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Biomedical subjects

C E Bennett

Publications and source records attributed to C E Bennett.

At least 19 recordsLinked to original sources

Metformin reduces C-reactive protein but not complement factor C3 in overweight patients with Type 2 diabetes mellitus.

AIMS: To determine the influence of metformin treatment on plasma C-reactive protein (CRP) and complement factor C3. METHODS: A double-blind, placebo-controlled trial of metformin in patients with poorly controlled Type 2 diabetes mellitus and body mass index > 25 kg/m2. CRP and C3 were analysed in stored plasma samples by in-house ELISAs. Patients attended two baseline visits before randomization and subsequently attended at 3, 6, 12 and 24 weeks post randomization. All patients gave informed consent according to a protocol approved by the Leeds Teaching Hospitals Research Ethics Committee. RESULTS: Baseline CRP in the patients randomized to placebo [1.33 (0.79, 2.25) mg/l] and metformin [1.24 (0.89, 1.71) mg/l] were similar (P = 0.8). Baseline CRP correlated with baseline C3 (r = 0.366) and HbA1c (r = 0.327). The difference in ratios of CRP levels at each visit to baseline between placebo- (n = 16) and metformin-treated (n = 26) subjects was significantly different at the 12-week (P = 0.002) and 24-week (P = 0.03) visits. The difference in CRP ratios between the two treatment groups remained significant after accounting for glycaemic control at both visits (P = 0.001 and P = 0.003, respectively). Baseline C3 was correlated with CRP. Baseline C3 was lower in the placebo-treated group [0.97 (0.88, 1.05) mg/ml] compared with the metformin-treated group [1.09 (1.02, 1.17) mg/ml, P = 0.03]. There was no difference in the mean change in C3 at any visit from baseline between placebo- and metformin-treated groups. CONCLUSION: Metformin may have a specific interaction with mechanisms involved in CRP synthesis or secretion, not directly related to improved insulin sensitivity and dampening of chronic inflammation.

C-Reactive Protein↗

Studies on the synthesis of landomycin A: synthesis and glycosidation reactions of L-rhodinosyl acetate derivatives.

An efficient, eight-step synthesis of L-rhodinosyl acetate derivative 3 is described. The synthesis originates from methyl (S)-lactate and involves a highly stereoselective, chelate-controlled addition of allyltributylstannane to the lactaldehyde derivative 7. The beta-anomeric configuration of 3 was established with high selectivity by acetylation of the pyranose precursor with Ac(2)O and Et(3)N in CH(2)Cl(2). Preliminary studies of glycosidation reactions of 3 and L-rhodinosyl acetate 10 containing a 3-O-TES ether revealed that these compounds are highly reactive glycosidating agents and that trialkylsilyl triflates are effective glycosylation promoters. The best conditions for reactions with 15 as the acceptor involved use of diethyl ether as the reaction solvent and 0.2 equiv of TES-OTf at -78 degrees C. However, the TES ether protecting group of 10 proved to be too labile under these reaction conditions, and mixtures of 16a, 17, and 18a are obtained in reactions of 10 and 15. Disaccharide 17 arises via in situ cleavage of the TES ether of disaccharide 16a, while trisaccharide 18a results from a glycosidation of in situ generated 17 (or of 16a itself) with a second equivalent of 10. These problems were largely suppressed by using 3 with a 3-O-TBS ether protecting group as the glycosyl donor and 0.2 equiv of TES-OTf as the reaction promoter. Attempts to selectively glycosylate the C(3)-OH of diol acceptors 20 or 28 gave a 70:30 mixture of 21 and 22 in the reaction of 20 and a 43:27:30 mixture of regioisomeric trisaccharides 29 and 30 and tetrasaccharide 31 from the glycosidation reaction of 28. However, excellent results were obtained in the glycosidation of differentially protected disaccharide 34 using 1.5 equiv of 3 and 0.05 equiv of TBS-OTf in CH(2)Cl(2) at -78 degrees C. The latter step is an important transformation in the recently reported synthesis of the landomycin A hexasaccharide unit.

Aminoglycosides↗

Fasciola hepatica: surfaces involved in movement of miracidia and cercariae.

Rapid freezing and substitution with fixative prior to scanning electron microscopy was used to demonstrate the pattern of beat and recovery of the cilia of free swimming miracidia of Fasciola hepatica. There were stages of dexioplectic metachronal co-ordination and the power stroke was approximately 15 degrees anticlockwise from the anterior-posterior axis. Around the circumference of the body of the miracidia there were approximately 12 metachronal waves of power and recovery. Free-swimming cercariae were recorded by time-lapse photography and, after conventional fixation, by scanning electron microscopy. Cercarial tail-beats were to the posterior of the body in the lateral plane at a rate of 8 Hz. The tail has paired lateral ridges positioned to act as leading edges. There is an array of 32 sensory papillae on the mid-ventral surface of the tail. The tegument of the most distal part of the tail is described: it is free of sensory endings and the surface shows a spiral pattern.

Animals↗

2-Deoxy-2-iodo- and 2-deoxy-2-bromo-alpha-glucopyranosyl trichloroacetimidates: highly reactive and stereoselective donors for the synthesis of 2-deoxy-beta-glycosides.

[formula: see text] 2-Deoxy-2-iodo- and 2-deoxy-2-bromoglucopyranosyl trichloroacetimidates 8-10 and 22 are extremely useful precursors of 2-deoxy-beta-glycosides. These reactive glycosyl donors undergo highly stereoselective glycosidation reactions at -78 degrees C with a range of glycosyl acceptors using TBS-OTf as the activating agent. beta-Glycosides are obtained with > or = 19:1 selectivity in six of the seven examples reported herein.

Acetamides↗

Iodoacetoxylation of glycals using cerium(IV) ammonium nitrate, sodium iodide, and acetic acid: stereoselective synthesis of 2-deoxy-2-iodo-alpha-mannopyranosyl acetates.

[formula: see text] The reactions of glycals with ceric(IV) ammonium nitrate and sodium iodide in the presence of acetic acid provides 2-deoxy-2-iodo-alpha-mannopyranosyl acetates with good stereoselectivity. In the majority of the cases examined, the selectivity was considerably better than that from reactions using N-iodosuccinimide and HOAc.

Acetates↗

Light reflection rheography: an effective non-invasive technique for screening patients with suspected deep venous thrombosis.

Light reflection rheography is a simple non-invasive technique for assessing venous function in the leg. One hundred and twenty-four patients referred for venography with a clinically suspected deep venous thrombosis were investigated by light reflection rheography to determine the accuracy of the technique in diagnosing acute thrombosis. In half of the patients venography confirmed a deep venous thrombosis. Light reflection rheography had a sensitivity of 92 per cent and a specificity of 84 per cent in detecting acute thrombosis. The technique had a negative predictive value of 92 per cent in selecting those patients with no thrombosis. Light reflection rheography can be performed at the bedside or in the radiography department which makes it a suitable technique for screening patients with suspected deep venous thrombosis.

Female↗

Retrograde femoral angioplasty: a new technique.

Percutaneous transluminal angioplasty cannot be used for lesions of the superficial femoral artery when the origin of the vessel is occluded. A new technique, retrograde femoral angioplasty, is described in which angioplasty is performed from below via the exposed popliteal artery. In four out of six patients retrograde femoral angioplasty was successfully completed, and three of the four vessels remain patent up to 1 year later. The method provides an alternative to the femoropopliteal bypass graft in some patients.

Angioplasty, Balloon↗

Small bowel function after aortic surgery.

One cause of post-operative morbidity in the elective repair of abdominal aortic aneurysms is the development of a paralytic or 'adynamic' ileus. In a series of 20 consecutive patients undergoing such a procedure, the maintenance of small bowel motility and absorptive capacity in the immediate post-operative period was assessed using barium sulphate and xylose passed down a naso-duodenal tube sited at the time of surgery. This simple study demonstrated that small bowel function was preserved in all cases, and hence that patients could be fed enterally via naso-duodenal tube (in particular using very low residue formulae) rather than using costly parenteral regimens, should an ileus persist.

Aorta, Abdominal↗

Bile leaks after simple cholecystectomy.

Drains after cholecystectomy are used commonly to avoid biliary leaks and subsequent peritonitis. Thirty-five patients who had had cholecystectomy without drainage underwent 99mTc-labelled dimethylphenylcarbamoylmethyliminodiacetic acid (HIDA) and ultrasound scans the morning after surgery. Biliary leaks detected by positive HIDA scans occurred in 11 patients. Subhepatic fluid collections were seen on 20 ultrasound scans. There was no relation between biliary leaks and subhepatic collections. Many of the collections were not seen on the HIDA scan, suggesting that they contained blood and not bile. Many of the patients with bile leaks showed no fluid collection. Clinical complications were few and evenly distributed between those with positive and negative scans. We conclude that bile leaks are not an occasional event but occur after 31 per cent of undrained cholecystectomies and that these bile leaks remain clinically unimportant.

Bile↗

Effects of ethyl alcohol on human peripheral lymphocytes.

Chronic alcoholics are more susceptible to infection and have increased incidences of certain types of carcinomas. One explanation for this may be suppressed immune responses secondary to ethyl alcohol consumption. This project was initiated to study the effect of ethyl alcohol on lymphocyte responses in vitro by monitoring tritiated thymidine uptake. Lymphocytes were incubated in the presence of phytohemagglutinin-P, concanavalin A, and pokeweed mitogen. The response of normal lymphocytes was noted after mitogen stimulation in the presence of ethyl alcohol in graded doses. Ethyl alcohol levels greater than or equal to 50 mg/dL suppressed tritiated thymidine uptake of normal lymphocytes for phytohemagglutinin-P and concanavalin A. Since ethyl alcohol exposure in concentrations consistent with blood levels that may be attained during routine ingestion significantly decreased lymphocyte blastogenesis, it is speculated that chronic ethyl alcohol ingestion may alter immune surveillance sufficiently to be responsible in part for the increased incidence of infection and/or neoplasms seen in alcoholic subjects.

Adult↗

DNA and protein synthesis in normal and transformed lymphocytes exposed to abrin.

The dose dependent effects of abrin, a toxic D-galactose binding plant lectin, on 3H-TdR and 14C-leucine uptake are studied in normal and Epstein Barr Virus (EBV) transformed lymphocyte cultures. Results show that while abrin is highly toxic to both the DNA and protein synthesis in EBV lymphocytes, some toxicity to the normal cells is also seen. It is postulated that lymphocyte DNA synthesis is affected by ribosomal shutdown induced by the abrin.

Abrin↗

Studies on the toxicity and binding kinetics of abrin in normal and Epstein-Barr virus-transformed lymphocyte culture-I. Experimental results - 4.

The effects of treatment with varying doses of abrin, a D-galactose binding lectin, on DNA and protein synthesis of normal and Epstein-Barr virus (EBV)-transformed lymphocytes have been previously investigated. Using data on EBV-transformed lymphocyte cell density as a function of both time and dose of abrin, the authors introduced the concept of self- and cross-coupling metabolic variables as a means of understanding how abrin affected DNA and protein uptake. In this paper, the self-coupling constant is studied in more detail and the relationship between DNA and protein synthesis is further expanded. We find that there is a significant linear relationship between DNA and protein synthesis in normal lymphocyte culture as measured by abrin interaction in the culture. We further find that there is a much stronger relationship between these variables in EBV-transformed lymphocyte culture. This relationship is further examined, and possible analytic equations are expressed.

Abrin↗

Demonstration of juvenile-specific antigens of Fasciola hepatica.

A hyperimmune serum was raised in rabbits against soluble antigens of Fasciola hepatica metacercariae. This was subsequently absorbed with antigens from adult flukes and examined by immunoelectrophoresis (IEP) and by an indirect fluorescent antibody test (IFAT). When the absorbed antiserum was tested with F. hepatica metacercarial homogenate and adult homogenates by IEP, three distinct arcs appeared against the metacercarial homogenate and none against the adult homogenate. When tested by IFAT against a developmental series of flukes obtained from mice, the absorbed antiserum was positive on surfaces of whole flukes up to 4 days postinfection (PI) and on the tegument of sectioned flukes up to 7 days PI. Thus juvenile-specific antigens were demonstrated in the tegument of young (up to 7 days in mice) F. hepatica.

Animals↗

Studies on the toxicity and binding kinetics of abrin in normal and Epstein Barr virus-transformed lymphocyte culture-I: experimental results - 1.

The effects of treatment with varying doses of abrin, a D-galactose binding lectin, on DNA and protein synthesis of normal and Epstein Barr virus-transformed lymphocytes have been investigated. Activation, stimulation and relative toxicity factor indices are studied as well as possible relationships between the DNA and protein synthesis rates, as measured by simultaneous 3H-TdR and 14C-leucine uptake.

Abrin↗

Studies on toxicity and binding kinetics of abrin in normal and Epstein Barr virus-transformed lymphocyte culture-I: experimental results - 2.

The effects of treatment with varying doses of abrin, a D-galactose binding lectin, on DNA and protein synthesis of normal and Epstein Barr virus-transformed lymphocytes have been investigated. Studies of activation and stimulation indices, as well as two new indices; the metabolic self and cross-coupling indices, lead to the prediction that there are three morphologically distinct subpopulations of EBV-transformed lymphocytes with different abrin binding site numbers. This conclusion is supported by SEM morphological differences.

Abrin↗