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Biomedical subjects

A John

Publications and source records attributed to A John.

At least 37 records · Page 2Linked to original sources

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↗

IR and raman spectra of two layered aluminium phosphates Co(en)3Al3P4O16.3H2O and.

The FT IR and FT Raman spectra of Co(en)3Al3P4O16.3H2O (compound I) and [NH4]3[Co(NH3)6]3[Al2 (PO4)4]2.2H2O (compound II) are recorded and analysed based on the vibrations of Co(en)(3)3+, Co(NH3)(6)3+, NH4, Al-O-P, PO3, PO2 and H2O. The observed splitting of bands indicate that the site symmetry and correlation field effects are appreciable in both the compounds. In compound I, the overtone of CH2 deformation Fermi resonates with its symmetric stretching vibration. The NH4 ion in compound II is not free to rotate in the crystalline lattice. Hydrogen bonding of different groups is also discussed.

Aluminum Compounds↗

Vibrational spectra of four alkaline earth cyclo-hexaphosphates.

FT-IR and FT-Raman spectra of four alkaline earth (Mg, Ca, Sr and Ba) cyclo-hexaphosphates have been recorded and analysed. FT-Raman spectra of the deuterated analogues of these compounds are used to clear the ambiguity regarding the OH vibrations in the low frequency region. The spectra reveal that the P6O18(6) anion ring in all compounds have independent PO4 tetrahedra present in it. The P-O(P)and P-O(M')(M'-Mg, Ca, Sr and Ba) bonds become stronger as the cation size decreases. The P6O18(6-) anion ring is distorted in the Mg and Ca compounds. In the Sr and Ba compounds, free and hydrogen bonded water molecules of varying strength are present, whereas in Mg and Ca compounds no free water molecules exist. The POP bridge angle of the Mg, Ca and Sr compounds are estimated using the correlations between the POP bridge stretching frequencies and the bridge angle value.

Anions↗

Apparent failure of ultrasonography to detect adult worms of Brugia malayi.

Adult worms of Wuchereria bancrofti, or rather their characteristic movements (the 'filarial dance'), can now be detected in the scrotal lymphatics of microfilaraemic males, using ultrasonography. This ability has been used to delineate the lymphatic pathology of bancroftian filariasis, guide the surgical removal of the adult worms and, most importantly, assess the macrofilaricidal effects of antifilarial drugs. In the present study, the first report of the use of ultrasonography in brugian filariasis, 22 men (aged 18-62 years) with 60-2972 (median = 370) Brugia malayi microfilariae/ml blood were subjected to ultrasonography using a linear, 7.5-MHz probe. In addition, four other men (aged 19-35 years), with W. bancrofti microfilaraemia [28-524 (median = 234) microfilariae/ml], were similarly examined. Adult worms were not detectable in any of the patients with B. malayi parasitaemia but were detected in the scrotal lymphatics of two of the four individuals with W. bancrofti infection. The reasons for the failure to detect adult B. malayi and the limitations of ultrasound as a screening tool are examined. The results highlight the differences between the two species that cause most lymphatic filariasis and the need for rapid development of tools that can be used for the control of brugian lymphatic filariasis.

Adolescent↗

Two-year follow-up of the microfilaraemia of asymptomatic brugian filariasis, after treatment with two, annual, single doses of ivermectin, diethylcarbamazine and albendazole, in various combinations.

Repeated, single, oral doses of combinations of ivermectin, diethylcarbamazine (DEC) or albendazole are recognized as important tools for parasite control in lymphatic filariasis. In order to assess the effects of re-treatment using these combinations in Brugia malayi infections, 40 asymptomatic microfilaraemics were re-treated at the end of the first year, with an additional, single, dose of the combination they had previously received. They were then followed-up for another year. The subjects, of both sexes and aged 14-70 years, each received a two-drug combination: ivermectin (200 micrograms/kg) with DEC (6 mg/kg); ivermectin (200 micrograms/kg) with albendazole (400 mg); or DEC (6 mg/kg) with albendazole (400 mg). The kinetics of microfilarial clearance were similar to that seen during the first treatment, the members of the two groups given DEC having less intense microfilaraemias, 1 year after the re-treatment, than those given ivermectin with albendazole (P < 0.001 for each comparison). At this time, the two DEC groups also had a higher proportion of amicrofilaraemic individuals (22 of 26) than the ivermectin + albendazole group (three of nine). There were fewer adverse reactions in all the groups after re-treatment than seen after the first treatment. In countries such as India, where there is no co-endemicity of onchocerciasis or loiasis, the options for control programmes in areas where brugian filariasis is endemic are DEC alone or DEC in combination with ivermectin or albendazole. Where there is no access to ivermectin, transmission control must be based on DEC alone or in combination with albendazole.

Adolescent↗

Benchmarking in rehabilitation: comparing physiotherapy services.

This report presents outcome data from 3,176 consecutive prospective patients referred to physiotherapy for the treatment of soft tissue injuries. The results detailed here are part of a larger study collecting data from different NHS trusts in a benchmarking study. The Therapy Outcome Measure was used to collect data on each patient in four domains: Impairment, Disability/activity, Handicap/participation, and Distress/wellbeing on the entry and the exit from physiotherapy. The study concludes that patients do not have equal opportunity of accessing therapy for their specific condition according to their abilities and needs. Therapy provided in the Trusts did not produce similar changes in the patients' abilities and some dimensions appeared to improve more significantly in some locations. Furthermore this study would suggest that there are no common criteria for discharge of patients with similar conditions from physiotherapy across the Trusts as measured by the Therapy Outcome Measure.

Age Factors↗

Investigation of mucosal immunisation in pulmonary clearance of Moraxella (Branhamella) catarrhalis.

Moraxella (Branhamella) catarrhalis is a common cause of otitis media in children and respiratory infection in adults with chronic obstructive pulmonary disease. To identify immune responses that may facilitate the development of a mucosal vaccine, a mouse model to study pulmonary responses was established. Regimes involving intra-Peyer's patch, intratracheal and intranasal routes of immunisation with killed M. catarrhalis were investigated. A mucosal immunisation regime of a primary intra-Peyer's patch immunisation with an intratracheal boost resulted in significantly enhanced pulmonary clearance of bacteria compared to controls following an intratracheal challenge with live bacteria. Additional intratracheal boosts did not induce further enhancement of clearance. Intra-Peyer's patch immunisation alone, intratracheal and intranasal immunisations did not induce enhanced clearance. The levels of specific IgG and IgA in serum and bronchoalveolar lavage fluid correlated with pulmonary clearance. The present study showed that mucosal immunisation induced enhanced pulmonary clearance of M. catarrhalis following live bacterial challenge. This mucosal immunisation model has demonstrated that a mucosal vaccine, particularly an oral vaccine, would be feasible.

Animals↗

Treatment of the microfilaraemia of asymptomatic brugian filariasis with single doses of ivermectin, diethylcarbamazine or albendazole, in various combinations.

Several new chemotherapeutic tools are now available for the control of lymphatic filariasis. Combinations of single doses of antifilarial drugs are generally superior to single drugs. The efficacy and safety of albendazole in combination with diethylcarbamazine (DEC) or ivermectin, for the treatment of Brugia malayi infection, were investigated, for the first time, in an open, hospital-based study. Fifty-one asymptomatic microfilaraemics (with 108-4034 microfilariae/ml; median = 531) of both sexes and aged 14-70 years were randomly allocated to receive single-dose treatments of ivermectin (200 micrograms/kg) with diethylcarbamazine (DEC; 6 mg/kg), ivermectin (200 micrograms/kg) with albendazole (400 mg), DEC (6 mg/kg) with albendazole (400 mg), or albendazole (400 mg) alone. Albendazole alone had no effect on the microfilarial levels at the 1-year follow-up but both groups given DEC had significantly lower microfilaraemias (P < 0.015 and P < 0.02) than that given ivermectin with albendazole. Overall, 47%-64% of those given DEC but only 14% of those given ivermectin with albendazole appeared to be amicrofilaraemic 1 year post-treatment. The adverse reactions seen in the study were mild, transient and qualitatively similar to those seen earlier with ivermectin and DEC. The combination of DEC and albendazole, both well tested drugs, offers a new option for countries such as India where there is no onchocerciasis or loiasis and where ivermectin may not be immediately available. The direct and indirect effects of albendazole on intestinal helminths would be additional benefits.

Adolescent↗

Drug metabolizing enzyme systems in the houbara bustard (Chlamydotis undulata).

This study compared catalytic and immunochemical properties of drug metabolizing phase I and II enzyme systems in houbara bustard (Chlamydotis undulata) liver and kidney and rat liver. P450 content in bustard liver (0.34 +/- 0.03 nmol mg-1 protein) was 50% lower than that of rat liver (0.70 +/- 0.02 nmol mg-1 protein). With the exception of aniline hydroxylase activity, monooxygenase activities using aminopyrine, ethoxyresorufin and ethoxycoumarin as substrates were all significantly lower than corresponding rat liver enzymes. As found in mammalian systems the P450 activities in the bird liver were higher than in the kidney. Immunohistochemical analysis of microsomes using antibodies to rat hepatic P450 demonstrated that bustard liver and kidney express P4502C11 homologous protein; no appreciable cross-reactivity was observed in bustards using antibodies to P4502E1, 1A1 or 1A2 isoenzymes. Glutathione content and glutathione S-transferase (GST) activity in bustard liver were comparable with those of rat liver. GST activity in the kidney was 65% lower than the liver. Western blotting of liver and kidney cytosol with human GST isoenzyme-specific antibodies revealed that the expression of alpha-class of antibodies exceeds mu in the bustard. In contrast, the pi-class of GST was not detected in the bustard liver. This data demonstrates that hepatic and renal microsomes from the bustard have multiple forms of phase I and phase II enzymes. The multiplicity and tissue specific expression of xenobiotic metabolizing enzymes in bustards may play a significant role in determining the pharmacokinetics of drugs and susceptibility of the birds to various environmental pollutants and toxic insults.

Animals↗

Multiplicity and tissue specific expression of camel cytochrome P450(s).

The presence of multiple forms of the cytochrome P450 was demonstrated enzymatically in camel tissues using a variety of isoenzyme specific substrates and immunochemically using isoenzyme specific antibodies. The maximum catalytic activity using xenobiotics as substrate was observed in the liver followed by the kidney. However, lauric acid hydroxylation was found to be higher in the kidney than in any other tissues. Camel liver microsomal monooxygenase activity using aniline, aminopyrene, ethoxycoumarin, ethoxyresorufin and benzo(a)pyrene as substrates was comparable with those of rat and human livers. The activity of the enzymes in extrahepatic tissues of the camel was comparable with those of the rat extrahepatic tissues. The maximum expression of P450 protein was seen in the camel liver and kidney while the brain and intestine exhibited relatively low levels of expression. P450 expression in camel tissues appeared to be higher than in rat tissues. Immunohistochemical staining of P450 in the camel liver, kidney and brain confirmed the higher expression of P450 enzyme proteins in the liver and kidney as compared to other extrahepatic tissues. The maximum expression of P450 in the liver was observed in hepatocytes around the central vein and in the kidney it was observed in the proximal tubules. These results demonstrate that the multiple forms of P450s are differentially expressed in camel tissues and that the relative levels of expression are comparable with those of rat and human tissues. These observations may be important in understanding the differential susceptibility of camel tissues to the toxic/therapeutic effects of xenobiotics/drugs and environmental pollution.

Animals↗

Associations of angiotensinogen gene mutations with hypertension and myocardial infarction in a gulf population.

To date, the human angiotensinogen (AGT) gene and some of its variants represent the best examples of genetic influences that are involved in the determination of essential hypertension (EH) and associated cardiovascular diseases (CVDs). To assess the value of genotyping AGT in a genetically homogeneous population, we carried out a retrospective, case control study of variants M235T and T174M for putative correlations with CVDs among nationals from the United Arab Emirates (Emirati)--an ethnic group characterized by no alcohol intake and no cigarette smoking. We investigated a sample population of 229 Emirati (119 males and 110 females), comprising groups of controls and patients with clinical diagnoses of EH, left ventricular hypertrophy (LVH), ischaemic heart disease (IHD) and myocardial infarction (MI). M235T and T174M alleles were determined via assays based on the polymerase chain reaction. T174M showed no correlation with any of the four clinical entities included in this study. T235 alleles, however, occurred more frequently in the EH group and less frequently in the group of MI survivors. We also found that T235 allele frequencies decreased with age, indicating that in the Emirati population, T235 alleles are associated with a reduced life span and that this effect could occur through independent mechanisms underlying genetic susceptibilities to both EH and MI.

Adult↗