A case of complete transection of right main bronchus in a child: Role of thoracoscopy and bronchoscopy.

Isolated tracheobronchial injuries are extremely rare in children and challenging due to life threatening complications. Blunt trauma to chest, especially in pediatric age group, is usually associated with multi-organ involvement and high mortality rate. These patients rarely reach a hospital. We have described here a case of complete transection of right main bronchus in a child, without hilar vascular injury, and its successful management, emphasizing the role of bronchoscopy and thoracoscopy.

Tumour immunomodulation: mucins in resistance to initiation and maturation of immune response against tumours.

Mucins are high molecular weight glycoproteins designed for cellular protection and sensing the external environment. Aberrant glycosylation and altered mucin expression seen in cancers are implicated in mucin-dependent refraction to immunosurveilance and immunosuppressive induction around the tumour. Although mucins provide molecular targets for immune system's tumour recognition, their characteristics dictate that the nature of immune response required for recognition and lyses of mucin-expressing tumours needs to follow predominantly a MHC-unrestricted αß TCR-mediated effector cell response. Frequent loss of dendritic cells maturation and elimination of reactive lymphocytes altered adhesive and anti-adhesive properties of the mucins, promote tumour survival and escape from the immune response.

Autoimmune hemolytic anaemia in Hodgkin's lymphoma.

Autoimmune hemolytic anaemia is a rare presentation of Hodgkin's lymphoma though its association with Non- Hodgkin's lymphoma is well known. It is usually detected at the time of diagnosis when it accompanies Hodgkin's and rarely precedes it. It is a warm immune hemolytic anemia which is responsive to steroids and rituximab. We hereby report a case of advanced Hodgkin's disease who presented as AIHA.

Expression of Wnt 3a, ß-catenin, cyclin D1 and PCNA in mouse dentate gyrus subgranular zone (SGZ): a possible role of Wnt pathway in SGZ neural stem cell proliferation.

In mammalian dentate gyrus subgranular zone, the addition of new neurons throughout adulthood is a remarkable form of structural plasticity. Yet, the molecular controls over subgranular zone neural stem cell proliferation, survival, and differentiation are poorly understood. In this study we analysed the expression of Wnt 3a, ß-catenin, cyclin D1 and proliferating cell nuclear antigen in mouse subgranular zone to elucidate the involvement of Wnt pathway in subgranular zone neural stem cell proliferation. We performed immunohistochemistry and RT-PCR for the above molecules on adult and postnatal developing hippocampal tissues of mice, respectively. RT-PCR analysis showed a gradual increase in expression of mRNA of Wnt 3a, ß-catenin, cyclin D1 and proliferating cell nuclear antigen as the postnatal hippocampus developed, and immunohistochemical analysis showed a highly positive immunoreactive expression for Wnt 3a, ß-catenin, cyclin D1 and proliferating cell nuclear antigen in the subgranular zone cells. Together, our data suggested that the Wnt pathway is activated in subgranular zone and could play an important role in regulating subgranular zone neural stem cell proliferation in mouse hippocampus.

Vulval tuberculosis - an unusual presentation of disseminated tuberculosis.

Extrapulmonary involvement can occur in isolation or along with a pulmonary focus as in the case of patients with disseminated tuberculosis. Vulval TB is very rare and the presentation can be quite variable, and may be misdiagnosed as sexually transmitted disease. We herein report a young lady with disseminated TB presenting as Vulval TB.

A fibre cocktail of fenugreek, guar gum and wheat bran reduces oxidative modification of LDL induced by an atherogenic diet in rats.

BACKGROUND: LDL (low-density lipoprotein) oxidation is a key trigger factor for the development of atherosclerosis. Relatively few studies exist on the impact of dietary fibre on LDL oxidation. This study was undertaken to evaluate the influence of a novel fibre mix of fenugreek seed powder, guar gum and wheat bran (Fibernat) on LDL oxidation induced by an atherogenic diet. METHOD: Male Wistar albino rats were administered one of the following diets: (1) a control diet that was fibre-free (Group I); (2) an atherogenic diet containing 1.5% cholesterol and 0.1% cholic acid (Group II) or (3) an atherogenic diet supplemented with Fibernat (Group III). Peroxidative changes in low-density lipoprotein (LDL) and the oxidative susceptibility of LDL and the LDL + VLDL (very low-density lipoprotein) fraction were determined. As a corollary to the oxidative modification theory, the titer of autoantibodies to oxidised LDL (oxLDL) was determined at various time points of the study. In addition, plasma homocysteine (tHcy) and lipoprotein (Lp (a)), apolipoprotein (apoB), cholesterol, triglyceride, phospholipid and alpha-tocopherol content of LDL were determined. RESULTS: A decrease in malonaldehyde (MDA) content (p<0.05) and relative electrophoretic mobility (REM) of LDL was observed in the group III rats as compared to the group II rats. An increase in lag time to oxidation (p<0.01) and decrease in maximum oxidation (p<0.01) and oxidation rate (p<0.01) were observed in the LDL + VLDL fraction of group III rats. In group II rats, formation of autoantibodies to oxLDL occurred at an earlier time point and at levels greater than in the group III rats. Fibernat, had a sparing effect on LDL alpha-tocopherol, which was about 51% higher in the group III rats than in the group II rats; apo B content of LDL was reduced by 37.6% in group III rats. LDL of group III rats displayed a decrease in free and ester cholesterol (p<0.01) as compared to that of group II. A decrease in plasma homocysteine (p<0.01) and an increase in GSH (p<0.05) were also observed in group III rats when compared with that of group II. CONCLUSION: Fibernat administration appears to combat oxidative stress resulting in a trend to lower oxidative modification of LDL. In addition, the cholesterol and apo B content of LDL were reduced significantly with a sparing effect on LDL alpha-tocopherol. This novel fibre preparation could be an effective diet therapy and therefore needs further investigation.

Effect of the food flavour cinnamaldehyde on the antioxidant status of rat kidney.

Cinnamaldehyde, a food flavour, has a high potential for human consumption in India. In this study, we evaluated the effect of cinnamaldehyde on the antioxidant status of the rat kidney. Rats were given cinnamaldehyde orally by gavage at dose levels of 2.14, 6.96, 22.62 and 73.5 mg/kg body weight/day for the period of 10, 30 and 90 days. The non-enzymatic antioxidants ascorbic acid, alpha-tocopherol and reduced glutathione were decreased while the antioxidant enzymes, superoxide dismutase, glutathione peroxidase and glutathione-s-transferase were increased. Catalase was decreased and thiobarbituric acid-reactive substances were increased only in the kidney of rats treated with cinnamaldehyde at the dose level of 73.5 mg/kg body weight/day during an exposure period of 90 days and not in the kidney of other cinnamaldehyde-treated rat groups. Thus, cinnamaldehyde has an effect on the antioxidant status of rat kidney and its effect is time- and dose-dependent.

In vivo micronucleus assay and GST activity in assessing genotoxicity of plumbagin in Swiss albino mice.

Information available on the mutagenicity of a large number of indigenous drugs commonly employed in the Siddha and Ayurveda systems of medicine is scanty. In this context, the current investigation on plumbagin, 5-hydroxy-2methyl-1,4-napthoquinone, an active principle in the roots of Plumbago zeylanica used in Siddha and Ayurveda for various ailments, was carried out; 16 mg/kg b.w. (LD(50)) was fixed as the maximum dose. Subsequent dose levels were fixed as 50% and 25% of LD(50) amounting to 8 mg and 4 mg/kg b.w., respectively, and given orally for 5 consecutive days in 1% Carboxyl Methyl Cellulose (CMC) to Swiss albino mice weighing 25-30 g. The micronucleus assay was done in mouse bone marrow. Plumbagin was found to induce micronuclei at all the doses studied (4 mg/kg, 8 mg/kg, 16 mg/kg b.w.), and it proves to be toxic to bone marrow cells of Swiss albino mice. Animal treated with cyclophosphamide (40 mg/kg b.w.) served as positive control. In addition, glutathione S-transferase (GST) activity was observed in control, plumbagin (4 mg, 8 mg, 16 mg/kg b.w., respectively), and genotoxin-treated experimental group of animals. No significant change in GST activity was observed with plumbagin dose of 4 mg/kg b.w., whereas GST activity was significantly inhibited by higher doses of plumbagin (8 mg and 16 mg/kg b.w.) and cyclophosphamide.

Expression of the Gas7 gene and Oct4 in embryonic stem cells of mice.

Oct4 is a stem cell expression marker, and persistence of its expression retains pluripotency in embryonic stem (ES) cells. Our results indicate a pattern of gradual decrease in Oct4 expression, which is prominent in the blastocyst and markedly reduced in the gastrula and neurula. The presence of POU transcription factor-like domain in Gas7 prompted us to look for its expression in the early embryonic cells. We have observed high expression of the Gas7 protein in blastocysts that gradually decreased in the neurula stages. The localization of Gas7 was initially seen throughout the blastocyst, but was later confined to dorsal ectodermal regions of the neurula, conforming with its role in neuronal differentiation. Our data reveal that Gas7 might play a role in cellular migration and cell protection in the ES cells of mouse embryo.

Increased binding of LDL and VLDL to apo B,E receptors of hepatic plasma membrane of rats treated with Fibernat.

BACKGROUND: Research has focussed on the hypocholesterolemic effects of certain types of dietary fiber such as enhancing conversion of hepatic cholesterol to bile acids or increase in catabolism of low density lipoprotein (LDL) via the apo B,E receptor. AIM OF THE STUDY: The effect of oral administration of a unique fibre cocktail of fenugreek seed powder, guar gum and wheat bran (Fibernat) and its varied effects on some aspects of lipid metabolism and cholesterol homeostasis in rats were examined. METHODS: Rats were administered Fibernat along with the atherogenic diet containing 1.5 % cholesterol and 0.1 % cholic acid. Amounts of hepatic lipids, hepatic and fecal bile acids and activity of hepatic triglyceride lipase (HTGL) were determined. Transmission electron microscopic examination of the liver tissue and extent of uptake of (125)I-LDL and (125)I-VLDL by the hepatic apo B,E receptor was carried out. RESULTS: Food intake and body weight gain were similar between the 3 different dietary groups. Fibernat intake significantly increased apo B,E receptor expression in rat liver as reflected by an increase in the maximum binding capacity (B(max)) of the apo B,E receptor to (125)I-LDL and (125)I-VLDL. The activity of HTGL was increased by approximately 1.5-fold in Fibernat-fed rats as compared to those fed the atherogenic diet alone. A marked hypocholesterolemic effect was observed. Cholesterol homeostasis was achieved in Fibernat-fed rats. CONCLUSION: Two possible mechanisms are postulated to be responsible for the observed hypocholesterolemic effect a) an increase in conversion of cholesterol to bile acids and b) possibly by intra-luminal binding which resulted in increased fecal excretion of bile acids and neutral sterols. The resulting reduction in cholesterol content of liver cells coupled with upregulation of hepatic apo B,E receptors and increased clearance of circulating atherogenic lipoproteins-LDL and very low density lipoprotein (LDL and VLDL)-is the main mechanism involved in the hypocholesterolemic effect of Fibernat. The results suggest that Fibernat's effect on plasma LDL concentration is also possibly mediated by increased receptor-mediated catabolism of VLDL. Thus, Fibernat therapy is an effective adjunct to diet therapy and might find potential use in the therapy of hyperlipidemic subjects.

Amiodarone-induced phospholipidosis: an in vivo [14C]-acetate uptake study in rat.

Amiodarone (AD), a potent antiarrhythmic drug, is often associated with several adverse effects. It is shown to accumulate phospholipids in various tissues, and the impaired catabolism of phospholipids has been implicated in AD-induced phospholipidosis. The synthesis of phospholipids in tissues has not been dealt with. Hence, the incorporation of [14C]-acetate into phospholipids has been studied to understand the AD-induced phospholipidosis in lung and liver. A significant increase in lung and liver phospholipids was observed after 21 and 28 days of AD (175 mg/kg body weight/day) treatment. In the lung and liver, the incorporation of [14C]-acetate into all phospholipid fractions was elevated, while in the lung mitochondria phosphatidylcholine, phosphatidyl ethanolamine and the cardiolipin levels were significantly increased. The results indicate that, in addition to the impaired catabolism of phospholipid, AD treatment resulted in increased phospholipid synthesis.

Lipid peroxidation as a possible secondary mechanism of sterigmatocystin toxicity.

Sterigmatocystin (Stg), a major secondary metabolite of Aspergillus versicolor and A. nidulans, is the precursor of aflatoxin B1. In this study, male albino rats were treated with Stg-contaminated diet for 30 days, resulting in reduced levels of glutathione, ascorbic acid, and alpha-tocopherol. The activity of catalase in liver was reduced, whereas an increase in the activities of superoxide dismutase and glutathione peroxidase was observed. The levels of cytochrome P450, cytochrome b5, cytochrome b5 reductase, cytochrome c reductase, hydroxyl radical, and hydrogen peroxide formation significantly increased in the Stg- treated rat liver microsomes. Hepatic parenchymal cell injury, necrosis, and Kupffer cells proliferation were noticed in histological sections of liver from animals treated with Stg. Overall results suggest that generation of free radicals imposes depletion of antioxidants. This led to enhanced lipid peroxidation. The observed elevation of hepatic thiobarbituric acid reactive substances appears to originate mainly from the damaged Kupffer cells. As a result, elevated levels of serum marker enzymes were also observed.

Assessment of the no-observed-adverse-effect level (NOAEL) of gallic acid in mice.

Gallic acid is a naturally occurring plant phenol obtained by the hydrolysis of tannins and is known to show some pharmacological activities. The purpose of this paper is to establish the safety of gallic acid in mice. In this study, acute administration of gallic acid even at a dose as high as 5 g/kg body weight did not produce any signs of toxicity or mortality. In the subacute study, gallic acid at a dose of 1000 mg/kg body weight did not significantly alter the hematological parameters. Further, no appreciable change was noted in the various biochemical parameters such as SGOT and SGPT, as well as many serum constituents such as protein, cholesterol, urea and bilirubin. Therefore, from this study, it may be concluded that gallic acid is non-toxic up to a level of 5000 mg/kg body weight, when given orally. In addition, the subacute study indicated the absence of cumulative toxicity, as reflected by the non-significant alterations in the parameters investigated. The NOAEL was 5000 mg/kg body weight, the highest dose tested.

Adherence of Shigella dysenteriae 1 to human colonic mucin.

The pathogenic potential of Shigella is correlated with the ability of the organism to invade and multiply within the cells of colonic epithelium. Although invasion is the ultimate event, a preceding step is adherence. Shigella dysenteriae 1 preferentially adhered to colonic mucin and not to small intestinal mucin. The pathogen showed a very strong adherence pattern to human colonic mucin when compared with guinea pig and rat mucin. The adherence pattern of S. dysenteriae 1 was not altered on preincubation with monosaccharides present in mucins, suggesting that the receptor for the pathogen is not a simple sugar. Binding of S. dysenteriae 1 to human colonic mucin was not by weak hydrophobic forces. The bacterium also adhered to glycolipids, emphasizing the role of glycoconjugates as receptors for S. dysenteriae 1.

Serum alpha-N-acetylgalactosaminidase is associated with diagnosis/prognosis of patients with squamous cell carcinoma of the uterine cervix.

Serum alpha-N-acetylgalactosaminidase (NaGalase) is responsible for the deglycosylation of vitamin D(3)-binding protein (Gc protein). The deglycosylated Gc protein cannot be converted into major macrophage-activating factor (MAF), leading to immunosuppression. NaGalase is universally detected in a variety of cancer patients, but not in healthy individuals (Cancer Res. 56 (1997) 2827-2831). However, the diagnostic/prognostic utility of NaGalase in squamous cell carcinoma (SCC) of the uterine cervix is not known. To address this issue, the serum NaGalase was quantitatively determined in 210 patients with different stages of SCC of the uterine cervix. NaGalase levels were increased with the progression of the cancer. After radiotherapy, the increased levels returned toward or to normal levels in early stages (FIGO stage I-IIB) but not in advanced stages (FIGO stage III-IV). The present study revealed that the amount of NaGalase in the patient's bloodstream reflects the tumor burden and aggressiveness of the disease. We conclude that NaGalase is an independent predictor of diagnosis/prognosis in SCC of the uterine cervix, and therefore suggest that quantitative NaGalase alteration may reflect important differences in the immunological functions of these neoplasms.

Effect of amiodarone on the membrane bound enzymes of rat intestine.

Amiodarone, a cationic amphiphile known for its clinical efficacy as an antiarrhythmic agent, unfortunately causes serious side effects. The present study was undertaken to investigate its intestinal toxicity, on oral administration, using a Wistar rat model. The relationship of drug dose and duration on intestinal toxicity was investigated. Optimum changes were observed after 21 days of AD administration at a dose of 175 mg/Kg body wt/day and this dosage was used for further studies. Histological studies revealed decreased villi and crypt size and reduction in the cellularity of lamina propria. Marked reduction in the activities of Ca(2+)-ATPase, alkaline phosphatase, disaccharidases and Na+, K(+)-ATPase was observed. The reduction in the uptake of 14C-glucose and 14C-glycine, in vivo, was correlated to the reduction in the activities of these enzymes. The reduction in the activities of the intestinal membrane bound enzymes may be attributed to altered morphology of the villi and crypts.

Enzyme-linked PNA lectin-binding assay of serum T-antigen in patients with SCC of the uterine cervix.

The expression of Thomsen-Friendenreich antigen (T-Ag) is associated with enhanced metastatic potential, poor prognosis and decreased survival rate in a variety of malignancies, and their detection and quantification can be used in serologic diagnosis. T-antigen expressions were measured by the enzyme-linked lectin assay (ELLA) with peanut agglutinin (PNA) in the sera of patients with squamous cell carcinoma (SCC) of the uterine cervix from 286 patients. This study has a sensitivity of 80%, specificity of 82% and a positive predictive value of 93%. Quantification of the T-antigen may provide useful biochemical indices for clinical assessment of the tumor spread and invasiveness of disease in SCC of the uterine cervix. Moreover, the ELLA assay is cheap, easy to perform and reproducible in the prognosis and diagnosis of SCC of the uterine cervix.

Acrolein-induced toxicity--defective mitochondrial function as a possible mechanism.

Administration of acrolein (2.5 mg/kg body weight/day) to rats for 45 days depleted the glutathione level in liver, which triggered an imbalance in the antioxidant defense, resulting in lipid peroxidation. Enhanced lipid peroxidation damaged the membranous structure of mitochondria, which was indicated by the loss of lamellae, and increased the oxidation of exogenously added NADH. Loss in membrane integrity altered the activities of the tricarboxylic acid cycle enzymes and levels of cytochromes. Decreased rate of ADP-stimulated oxygen uptake, respiratory coupling ratio, and ATP synthesis-were also observed. We report that the acrolein-induced toxicity is mediated through the depletion of GSH leading to impairment of rat liver mitochondrial function.

Acute pulmonary toxicity of acrolein in rats--underlying mechanism.

Acute exposure of rats to acrolein (1 or 2 ppm) resulted in reduced levels of glutathione, ascorbic acid and alpha-tocopherol. The activities of catalase and glutathione peroxidase were reduced whereas an increase in the activities of superoxide dismutase was observed. This led to enhanced lipid peroxidation, which produced extensive lung damage as indicated by the elevated levels of the biochemical markers--angiotensin converting enzyme, lactate dehydrogenase, protein and lactate in the bronchoalveolar lavage.

Binding of Shigella to rat and human intestinal mucin.

Invasion of epithelial cells by Shigella is an early step in their pathogenesis. Adherence is generally presumed to be a prerequisite for invasion. This study examined the possibility of intestinal mucins serving as initial binding sites for clinical isolates of S. boydii and S. sonnei. The interactions of Shigella with rat and human small intestinal and colonic mucin were investigated. In solid phase binding assays, [35S] labelled Shigella did not show any preferential binding to rat/human small intestinal mucin or to rat colonic mucin. On the other hand, Shigella bound specifically to human colonic mucin in a concentration-dependent manner. This specific binding to human colonic mucin was not by weak hydrophobic interactions and could not be attributed to the presence of contaminating glycolipids in the mucin preparation. The human colonic mucin receptor was sensitive to periodate treatment suggesting the involvement of the carbohydrate portion of the mucin. Reduction and alkylation of mucin enhanced adherence probably by exposing buried binding sites. The monosaccharides present in mucins were ineffective as hapten inhibitors as was the lectin wheat germ agglutinin suggesting that the mucin receptor is a more complex one. This study identifies, for the first time, the presence of a specific Shigella-binding site on the carbohydrate portion of human colonic mucin, which is not present in rat colonic mucin or in rat/human small intestinal mucin.