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1.
Hernia ; 27(5): 1085-1093, 2023 10.
Article in English | MEDLINE | ID: mdl-37093340

ABSTRACT

INTRODUCTION: Evaluating groin pain still evades many clinicians at times as they have difficulty determining the cause of pain when no true hernia exists. This study's aim was to evaluate a simple and novel scoring system which is reproducible, to help determine whether conservative measures or surgery is recommended for the management of groin pain attributable to inguinal disruption. MATERIAL & METHODS: A retrospective analysis of all patients from 2018 to 2020 that underwent surgery or conservative management for inguinal disruption with at least a 1-year follow-up were evaluated. The scoring system is based on MRI and ultrasound imaging as well as clinical findings, with scores given from - 2 to + 2 based on the defined findings listed. A maximum total of four points scored for each assessment was used. Sensitivity and specificity analysis was conducted for each potential score cut off point. RESULTS: A total of 172 patients were evaluated with 33 patients (19%) undergoing conservative management and 139 patients (81%) undergoing surgery. The median SPoRT score for the surgery group was 2.0 (1.0, 3.0), and - 1.0 (- 3.0, 0.0) in the physiotherapy group which was a significant difference (p < 0.001). An optimal cut off of ≤ 0 for physio and ≥ 1 for surgery was established, yielding a sensitivity of 90.9% (95% CI 75.7%-98.1%), a specificity of 89.2% (95% CI 82.8%-93.8%) and an area under the curve (AUC) of 0.936 (95% CI 0.874-0.997). DISCUSSION: SPoRT score of ≤ 0 can recommend a patient should undergo conservative measures or physiotherapy as a mainstay of treatment with a score of ≥ 1 recommending surgery. Further validation of the score is necessary.


Subject(s)
Groin , Hernia, Inguinal , Humans , Groin/surgery , Retrospective Studies , Hernia, Inguinal/surgery , Herniorrhaphy/methods , Pelvic Pain/surgery
2.
Surg Endosc ; 35(8): 4371-4379, 2021 08.
Article in English | MEDLINE | ID: mdl-32909207

ABSTRACT

BACKGROUND: Surgery has a recognised role in the treatment of 'sportsman's groin'. This study hypothesises that elite athletes have a superior advantage in both pre- and post-op rehabilitation and therefore will present and resume sporting activities quicker. METHODS: A retrospective analysis on a secure database of athletes presenting with groin pain that underwent surgery for 'inguinal disruption'. All data were explored via appropriate descriptive statistics and comparisons made between elite and amateur athletes. RESULTS: All patients were male (n = 144). The median age 33 years (range 14-72). The median return to sporting activity was 4.5 weeks (range 2.0-16.0) with one amateur athlete being unable to return to sporting activity. Using the mean of both sides, a comparison of VAS pain scores at pre-operative and 1 month post-operative time points showed a significant reduction (p < 0.001). Comparing 'elite' versus 'amateur' athletes, significant differences were seen in patient age (median 26 vs 40 years; p < 0.001), lead time to clinic presentation (median 62.0 vs 111.5 days; p = 0.004), and time to return to sporting activity (4 vs 5 weeks; p = 0.019). Additional MRI findings within the groin girdle were found in 89 patients (66.4%) and 34 patients (23.6%) had an MRI finding within the adductor tendon. CONCLUSION: The Manchester Groin Rrepair is an effective surgical management for 'inguinal disruption'. Elite athletes present quicker and return to sport sooner. Given the prevalence of other findings, a multidisciplinary approach to the 'sportsman's groin' is required.


Subject(s)
Athletic Injuries , Hernia, Inguinal , Adolescent , Adult , Aged , Athletes , Athletic Injuries/surgery , Groin/injuries , Groin/surgery , Hernia, Inguinal/surgery , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
3.
Eur J Trauma Emerg Surg ; 44(1): 63-70, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28204851

ABSTRACT

BACKGROUND: Over the last decade trauma services have undergone a reconfiguration in England and Wales. The objective is to describe the epidemiology, management and outcomes for liver trauma over this period and examine factors predicting survival. METHODS: Patients sustaining hepatic trauma were identified using the Trauma Audit and Research Network database. Demographics, management and outcomes were assessed between January 2005 and December 2014 and analysed over five, 2-year study periods. Independent predictor variables for the outcome of liver trauma were analysed using multiple logistic regression. RESULTS: 4368 Patients sustained hepatic trauma (with known outcome) between January 2005 and December 2014. Median age was 34 years (interquartile range 23-49). 81% were due to blunt and 19% to penetrating trauma. Road traffic collisions were the main mechanism of injury (58.2%). 241 patients (5.5%) underwent liver-specific surgery. The overall 30-day mortality rate was 16.4%. Improvements were seen in early consultant input, frequency and timing of computed tomography (CT) scanning, use of tranexamic acid and 30-day mortality over the five time periods. Being treated in a unit with an on-site HPB service increased the odds of survival (odds ratio 3.5, 95% confidence intervals 2.7-4.5). CONCLUSIONS: Our study has shown that being treated in a unit with an on-site HPB service increased the odds of survival. Further evaluation of the benefits of trauma and HPB surgery centralisation is warranted.


Subject(s)
Digestive System Surgical Procedures , Emergency Medicine , Length of Stay/statistics & numerical data , Liver/injuries , Wounds, Nonpenetrating/surgery , Wounds, Penetrating/surgery , Adult , Antifibrinolytic Agents/therapeutic use , Digestive System Surgical Procedures/mortality , Emergency Medicine/standards , England/epidemiology , Female , Health Services Research , Hospital Mortality , Humans , Injury Severity Score , Liver/surgery , Logistic Models , Male , Outcome Assessment, Health Care , Survival Analysis , Tranexamic Acid/therapeutic use , Wales/epidemiology , Wounds, Nonpenetrating/mortality , Wounds, Penetrating/mortality
4.
J Hosp Infect ; 91(2): 171-5, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26184663

ABSTRACT

BACKGROUND: This article reports a historical outbreak of Salmonella hadar in a maternity setting. The outbreak occurred following admission of an infected index case, with transmission to 11 other individuals over a three-month period in a maternity and neonatal unit. METHODS: Despite rigorous assessment of clinical practices, screening of patients and staff, and review of disinfection and sterilization policies, the outbreak was difficult to control. This possibly reflects the capacity of S. hadar to survive well in the environment, and cause prolonged and asymptomatic carriage with intermittent shedding. FINDINGS: It is likely that the index case was a mother who had contracted infection after eating suspect food. Additionally, infection may have been perpetuated by shared use of tubes of yellow soft paraffin for lubrication of digital rectal thermometers. CONCLUSION: This outbreak emphasizes the difficulties in controlling outbreaks of S. hadar infection in an obstetric/neonatal setting, and also emphasizes the importance of early stool sampling in any patient with diarrhoeal symptoms.


Subject(s)
Cross Infection/epidemiology , Diarrhea/epidemiology , Disease Outbreaks , Salmonella Infections/epidemiology , Salmonella enterica/isolation & purification , Adult , Bacterial Shedding , Carrier State/epidemiology , Carrier State/microbiology , Cross Infection/microbiology , Diarrhea/microbiology , Female , Hospitals, Maternity , Humans , Infant, Newborn , Infection Control/methods , Male , Salmonella enterica/classification
5.
J Agric Food Chem ; 60(48): 12036-43, 2012 Dec 05.
Article in English | MEDLINE | ID: mdl-23151273

ABSTRACT

Soybean trypsin inhibitor (STI) is a known antinutrient and food allergen present in soybean. γ-Radiation has the potential to inactivate the TI protein. However, a systematic study on the influence of different moisture levels during γ radiation on structure and function of the molecule has not been reported. Pure STI was irradiated up to 200 kGy, in dry state, with 50% moisture and in aqueous solution. The radiation damage in molecular structure was assessed using, SDS-PAGE, size exclusion chromatography, fluorescence measurement, and circular dichroism, while functional damage was assessed by the TI assay. In aqueous solution, both the structure and function of TI were almost destroyed at the 10 kGy dose. While with 50% moisture and in dry state, the loss in functional and structural attributes was discernible only at 30 and 100 kGy, respectively. The TI activity was found to be unaffected in dry and soaked seeds of soybean as well as other legumes up to irradiation doses of 100 and 50 kGy, respectively.


Subject(s)
Soybean Proteins/chemistry , Circular Dichroism , Dose-Response Relationship, Radiation , Electrophoresis, Polyacrylamide Gel , Fluorescence , Food Irradiation , Gamma Rays , Hydrophobic and Hydrophilic Interactions , Protein Conformation , Seeds/chemistry , Seeds/radiation effects , Soybean Proteins/pharmacology
6.
Euro Surveill ; 17(9)2012 Mar 01.
Article in English | MEDLINE | ID: mdl-22401562

ABSTRACT

Three isolates of Neisseria gonorrhoeae have been identified in Scotland in 2010 and 2011, which lack sequences in the porA pseudogene commonly used as the target for confirmatory gonorrhoea polymerase chain reaction assays. Two isolates were clustered temporally and geographically and have the same sequence type and porA sequence. A similar strain was reported in Australia during early 2011. The other Scottish isolate was identified separately and is different in sequence type and porA sequence.


Subject(s)
Neisseria gonorrhoeae/genetics , Neisseria gonorrhoeae/isolation & purification , Porins/genetics , Porins/isolation & purification , Base Sequence , Gonorrhea/diagnosis , Gonorrhea/genetics , Humans , Male , Molecular Sequence Data , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Scotland , United Kingdom
8.
Bioresour Technol ; 99(15): 6934-40, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18343658

ABSTRACT

Protein hydrolysate was prepared from poultry viscera by a procedure involving autolysis for 6h at pH 2.8 and 55 degrees C followed by heat inactivation, filtration and drying. Recovery of nitrogen in the product was 87%. The process reduced the viable count of bacteria by 5-6logcfu/g. The product contained 84% protein, 6.5% ash and 8.8% moisture. Peptide analysis by gel filtration chromatography showed size in the range of 0.5-5kDa. RPHPLC exhibited the presence of hydrophilic peptides in higher concentration than that in trypsin digest of casein. Protein hydrolysate exhibited presence of all essential amino acids in comparison with reference protein except for methionine and threonine. The product possesses excellent solubility (>93%) over a pH range of 1-12. Efficacy of the product as a bacteriological media or feed supplement is discussed.


Subject(s)
Proteins/metabolism , Animals , Hydrolysis , Poultry , Solubility
9.
Int J Clin Pract ; 59(11): 1368-70, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16236094

ABSTRACT

Haemorrhage can be a lethal complication of severe acute pancreatitis. Management includes identification and control of the source of bleeding and supportive therapy such as blood transfusion. Individuals who refuse transfusion on the grounds of religious belief can provide a further major challenge. The management in these individuals can be focused from the outset with a strategy that aims to avert anaemia and transfusion. This article reports a case of severe acute pancreatitis in a woman of the Jehovah's Witness faith. The episode was complicated by infected pancreatic necrosis requiring surgical intervention. Careful strategic planning is critical to the management of severe acute pancreatitis in patients of the Jehovah's Witness faith. In this case, acute pancreatitis complicated by infected necrosis was successfully managed by the use of preoperative erythropoietin, venesection using paediatric blood vials, meticulous intraoperative attention to haemostasis and the use of adjunctive intraoperative techniques such as argon diathermy.


Subject(s)
Jehovah's Witnesses , Pancreatitis, Acute Necrotizing/surgery , Religion and Medicine , Adult , Blood Transfusion , Contraindications , Female , Hemostasis, Surgical/methods , Humans
10.
Bioresour Technol ; 96(11): 1276-84, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15734315

ABSTRACT

Data on the exhaustive degradation of chicken intestinal proteins by endogenous proteases, which could be utilized as a means to prepare protein hydrolysate, is reported in the present paper. Chicken intestine possesses proteolytic activities (cathepsin B, D, H, L, aminopeptidases and alkaline proteases) comparable to that in organ tissues like liver and spleen, which could degrade the tissue proteins extensively. The autolytic degradation was found to be optimum at pH 2.5 and 60 degrees C. Analysis by SDS-PAGE showed a time dependent degradation of proteins to low molecular weight (<10 kDa) products. Kinetic studies employing specific inhibitors indicated that the degradation (90-94%) of proteins at acidic pH is governed largely by pepstatin sensitive proteases. The acidic extract of the tissue was found to hydrolyse albumin, casein and soybean proteins efficiently. Results point to the possible application of tissue autolysis for obtaining protein hydrolysates from chicken intestine. Chicken intestine could also serve as a potential source of much needed proteolytic enzymes for food and pharmaceutical applications.


Subject(s)
Autolysis/metabolism , Bioreactors , Chickens/metabolism , Enzymes/metabolism , Intestines/enzymology , Protein Hydrolysates/biosynthesis , Proteins/metabolism , Animals , Electrophoresis, Polyacrylamide Gel , Hydrogen-Ion Concentration , Kinetics , Soybean Proteins/isolation & purification , Soybean Proteins/metabolism , Temperature
11.
Indian J Clin Biochem ; 19(2): 84-90, 2004 Jul.
Article in English | MEDLINE | ID: mdl-23105461

ABSTRACT

To purify and evaluate the molecular changes associated with an aspartic protease (Cathepsin D) in human semen from infertile subjects. Cathepsin D was purified from normo-, oligo- and azoospermic semen, by a procedure involving detergent solubilisation, affinity chromatography and gel filtration chromatography. The enzyme from normo-, oligo- and azoospermic samples was purified 86, 60 and 44 fold respectively. The purified enzyme appeared as a single band on SDS as well as on native PAGE irrespective of the pathological conditions. The molecular weight of Cathepsin D from oligospermic and normospermic samples was 40 kDa while that of azoospermic sample was found to be 43 kDa. The enzyme was inhibited by pepstatin while other proteinase inhibitors and metal ions did not have any effect. Purified Cathepsin D from azoospermic sample differs from normospermia and oligospermia.

12.
Arthroscopy ; 17(7): E30, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11536110

ABSTRACT

A case of arthroscopic identification and removal of a shotgun pellet from the elbow joint is presented. The pellet had entered the soft tissues over the dorsum of the joint and had migrated to an intra-articular position, causing interference with movement of the elbow. Arthroscopy of the joint was performed using standard portals. The pellet was discovered anterior to the coronoid process of the ulna in the anterior recess of the joint and was removed using forceps. At follow-up, the patient reported a symptom-free elbow with full range of movement.


Subject(s)
Arthroscopy , Elbow Joint/surgery , Foreign Bodies/surgery , Wounds, Gunshot/surgery , Elbow Joint/diagnostic imaging , Humans , Middle Aged , Radiography , Elbow Injuries
13.
J Anal Toxicol ; 24(6): 438-41, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10999350

ABSTRACT

An improved method for the simultaneous determination of cocaine and its metabolites, benzoylecgonine (BE), norcocaine, and ecgoninemethylester (EME), in rat plasma and urine is described. Following derivatization of EME to p-fluorococaine, chromatography was performed on two high-performance liquid chromatography (HPLC) columns in series (5-microm spheric C8 and 5-microm cyanopropyl) using a mobile phase containing acetonitrile/HPLC water/trifluoroacetic acid (28:72:0.1) with bupivacaine as an internal standard. Quantitation limits were 25 ng/mL for cocaine, BE, and norcocaine and 50 ng/mL for EME using 300-500 microL rat plasma and 500 microL of rat urine. The assay was linear from the limit of quantitation to 2000 ng/mL for cocaine and its metabolites in both plasma and urine samples. Because this method uses a small amount of sample (300 microL plasma or 500 microL of urine), it is applicable to study of the pharmacokinetics and disposition of cocaine and its major metabolites.


Subject(s)
Chromatography, High Pressure Liquid/methods , Cocaine/analogs & derivatives , Cocaine/analysis , Substance Abuse Detection/methods , Animals , Cocaine/pharmacokinetics , Male , Rats , Rats, Sprague-Dawley , Sensitivity and Specificity
14.
Life Sci ; 65(12): 1317-28, 1999.
Article in English | MEDLINE | ID: mdl-10503947

ABSTRACT

We have compared the pharmacokinetics of bolus dose cocaine administration with that of its three most important metabolites; norcocaine, ecgonine methylester, and benzoylecgonine and assessed whether kinetics are dose dependent at two equimolar doses equivalent to cocaine hydrochloride 2.5 and 5 mg/kg respectively. Forty-nine male Sprague-Dawley rats were randomly divided into 8 groups to receive i.v. either high (14.7 umol/kg) (HI) or low (7.3 umol/kg) (LO) bolus doses of cocaine or one of its metabolites. Arterial blood samples for cocaine and metabolite analysis were taken repetitively over the next 3 h. Equimolar bolus doses of these congeners showed biexponential plasma concentration decay curves which were fitted to a two compartment model and subjected to noncompartmental analysis. The plasma concentration time profiles were significantly different for the HI and LO doses administered for each congener. The elimination half-lives of cocaine and norcocaine were similar (28-33 min), that for ecgonine methylester (60-71 min) was approximately twice this and for benzoylecgonine was 40-44 min. Cocaine clearance (155-158 ml/kg/min) was found to be in the range found in other rat studies. Ecgonine methylester clearance and benzoylecgonine clearance were found to be one quarter and one eighth of this value respectively. The pharmacokinetic profile of these congeners was not dose dependent when the two doses administered were compared.


Subject(s)
Cocaine/analogs & derivatives , Cocaine/pharmacokinetics , Animals , Dose-Response Relationship, Drug , Half-Life , Male , Rats , Rats, Sprague-Dawley
15.
J Pharm Pharmacol ; 51(6): 679-84, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10454044

ABSTRACT

The purpose of this study was to determine whether a catecholamine infusion administered to simulate a stress state could alter the pharmacokinetics of administered cocaine and effect the formation of benzoylecgonine, its major metabolite, in the rat. In a previous investigation we determined that catecholamine infusion enhanced the toxicity of continuous cocaine infusion by reducing the time before the onset of convulsions and respiratory arrest. We postulated that this enhanced toxicity was an effect of catecholamines on the pharmacokinetics of cocaine. To test this hypothesis we studied plasma cocaine and benzoylecgonine disposition after intravenous bolus administration of cocaine (5 mg kg(-1)) to 19 male Sprague-Dawley rats and to 10 rats which received an initial loading-dose cocaine infusion of 1 mg kg(-1) min(-1) (for 5 min) followed by continuous infusion of 100 microg kg(-1) min(-1). Rats in both studies randomly received either continuous catecholamine infusion comprising adrenaline (7.25 microg mL(-1)), noradrenaline (4.4 microg mL(-1)) and dopamine (8.0 microg mL(-1)) or saline, administered at a similar rate. Bolus dose cocaine administration, simultaneously with catecholamine infusion, resulted in significantly higher Cmax levels for cocaine (3.8 compared with 2.5 microg mL(-1)) and lower distribution half-lives (3.3 compared with 5.9 min) and central compartment volumes of distribution (1.5 compared with 2.1 L kg(-1)) compared with saline infusion. Benzoylecgonine formation was significantly reduced in rats receiving catecholamines whereas the elimination half-lives (26.3 compared with 25.0 min) and systemic clearances (146 compared with 146 mL kg(-1) min(-1)) were not different. Continuous cocaine infusion (after an initial loading infusion) resulted in the doubling of plasma cocaine levels in rats receiving catecholamines compared with the control group. These data indicate that elevated plasma catecholamines have significant effects on cocaine pharmacokinetics. This might serve to explain the enhanced toxicity from concomitant cocaine and catecholamine infusion demonstrated in previous experiments.


Subject(s)
Catecholamines/pharmacology , Cocaine/analogs & derivatives , Cocaine/pharmacokinetics , Animals , Catecholamines/blood , Cocaine/administration & dosage , Cocaine/biosynthesis , Male , Rats , Rats, Sprague-Dawley
16.
Proc Natl Acad Sci U S A ; 95(17): 10176-81, 1998 Aug 18.
Article in English | MEDLINE | ID: mdl-9707620

ABSTRACT

Cocaine addiction and overdose have long defied specific treatment. To provide a new approach, the high-activity catalytic antibody mAb 15A10 was elicited using a transition-state analog for the hydrolysis of cocaine to nontoxic, nonaddictive products. In a model of cocaine overdose, mAb 15A10 protected rats from cocaine-induced seizures and sudden death in a dose-dependent fashion; a noncatalytic anticocaine antibody did not reduce toxicity. Consistent with accelerated catalysis, the hydrolysis product ecgonine methyl ester was increased >10-fold in plasma of rats receiving mAb 15A10 and lethal amounts of cocaine. In a model of cocaine addiction, mAb 15A10 blocked completely the reinforcing effect of cocaine in rats. mAb 15A10 blocked cocaine specifically and did not affect behavior maintained by milk or by the dopamine reuptake inhibitor bupropion. This artificial cocaine esterase is a rationally designed cocaine antagonist and a catalytic antibody with potential for medicinal use.


Subject(s)
Antibodies, Catalytic/pharmacology , Cocaine/antagonists & inhibitors , Cocaine/toxicity , Substance-Related Disorders/prevention & control , Animals , Antibodies, Monoclonal/pharmacology , Cocaine/metabolism , Disease Models, Animal , Hydrolysis , Male , Rats , Rats, Sprague-Dawley , Reinforcement, Psychology , Self Administration
17.
Biochim Biophys Acta ; 1393(1): 41-8, 1998 Jul 31.
Article in English | MEDLINE | ID: mdl-9714726

ABSTRACT

The present study investigates the effects of various glutathione (GSH) depleting agents on sn-glycerol-3-phosphate acyltransferase (GPAT) activity, the first committed step in adipose triacylglycerol formation. GPAT activity was measured in the presence of [14C]glycerol-3-phosphate and palmitoyl-CoA, using different subcellular fractions. Glutathione deficiency in animals was induced in the presence of diethylmaleate (DEM) or buthionine sulfoximine. In this respect, DEM (1.75 mmoles/kg) was more effective and caused over 75% decrease in GPAT activity within 4 h of DEM administration. Further studies indicated that this decrease in GPAT activity was mainly related to the microsomal form of GPAT, without any significant effect on mitochondrial GPAT activity. Adipocytes incubated with 2.5 mm DEM for 1 h at 37 degrees C also showed a reduction in the adipocyte glutathione content, which was accompanied by decreases in GPAT activity. The effect of DEM on adipocyte GPAT activity was partially reversible in the presence of cell permeable glutathione ethyl ester. Preincubation of adipose tissue homogenates with 2.5 mM DEM at 30 degrees C for 45 min also showed a significant loss of the GPAT activity. The presence of 5 mM dithiothreitol in the preincubation mixture offered a significant protection of the GPAT activity against DEM. However, glutathione was ineffective in this respect as it interfered with the utilization of palmitoyl-CoA in the GPAT assay. Therefore, on the basis of these three different approaches, the present studies suggest that the thiol environment offered by glutathione (in vivo and in vitro studies) or dithiothreitol (in a cell-free system) is critical for the maintenance of GPAT activity.


Subject(s)
Adipocytes/enzymology , Glutathione/deficiency , Glycerol-3-Phosphate O-Acyltransferase/metabolism , Animals , Buthionine Sulfoximine , Glycerol-3-Phosphate O-Acyltransferase/antagonists & inhibitors , Male , Maleates , Microsomes/enzymology , Mitochondria/enzymology , Rats , Rats, Sprague-Dawley
18.
Int J Biochem Cell Biol ; 29(4): 623-34, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9363640

ABSTRACT

Previous studies from this laboratory [Jamdar S. C. and Cao W. F. (1994) Biochem. J. 301, 793-799] show that the adipocyte Mg(2+)-dependent phosphatidate phosphohydrolase (MGPPH), a major regulatory enzyme in adipose triacylglycerol metabolism, requires an active thiol group for its activity and perturbation of this group results in the loss of enzyme activity. Since glutathione (GSH) is important in maintaining the intracellular thiol state, we have used GSH-deficient animals and adipocytes to test the possibility that intracellular GSH concentration is critical in controlling the MGPPH activity. The MGPPH was measured in the presence of aqueous dispersed phosphatidate, and the release of P1 was taken as a measure of enzyme activity. The GSH deficiency in animals and isolated adipocytes was produced in the presence of diethylmaleate (DEM) or buthionine sulfoximine (BSO). Intraperitoneal administration of BSO into animals (3 mmoles/kg) showed 10-25% reduction in the blood and adipose GSH and 25% decline in the adipose MGPPH activity. However, DEM (0.3 ml/kg) was more effective and caused over 70% reduction of the blood and adipose tissue GSH content and 75% decline in the adipose MGPPH activity within 4 hr of drug administration. After 24 hr, these values returned to normal. Adipocytes incubated with 2.5 mM DEM for 60 min at 37 degrees C also showed a significant reduction in the GSH content and the MGPPH activity present in the cytosol and membrane fractions. The loss of membrane MGPPH was associated with decreased rates of triacylglycerol formation from [14C]palmitate. Pre-incubation of adipocyte homogenates with 1 mM DEM also resulted in > 90% decline in the MGPPH activity, which was preventable in the presence of GSH and dithiothreitol. Therefore, these studies suggest that the sulfhydryl environment offered by glutathione is critical for the maintenance of adipocyte MGPPH activity.


Subject(s)
Adipocytes/metabolism , Glutathione/deficiency , Phosphatidate Phosphatase/metabolism , Animals , Buthionine Sulfoximine/pharmacology , Maleates/pharmacology , Rats
19.
Anesthesiology ; 85(3): 497-501, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8853079

ABSTRACT

BACKGROUND: Some patients who undergo cerebral aneurysm surgery require cardiopulmonary bypass and deep hypothermic circulatory arrest. During bypass, these patients often are given large doses of a supplemental anesthetic agent in the hope that additional cerebral protection will be provided. Pharmacologic brain protection, however, has been associated with undesirable side effects. These side effects were evaluated in patients who received large doses of propofol. METHODS: Thirteen neurosurgical patients underwent cardiopulmonary bypass and deep hypothermic circulatory arrest to facilitate clip application to a giant or otherwise high-risk cerebral aneurysm. Electroencephalographic burst suppression was established before bypass with an infusion of propofol, and the infusion was continued until the end of surgery. Hemodynamic and echocardiographic measurements were made before and during the prebypass propofol infusion and again after bypass. Emergence time also was determined. RESULTS: Prebypass propofol at 243 +/- 57 micrograms.kg-1.min-1 decreased vascular resistance from 34 +/- 8 to 27 +/- 8 units without changing heart rate, arterial or filling pressures, cardiac index, stroke volume, or ejection fraction. Propofol blood concentration was 8 +/- 2 micrograms/ml. Myocardial wall motion appeared hyperdynamic at the end of cardiopulmonary bypass, and all patients were weaned therefrom without inotropic support. After bypass, vascular resistance decreased further, and cardiovascular performance was improved compared to baseline values. Nine of the 13 patients emerged from anesthesia and were able to follow commands at 3.1 +/- 1.4 h. Three others had strokes and a fourth had cerebral swelling. CONCLUSIONS: Propofol infused at a rate sufficient to suppress the electroencephalogram does not depress the heart or excessively prolong emergence from anesthesia after cardiopulmonary bypass and deep hypothermic circulatory arrest.


Subject(s)
Anesthetics, Intravenous/pharmacology , Electroencephalography/drug effects , Heart Arrest, Induced , Propofol/pharmacology , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged
20.
J Chromatogr B Biomed Appl ; 681(2): 263-9, 1996 Jun 07.
Article in English | MEDLINE | ID: mdl-8811435

ABSTRACT

An isocratic high-performance liquid chromatographic method with ultraviolet detection at 235 nm is described for the determination of cocaine and its metabolites benzoylecgonine, norcocaine and ecgonine methyl ester in rat plasma, collected during toxicity studies. Following simultaneous solid-phase extraction of all analytes and the internal standard tropacocaine, cocaine, benzoylecgonine and norcocaine were separated on a C18 column. Ecgonine methyl ester and cocaine were separated on coupled cyanopropyl and silica columns, following derivatization of ecgonine methyl ester to p-fluorococaine. The extraction efficiencies of these compounds from plasma ranged from 78 to 87%, while the limits of detection ranged from 35 to 90 ng/ml. The assay was linear from 300 to 5000 ng/ml, and the within-day precision 2 to 8% over this concentration range.


Subject(s)
Chromatography, High Pressure Liquid/methods , Cocaine/analogs & derivatives , Cocaine/blood , Animals , Chromatography, High Pressure Liquid/statistics & numerical data , Gas Chromatography-Mass Spectrometry , Male , Rats , Rats, Sprague-Dawley , Regression Analysis
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