicity in rats. DHB at doses of 50 and 100 mg/kg and tempol at doses of 7.5, 15 and 30 mg/kg were administered subcutaneously to rats 30 min prior to intraperitoneal injection of 200 mg/kg VAN. Drug administrations were done every 12 h for 7 days. In animals which received only VAN, the activity of urinary γ-glutamyl-transferase (GGT) decreased and the activity of lactate dehydrogenase (LDH) in urine increased significantly compared to controls. Serum urea and creatinine (Cr) concentrations and the weight of animals’ kidneys increased and body weights were decreased significantly in this group compared to controls. DHB at both doses normalized the GGT activity, but only at the higher dose restore the LDH activity. Both doses of DHB ameliorated the rise in serum urea and Cr concentrations and improved the changes in kidney and body weights significantly. Tempol did not show any beneficial effects at all. There were marked pathologic changes in tubules of kidneys of VAN treated animals. The tissue injury was prevented by both doses of DHB and there was almost no sign of tubular injury in 100 mg/kg treated group. Tempol in any doses could not prevent the tissue injury and there were significant differences in tissue injury in all tempol treated rats with controls. It seems that VAN-induced nephrotoxicity is at least partly due to free radical formation. Hydroxyl radicals might play a major role in VAN-induced nephrotoxicity, since an iron chelator (DHB) could reverse the adverse effects. However, production of other radicals such as superoxide is also probable.

Protective Effect of Serum Thymic Factor, FTS, on Cephaloridine-Induced Nephrotoxicity in Rats

Serum thymic factor (FTS), a thymic peptide hormone, has been reported to increase superoxide disumutase (SOD) levels in senescence-accelerated mice. In the present study, we examined the effect of FTS on cephaloridine (CER)-induced nephrotoxicity in vivo and in vitro. We previously reported that CER led to extracellular signal-regulated protein kinase (ERK) activation in the rat kidney. So, we also investigated whether FTS has an effect on ERK activation induced by CER. Treatment of male Sprague-Dawley rats with intravenous CER (1.2 g/kg) for 24 h markedly increased BUN and plasma creatinine levels and urinary excretion of glucose and protein, decreased creatinine clearance and also led to marked pathological changes in the proximal tubules, as revealed by electron micrographs. An increase in phosphorylated ERK (pERK) was detected in the nuclear fraction prepared from the rat kidney cortex 24 h after CER injection. Pretreatment of rats with FTS (50 microg/kg, i.v.) attenuated the CER-induced renal dysfunction and pathological damage. FTS also suppressed CER-induced ERK activation in the kidney. In vitro treatment of the established cell line, LLC-PK1 cells, with FTS significantly ameliorated CER-induced cell injury, as measured by lactate dehydrogenase (LDH) leakage. Our results, taken together with our previous report that MEK inhibitors ameliorated CER-induced renal cell injury and ERK activation induced by CER, suggest that FTS participates in protection from CER-induced nephrotoxicity by suppressing ERK activation induced by CER.