A simple technique to avoid inadvertent deep anchorage of surgical drains.
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Drainage↗
Biomedical subjects
A John
Publications and source records attributed to A John.
Differential modulation of growth and glutathione metabolism in cultured rat astrocytes by 4-hydroxynonenal and green tea polyphenol, epigallocatechin-3-gallate.
Oxidative stress has been implicated in the pathogenesis of cancer and prominent neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Apoptosis and cell cycle deregulation appear to be the mode of cell death in these disorders. Green tea polyphenol, epigallocatechin-3-gallate (EGCG) has been shown to be a potent antiinflammatory, apoptotic and cancer chemopreventive agent. 4-Hydroxynonenal (HNE), a by-product of lipid peroxidation (LPO), has been reported to induce apoptosis and inhibit growth in many cell systems including neuroglial cultures. We have studied both the dose and time dependent effects of HNE and EGCG on the viability of primary astrocyte cell cultures prepared from neonatal rats. HNE was found to be cytotoxic at a higher dose (0.1 mM) and markedly reduced (up to 80%) the astrocyte viability while EGCG did not appear to be cytotoxic under similar conditions. In addition, we have also studied the alterations in glutathione (GSH) and LPO levels and the activities of GSH metabolizing enzymes after treatment with HNE and EGCG. A 40% decrease in GSH level and a moderate increase in LPO were observed in HNE treated cells suggesting an increase in oxidative stress. HNE treatment caused a 50% decrease in GSH reductase and a 35% increase in GSH peroxidase activities. Although HNE treatment did not lead to any significant alterations in GSH-S-transferase (GST) activity, an increased expression of GST isoenzymes was seen following the exposure to HNE. EGCG treatment caused a significant increase in LPO even in the presence of elevated GSH content. In contrast to HNE, EGCG treatment resulted in a significant decrease (50%) in the activity and expression of GSTs. Treatment of astrocyte cultures with HNE, resulted in a severe impairment in mitochondrial respiration as measured by MTT exclusion assay, while treatment with EGCG had no effect on mitochondrial respiratory activity. Both HNE and EGCG were found to initiate apoptosis in astrocytes as measured by DNA fragmentation assay. However, HNE seems to be a stronger apoptotic and cytotoxic agent than EGCG. These results suggest that HNE and EGCG differentially modulate oxidative stress and regulate the growth and survival of astrocytes.
Aldehydes↗
The pharmacokinetics, safety and tolerability of the co-administration of diethylcarbamazine and albendazole.
The pharmacokinetics, safety and tolerability of single, oral doses of diethylcarbamazine (DEC) and albendazole, given alone or in combination, were investigated in a double-blind, randomized and placebo-controlled trial involving 42 amicrofilaraemic subjects living in an area of India where lymphatic filariasis is endemic. The subjects (34 males and eight females, aged 18-52 years and weighing 46-66.5 kg) were randomly allocated to one of the three drug groups. Fourteen were given just DEC (6 mg/kg), another 14 were given just albendazole (400 mg) and the remaining 14 were given both DEC (6 mg/kg) and albendazole (400 mg). Blood samples for pharmacokinetic study were collected at specified intervals before and after drug administration. Plasma concentrations of DEC and albendazole/albendazole sulphoxide were estimated using gas chromatography and HPLC, respectively. The safety and tolerability of the treatments were evaluated through clinical and laboratory assessments. Both the DEC and albendazole were well tolerated when given alone or in combination, no adverse events being observed. In all three treatment groups, the drugs were rapidly absorbed from the gastro-intestinal tract although there was marked inter-individual#10; variation. The pharmacokinetics of DEC, albendazole and albendazole sulphoxide were similar, whether each drug was given alone or in combination. These results indicate that there is no adverse pharmacokinetic or pharmacodynamic reason why DEC and albendazole should not be co-administered to control lymphatic filariasis.
Administration, Oral↗
Compound effects of point mutations causing campomelic dysplasia/autosomal sex reversal upon SOX9 structure, nuclear transport, DNA binding, and transcriptional activation.
Human mutations in the transcription factor SOX9 cause campomelic dysplasia/autosomal sex reversal. Here we identify and characterize two novel heterozygous mutations, F154L and A158T, that substitute conserved "hydrophobic core" amino acids of the high mobility group domain at positions thought to stabilize SOX9 conformation. Circular dichroism studies indicated that both mutations disrupt alpha-helicity within their high mobility group domain, whereas tertiary structure is essentially maintained as judged by fluorescence spectroscopy. In cultured cells, strictly nuclear localization was observed for wild type SOX9 and the F154L mutant; however, the A158T mutant showed a 2-fold reduction in nuclear import efficiency. Importin-beta was demonstrated to be the nuclear transport receptor recognized by SOX9, with both mutant proteins binding importin-beta with wild type affinity. Whereas DNA bending was unaffected, DNA binding was drastically reduced in both mutants (to 5% of wild type activity in F154L, 17% in A158T). Despite this large effect, transcriptional activation in cultured cells was only reduced to 26% in F154L and 62% in A158T of wild type activity, suggesting that a small loss of SOX9 transactivation activity could be sufficient to disrupt proper regulation of target genes during bone and testis formation. Thus, clinically relevant mutations of SOX9 affect protein structure leading to compound effects of reduced nuclear import and reduced DNA binding, the net effect being loss of transcriptional activation.
Abnormalities, Multiple↗
IL-13-induced airway hyperreactivity during respiratory syncytial virus infection is STAT6 dependent.
Airway damage and hyperreactivity induced during respiratory syncytial virus (RSV) infection can have a prolonged effect in infants and young children. These infections can alter the long-term function of the lung and may lead to severe asthma-like responses. In these studies, the role of IL-13 in inducing and maintaining a prolonged airway hyperreactivity response was examined using a mouse model of primary RSV infection. Using this model, there was evidence of significant airway epithelial cell damage and sloughing, along with mucus production. The airway hyperreactivity response was significantly increased by 8 days postinfection, peaked during days 10-12, and began to resolve by day 14. When the local production of Th1- and Th2-associated cytokines was examined, there was a significant increase, primarily in IL-13, as the viral response progressed. Treatment of RSV-infected mice with anti-IL-13 substantially inhibited airway hyperreactivity. Anti-IL-4 treatment had no effect on the RSV-induced responses. Interestingly, when IL-13 was neutralized, an early increase in IL-12 production was observed within the lungs, as was a significantly lower level of viral Ags, suggesting that IL-13 may be regulating an important antiviral pathway. The examination of RSV-induced airway hyperreactivity in STAT6(-/-) mice demonstrated a significant attenuation of the response, similar to the anti-IL-13 treatment. In addition, STAT6(-/-) mice had a significant alteration of mucus-producing cells in the airway. Altogether, these studies suggest that a primary factor leading to chronic RSV-induced airway dysfunction may be the inappropriate production of IL-13.
Animals↗
The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis.
Although a considerable amount of effort has been placed on discovering the etiologies of cancer, the majority of the basic cancer research existing today has focused on understanding the molecular mechanism of tumor formation and metastasis. Metastatic spread of tumors continues to be a major obstacle to successful treatment of malignant tumors. Approximately 30% of those patients diagnosed with a solid tumor have a clinically detectable metastasis and for the remaining 70%, metastases are continually being formed throughout the life of the tumor. Even after the tumor is excised, the threat of death is attributable to the metastasis that may occur through the remaining tumor cells. In addition, treating the metastasis often proves futile since metastasis often vary in size, composition, and anatomical location. New treatments blocking the formation of metastasis will provide greater chances of survival for cancer patients. One family of enzymes that has been shown over the years to play a role in tumor progression is the matrix metalloproteinase (MMP) family. The main function of MMPs, also known as matrixins, is degradation of the extracellular matrix physiologic function involving MMPs include wound healing, bone resorption and mammary involution. MMPs, however, also contribute to pathological conditions including rheumatoid arthritis, coronary artery disease, and cancer. Tumor cells are believed to utilize the matrix degrading capability of these enzymes to spread to distant sites. In addition, MMPs also are thought to promote the growth of these tumor cells once they have metastasized. This review will discuss the role of MMPs and their inhibitors in tumor invasion, angiogenesis and metastasis with special emphasis on the gelatinases, MMP-2 and MMP-9.
Humans↗
Caffeine-inhibitable control of the radiation-induced G2 arrest in L5178Y-S cells deficient in non-homologous end-joining.
The two L5178Y (LY) sublines bear a heterozygous Tp53 mutation that affects its transactivation function. LY-S (radiation-sensitive) cells are deficient in double strand break (DSB) repair by non-homologous end-joining (NHEJ) and do not express p21WAF1 (Cdkna1) either constitutively or after x-irradiation, in contrast to their radiation-resistant counterpart LY-R cells, which express p21WAF1 constitutively. Radiation-induced G2 arrest in LY-S cells is very long (11 h/Gy) but 2 mM caffeine treatment shortens it, decreases the fraction of G2 cells and increases the fraction of apoptotic cells. The treatment also increases the DNA damage that is estimated with the comet assay 18 h after irradiation with 5 Gy (ca. 23% of the initial value for x-rays and ca. 47% for x-rays plus caffeine). This indicates that either the repair has not been completed or the apoptotic DNA fragmentation has been initiated (or both). The same treatment applied to x-irradiated (5 Gy) LY-R cells (G2 arrest, 4 h/Gy) has no radiosensitising effect, induces no apoptosis and does not alter the amount of DNA damage left unrepaired (ca. 28%). The results are compatible with the assumption that inhibition of the Atm-dependent homologous recombination repair by caffeine, brings differential effects in LY sublines because of the defect of the alternative DNA repair system (NHEJ) in LY-S cells.
Animals↗
Hypotriglyceridemic and hypocholesterolemic effects of anti-diabetic Momordica charantia (karela) fruit extract in streptozotocin-induced diabetic rats.
Momordica charantia (karela) is commonly used as an antidiabetic and antihyperglycemic agent in Asian, Oriental and Latin American countries. This study was undertaken to investigate the effects of long term feeding (10 weeks) of M. charantia fruit extract on blood plasma and tissue lipid profiles in normal and streptozotocin (STZ)-induced Type 1 diabetic rats. The results show that there was a significant (P < 0.05) increase in plasma non-esterified cholesterol, triglycerides and phospholipids in STZ-induced diabetic rats, accompanied by a decrease in high density lipoprotein (HDL)-cholesterol. A moderate increase in plasma (LPO) product, malonedialdehyde (MDA), and about two-fold increase in kidney LPO was also observed in STZ-induced diabetic rats. The treatment of diabetic rats with M. charantia fruit extract over a 10-week period returned these levels close to normal. In addition, karela juice also exhibited an inhibitory effect on membrane LPO under in vitro conditions. These results suggest that M. charantia fruit extract exhibits hypolipidemic as well as hypoglycemic effects in the STZ-induced diabetic rat.
Animals↗
Vibrational analysis of Ag3(PO2NH)3, Na3(PO2NH)3 x H2O, Na3(PO2NH)3 x 4H2O,.
FT IR and FT Raman spectra of Ag3(PO2NH), (Compound 1), Na3(PO2NH)3 x H2O (Compound II), Na3(PO2NH)3 x 4H2O (Compound III), [C(NH2)3]3(PO2NH)3 x H2O (Compound IV) and (NH4)4(PO2NH)4 x 4H2O (Compound V) are recorded and analyzed on the basis of the anions, cations and water molecules present in each of them. The PO2NH- anion ring in compound I is distorted due to the influence of Ag+ cation. Wide variation in the hydrogen bond lengths in compound III is indicated by the splitting of the v2 and v3 modes of vibration of water molecules. The NH4 ion in compound V occupies lower site symmetry and exhibits hindered rotation in the lattice. The correlations between the symmetric and asymmetric stretching vibrations of P-N-P bridge and the P-N-P bond angle have also been discussed.
Hydrogen Bonding↗
FT-Raman, FT-IR and surface enhanced Raman scattering spectra of sodium salicylate.
FT-IR and FT-Raman spectra of sodium salicylate were recorded and analysed. Surface enhanced Raman scattering (SERS) spectrum was recorded is silver colloid. Comparisons of the SERS spectrum with the spectra in solution and of the solid sample are made. Sodium salicylate (an O donor ligand) is thought to adsorb in a somewhat 'tilted side on orientation' with respect to the silver surface.
Anti-Inflammatory Agents, Non-Steroidal↗
Intra-operative blood salvage in abdominal trauma: a review of 5 years' experience.
We performed a retrospective audit of 1235 patients presenting between 1992 and 1997, following the introduction of intra-operative blood salvage at our hospital. Twenty-two cases of severe abdominal trauma requiring emergency laparotomy and intra-operative blood salvage were identified. The impact of intra-operative blood salvage in aiding resuscitation and reducing demand on allogeneic blood supplies is discussed.
Abdominal Injuries↗
A trial to prepare biodegradable collagen-hydroxyapatite composites for bone repair.
This paper is a trial to prepare collagen-hydroxyapatite composites in vitro by an alternate immersion method. Collagen sponges of different biodegradabilities were prepared through chemical cross-linking of Type I collagen with glutaraldehyde (GA) at concentrations of 0.2, 1.0, and 2.0 wt%. The sponges were immersed at 37 degrees C in Tris-HCl-buffered solution containing 200 mM CaCl2 (pH 7.4) for 2 h and then in an aqueous solution of 120 mM Na2HPO4 (pH 9.3) for a 2 h further (one immersion cycle). The alternate immersion cycle was repeated for different times to obtain collagen-hydroxyapatite composites. The characterization of the resulting composites was performed by Fourier transform infrared spectroscopy (FT-IR). X-ray diffraction (XRD), and scanning electron microscopy (SEM). The weight of composites increased with an increase in immersion cycles and the rate of increase became greater with higher GA cross-linking levels for collagen sponge preparation. The pH of the phosphate solution decreased with the immersion cycle, which suggests H+ generation accompanied hydroxyapatite formation. Irrespective of the GA concentration and immersion cycle, every composite showed IR absorption bands attributable to phosphate and hydroxyl groups at 950-1100 or 550-650 and 3000-3500 cm(-1) and broad peaks specific to hydroxyapatite on the XRD charts. SEM study revealed small white clusters of hydroxyapatite interspersed uniformly on/in the collagen framework without any preferential orientation. The composite prepared from 0.2 wt% GA cross-linked collagen sponge which showed favourable characteristics was applied to a rat skull defect to evaluate its osteoconductivity as well as biodegradability. The formation of new bone tissue was histologically observed at the defect 12 weeks after application in marked contrast to the collagen sponge alone. The composite degraded without any inflammation reaction. It is concluded that the collagen-hydroxyapatite composite prepared by the present method is a biodegradable biomaterial of osteoconductivity applicable to bone repair.
Animals↗
Benchmarking can facilitate the sharing of information on outcomes of care.
Recent restructuring in the national health service (NHS) aimed to effect cultural and organisation changes that would ensure fair and equal access for service users to effective and efficient services. Clinical governance has been introduced as a means of delivering quality improvement. One element of this is the use of benchmarking to assess current process and outcome and to use comparative information to inform about current and best practice. The use of the Therapy Outcome Measure (TOM) (Enderby and John 1997) was investigated as an indicator to benchmark the outcomes of treatment for different client-groups and compare patterns of outcomes from different speech and language therapy (SLT) services. The study recruited eight SLT trust sites and ran for eighteen months. The TOM data was analysed to note similarities and differences in cases entering treatment, in the direction of change resulting from treatment, and on completing treatment. Variation was found on these points between cases with different disorders and across the trusts. TOM data could be used to provide a benchmark for a disorder against which services could make comparisons. However, for benchmarking to succeed there is a need for support and commitment from every level of an organisation.
Benchmarking↗
Spatial pattern learning in rats: control by an iterative pattern.
Rats searched in a matrix of vertical poles for food hidden on top of the poles. The only information available about the location of the food was the consistent spatial pattern of the baited poles, which was a checkerboard. This spatial pattern of hidden-food locations came to control the choices of poles made by the rats. The experiments ruled out the possibility that this control can be explained by the acquisition of simple response tendencies to move from pole to pole. Instead, this behavioral control of choices was attributed to the development of a representation of the checkerboard pattern of baited locations. Spatial pattern learning may have mechanisms in common with other forms of pattern learning.
Animals↗
Transcription of the interferon gamma (IFN-gamma )-inducible chemokine Mig in IFN-gamma-deficient mice.
MuMig or Mig (murine monokine induced by interferon gamma) is a CXC chemokine whose induction is thought to be strictly dependent on interferon gamma (IFN-gamma). Here we have studied the expression of this chemokine gene in various organs of mice infected with vaccinia virus. We have employed animals deficient in either IFN-gamma (IFN-gamma(-/-)), or receptors for IFN-alpha/beta, IFN-gamma, or both IFN-alpha/beta and IFN-gamma (DR(-/-)) to dissect out the role of interferons in the induction of Mig during the host response to virus infection. Our data show that Mig mRNA and protein are expressed in organs of vaccinia virus-infected IFN-gamma(-/-) mice, albeit at lower levels compared with infected, wild-type animals. In the DR(-/-) mice and in IFN-gamma(-/-) mice treated with a neutralizing antibody to IFN-alpha/beta, Mig mRNA transcripts were completely absent. Our data indicate that, in vaccinia virus-infected IFN-gamma(-/-) mice, Mig mRNA expression is mediated through the interaction between IFN-gamma responsive element 1 (gammaRE-1) and IFN-alpha/beta-induced STAT-1 complex referred to as IFN-gamma response factor 2 (gammaRF-2). Further, our findings support the view that gammaRF-2 is the IFN-alpha/beta induced STAT-1 complex, IFN-alpha-activated factor. We have found that, in the absence of IFN-gamma, IFN-alpha/beta are able to induce Mig in response to a viral infection in vivo.
Animals↗
Modulation of xenobiotic metabolism and oxidative stress in chronic streptozotocin-induced diabetic rats fed with Momordica charantia fruit extract.
We studied the long-term effects of streptozotocin-induced diabetes on tissue-specific cytochrome P450 (CYP) and glutathione-dependent (GSH-dependent) xenobiotic metabolism in rats. In addition, we also studied the effect of antidiabetic Momordica charantia (karela) fruit-extract feeding on the modulation of xenobiotic metabolism and oxidative stress in rats with diabetes. Our results have indicated an increase (35-50%) in CYP4A-dependent lauric acid hydroxylation in liver, kidney, and brain of diabetic rats. About a two-fold increase in CYP2E-dependent hepatic aniline hydroxylation and a 90-100% increase in CYP1A-dependent ethoxycoumarin-O-deethylase activities in kidney and brain were also observed. A significant increase (80%) in aminopyrene N-demethylase activity was observed only in rat kidney, and a decrease was observed in the liver and brain of diabetic rats. A significant increase (77%) in NADPH-dependent lipid peroxidation (LPO) in kidney of diabetic rats was also observed. On the other hand, a decrease in hepatic LPO was seen during chronic diabetes. During diabetes an increased expression of CYP1A1, CYP2E1, and CYP4A1 isoenzymes was also seen by Western blot analysis. Karela-juice feeding modulates the enzyme expression and catalytic activities in a tissue- and isoenzyme-specific manner. A marked decrease (65%) in hepatic GSH content and glutathione S-transferase (GST) activity and an increase (about two-fold) in brain GSH and GST activity was observed in diabetic rats. On the other hand, renal GST was markedly reduced, and GSH content was moderately higher than that of control rats. Western blot analyses using specific antibodies have confirmed the tissue-specific alterations in the expression of GST isoenzymes. Karela-juice feeding, in general, reversed the effect of chronic diabetes on the modulation of both P450-dependent monooxygenase activities and GSH-dependent oxidative stress related LPO and GST activities. These results have suggested that the modulation of xenobiotic metabolism and oxidative stress in various tissues may be related to altered metabolism of endogenous substrates and hormonal status during diabetes. The findings may have significant implications in elucidating the therapeutic use of antidiabetic drugs and management of Type 1 diabetes in chronic diabetic patients.
Animals↗
Differential induction of apoptosis in x-irradiated L5178Y sublines bearing p53 mutation.
We examined apoptosis and expression of p53, E2F-1, bax, bclx(L) and bc12 proteins in two L5178Y (LY) murine lymphoma sublines, LY-R and LY-S, which differ in radiosensitivity and double-strand break (DSB) repair. Both sublines are heterozygous for a p53 mutation in codon 170 that precludes the transactivation function. Accordingly, there is no G1/S arrest after irradiation. We found that there is no change in expression of E2F-1, bax, bclx(L) or bc12 proteins in both LY sublines after x-irradiation. LY-R cells do not constitutively express bc12, whereas both sublines show high bax content. Radiation induces delayed apoptosis to a greater extent in LY-S than in LY-R cells. The apoptosis can be seen 24 h after irradiation (2 Gy) of LY-S cells, with a maximum at 48 h. LY-R cells need 5 Gy and 72 h post-irradiation incubation to show marked apoptosis (identified by the TUNEL method). The reported observations support the assumption that differential radiosensitivity of LY sublines is associated with the induction of apoptosis that is not related to transactivation by p53 and is primarily related to differential DNA repair ability.
Animals↗
[Interventional therapy of aortic isthmus stenosis with concomitant thoracic aortic aneurysm with a stent graft].
A 23 year old male presented with hypertension and a systolic murmur. ECG and echo revealed signs of left ventricular hypertrophy. Aortography showed aortic coarctation (delta p max. 40 mmHg) in combination with an aneurysm originating from the coarcted segment distal from the origin of the left subclavian artery. Coarctation and aneurysm were treated using direct placement of a stent graft and subsequent balloon dilatation. On final aortography, the outline of the stented segment was smooth with good stent apposition and the aneurysm entry was closed. The residual gradient was 10 mmHg (max). Six months later, the patient has no symptoms and a blood pressure of 120/80 mmHg on both arms.
Adult↗