An investigation of chlorbutol in ophthalmic and parenteral solutions
- Authors: Summers, Robert Stanley
- Date: 1967
- Subjects: Parenteral solutions , Solutions (Pharmacy) , Ocular pharmacology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3842 , http://hdl.handle.net/10962/d1007694 , Parenteral solutions , Solutions (Pharmacy) , Ocular pharmacology
- Description: From Introduction Chlorbutol , which is tri-chlor-tertiary-butanol, was first prepared by Willgerodt in 1886 (1). The reaction he used for its preparation is still used today, though slightly modified (2)(3)(4), and is suggested by its original name "acetone-chloroform". The substance was prepared by adding solid potassium hydroxide to a cold mixture of acetone and chloroform (5 ). Chlorbutol is a derivative of the trichlorinated derivative of methane, and its formation may best be described by the use of structural formulae.
- Full Text:
- Date Issued: 1967
- Authors: Summers, Robert Stanley
- Date: 1967
- Subjects: Parenteral solutions , Solutions (Pharmacy) , Ocular pharmacology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3842 , http://hdl.handle.net/10962/d1007694 , Parenteral solutions , Solutions (Pharmacy) , Ocular pharmacology
- Description: From Introduction Chlorbutol , which is tri-chlor-tertiary-butanol, was first prepared by Willgerodt in 1886 (1). The reaction he used for its preparation is still used today, though slightly modified (2)(3)(4), and is suggested by its original name "acetone-chloroform". The substance was prepared by adding solid potassium hydroxide to a cold mixture of acetone and chloroform (5 ). Chlorbutol is a derivative of the trichlorinated derivative of methane, and its formation may best be described by the use of structural formulae.
- Full Text:
- Date Issued: 1967
An investigation into chemical and biological assays of new compounds from aloes
- Authors: Mapp, R K
- Date: 1969
- Subjects: Medicinal plants -- Research -- South Africa , Botanical chemistry , Aloe -- Analysis , Aloe -- Research -- South Africa , Aloe , Aloin
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3850 , http://hdl.handle.net/10962/d1012830
- Description: The drug aloes has been known since earliest times and is mentioned in the Ebers papyrus of circa 1,500 B.C. Alexander the Great is reported to have sent a commission to Socotra to investigate the aloes grown there. The chemical composition of aloes is complex, and being of plant origin, subject to variation. Both the complexity of the chemical constituents and their biological variation has resulted in a very large volume of conflicting material being published on this drug export. Since aloes is used as a purgative for both human and veterinary use, it is obviously important that the dosage and consequently the active constituents, should comply to an accurate means of standardisation. To date, despite extensive world wide research into this drug such standardisation has not been achieved. Even the methods used for the assay of the principal constituent, aloin, vary considerably in their results, and to complicate matters new chemical principles have been isolated from aloes in recent years. Consequently the purpose of this work has been to investigate the main chemical assay methods currently in use, and to determine which was the most accurate, and why discrepancies occurred in the selected assay methods. furthermore the results obtained by chemical assay have been compared with those obtained by biological assay in an attempt to correlate aloin content with purgative activity. Newly isolated compounds have been investigated biologically for the first time, and the biological assays of the resinous, glycosidal and other compounds of aloes have been performed. Intro. p.1-2.
- Full Text:
- Date Issued: 1969
- Authors: Mapp, R K
- Date: 1969
- Subjects: Medicinal plants -- Research -- South Africa , Botanical chemistry , Aloe -- Analysis , Aloe -- Research -- South Africa , Aloe , Aloin
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3850 , http://hdl.handle.net/10962/d1012830
- Description: The drug aloes has been known since earliest times and is mentioned in the Ebers papyrus of circa 1,500 B.C. Alexander the Great is reported to have sent a commission to Socotra to investigate the aloes grown there. The chemical composition of aloes is complex, and being of plant origin, subject to variation. Both the complexity of the chemical constituents and their biological variation has resulted in a very large volume of conflicting material being published on this drug export. Since aloes is used as a purgative for both human and veterinary use, it is obviously important that the dosage and consequently the active constituents, should comply to an accurate means of standardisation. To date, despite extensive world wide research into this drug such standardisation has not been achieved. Even the methods used for the assay of the principal constituent, aloin, vary considerably in their results, and to complicate matters new chemical principles have been isolated from aloes in recent years. Consequently the purpose of this work has been to investigate the main chemical assay methods currently in use, and to determine which was the most accurate, and why discrepancies occurred in the selected assay methods. furthermore the results obtained by chemical assay have been compared with those obtained by biological assay in an attempt to correlate aloin content with purgative activity. Newly isolated compounds have been investigated biologically for the first time, and the biological assays of the resinous, glycosidal and other compounds of aloes have been performed. Intro. p.1-2.
- Full Text:
- Date Issued: 1969
A gas chromatographic study of oils from some Agathosma species (family Rutaceae)
- Persicaner, Peter Henry Robert
- Authors: Persicaner, Peter Henry Robert
- Date: 1972 , 2013-11-13
- Subjects: Rutaceae , Rutaceae -- Therapeutic use , Gas chromatography
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3837 , http://hdl.handle.net/10962/d1007634 , Rutaceae , Rutaceae -- Therapeutic use , Gas chromatography
- Description: From Introduction: Buchu leaf is a very widely used household medicine in South Africa, and is usually administered in the form of a brandy tincture or a vinegar, known as "buchu brandy" and "buchu vinegar" respectively. These preparations have a great reputation in curing diseases of the kidney and urinary tract, and in addition are employed as local applications to bruises, and for the relief of rheumatic pains. We owe its introduction into medicine to the Hottentot, who gave the name "buchu" or "bookoo" to any aromatic herb or shrub which they found suitable for use as a dusting powder.
- Full Text:
- Date Issued: 1972
- Authors: Persicaner, Peter Henry Robert
- Date: 1972 , 2013-11-13
- Subjects: Rutaceae , Rutaceae -- Therapeutic use , Gas chromatography
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3837 , http://hdl.handle.net/10962/d1007634 , Rutaceae , Rutaceae -- Therapeutic use , Gas chromatography
- Description: From Introduction: Buchu leaf is a very widely used household medicine in South Africa, and is usually administered in the form of a brandy tincture or a vinegar, known as "buchu brandy" and "buchu vinegar" respectively. These preparations have a great reputation in curing diseases of the kidney and urinary tract, and in addition are employed as local applications to bruises, and for the relief of rheumatic pains. We owe its introduction into medicine to the Hottentot, who gave the name "buchu" or "bookoo" to any aromatic herb or shrub which they found suitable for use as a dusting powder.
- Full Text:
- Date Issued: 1972
A study of the rabbit eye test system to determine the activity of acidic non-steroidal anti-inflammatory agents
- Authors: Wiseman, Ian Charles
- Date: 1977
- Subjects: Nonsteroidal anti-inflammatory agents , Anti-inflammatory agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3855 , http://hdl.handle.net/10962/d1013276
- Description: From introduction : "Inflammation per se, has been defined sufficiently to permit a rational approach to the search for drugs that modify this process, but satisfactory animal models for most rheumatoid diseases are not available". (Swingle 1974) In the search for new meaningful procedures for the detection and evaluation of anti-inflammatory drugs, the rabbit eye as a test system was studied.
- Full Text:
- Date Issued: 1977
- Authors: Wiseman, Ian Charles
- Date: 1977
- Subjects: Nonsteroidal anti-inflammatory agents , Anti-inflammatory agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3855 , http://hdl.handle.net/10962/d1013276
- Description: From introduction : "Inflammation per se, has been defined sufficiently to permit a rational approach to the search for drugs that modify this process, but satisfactory animal models for most rheumatoid diseases are not available". (Swingle 1974) In the search for new meaningful procedures for the detection and evaluation of anti-inflammatory drugs, the rabbit eye as a test system was studied.
- Full Text:
- Date Issued: 1977
The in vivo and quantitative assessment of topical corticosteroid formulations
- Authors: Coleman, Gerald Leslie
- Date: 1978 , 2013-10-14
- Subjects: Dermatopharmacology , Dermatologic agents , Skin absorption , Adrenocortical hormones -- Therapeutic use , Transdermal medication -- Evaluation
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3857 , http://hdl.handle.net/10962/d1013337
- Full Text:
- Date Issued: 1978
- Authors: Coleman, Gerald Leslie
- Date: 1978 , 2013-10-14
- Subjects: Dermatopharmacology , Dermatologic agents , Skin absorption , Adrenocortical hormones -- Therapeutic use , Transdermal medication -- Evaluation
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3857 , http://hdl.handle.net/10962/d1013337
- Full Text:
- Date Issued: 1978
The study of the metabolism of phenylbutazone (4-butyl-1,2 -diphenylpyrazolidine - 3,5 - dione) in rats
- Authors: Alexander, Dorothy Mary
- Date: 1978 , 2013-10-18
- Subjects: Drugs -- Metabolism , Phenylbutazone
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3832 , http://hdl.handle.net/10962/d1007468 , Drugs -- Metabolism , Phenylbutazone
- Description: In this study the metabolism of the anti-arthritic drug, phenylbutazone, was investigated in female Wistar rats, and the results compared with those of other workers in this field. Two interrelated projects were undertaken. The first covered the pattern of excretion, isolation and characterisation of the metabolites and decomposition products of phenylbutazone in rats dosed post-orally with the drug. It was found that the major route of excretion was via the urine and over 50% of the administered dose was excreted in the first 24 hours by this route. A small percentage of the dose was excreted in the faeces. The following compounds were identified using chromatographic and autoradiographic techniques: p-Hydroxy derivative of phenylbutazone γ-Hydroxy derivative of phenylbutazone in both its molecular forms (ring lactone and straight chain hydroxyl) 4-Hydroxy derivative of phenylbutazone p-γ-Dihydroxy derivative of phenylbutazone p-4-Dihydroxy derivative of phenylbutazone Hydrolysable conjugates (possibly glucuronides) Water soluble non-hydrolysable conjugates. The second project dealt with the quantitation of the water insoluble compounds isolated in the initial work. Using a unique technique, combining inverse isotope dilution assay and spectrophotometric analysis, it was found that the major metabolite was the γ-hydroxy derivative of phenylbutazone, present in both its molecular forms. Oxyphenbutazone was a minor metabolite and the p-γ-dihydroxy derivative of phenylbutazone was present only in very low concentration. These results did not conform with those of previous workers in this field who reported the γ-hydroxy derivative of phenylbutazone, in one molecular form only, as the major metabolite and the dihydroxy derivative as the second metabolite with a higher concentration in the urine than oxyphenbutazone. This disparity could be due to the fact that these workers took no account of the presence of the two molecular forms of the γ-hydroxy derivative of phenylbutazone with their different polarities and different Rf values. The present study showed that the straight chain hydroxyl isomer was probably mistakenly identified as the p-γ-dihydroxy derivative of phenylbutazone. This theory is supported by the fact that the percentage dose recovered by the previous workers of the γ-hydroxy and p-γ-dihydroxy derivatives together equalled the percentage dose recovered in this study of the two molecular forms of the γ-hydroxy derivative. , KMBT_363 , Adobe Acrobat 9.54 Paper Capture Plug-in
- Full Text:
- Date Issued: 1978
- Authors: Alexander, Dorothy Mary
- Date: 1978 , 2013-10-18
- Subjects: Drugs -- Metabolism , Phenylbutazone
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3832 , http://hdl.handle.net/10962/d1007468 , Drugs -- Metabolism , Phenylbutazone
- Description: In this study the metabolism of the anti-arthritic drug, phenylbutazone, was investigated in female Wistar rats, and the results compared with those of other workers in this field. Two interrelated projects were undertaken. The first covered the pattern of excretion, isolation and characterisation of the metabolites and decomposition products of phenylbutazone in rats dosed post-orally with the drug. It was found that the major route of excretion was via the urine and over 50% of the administered dose was excreted in the first 24 hours by this route. A small percentage of the dose was excreted in the faeces. The following compounds were identified using chromatographic and autoradiographic techniques: p-Hydroxy derivative of phenylbutazone γ-Hydroxy derivative of phenylbutazone in both its molecular forms (ring lactone and straight chain hydroxyl) 4-Hydroxy derivative of phenylbutazone p-γ-Dihydroxy derivative of phenylbutazone p-4-Dihydroxy derivative of phenylbutazone Hydrolysable conjugates (possibly glucuronides) Water soluble non-hydrolysable conjugates. The second project dealt with the quantitation of the water insoluble compounds isolated in the initial work. Using a unique technique, combining inverse isotope dilution assay and spectrophotometric analysis, it was found that the major metabolite was the γ-hydroxy derivative of phenylbutazone, present in both its molecular forms. Oxyphenbutazone was a minor metabolite and the p-γ-dihydroxy derivative of phenylbutazone was present only in very low concentration. These results did not conform with those of previous workers in this field who reported the γ-hydroxy derivative of phenylbutazone, in one molecular form only, as the major metabolite and the dihydroxy derivative as the second metabolite with a higher concentration in the urine than oxyphenbutazone. This disparity could be due to the fact that these workers took no account of the presence of the two molecular forms of the γ-hydroxy derivative of phenylbutazone with their different polarities and different Rf values. The present study showed that the straight chain hydroxyl isomer was probably mistakenly identified as the p-γ-dihydroxy derivative of phenylbutazone. This theory is supported by the fact that the percentage dose recovered by the previous workers of the γ-hydroxy and p-γ-dihydroxy derivatives together equalled the percentage dose recovered in this study of the two molecular forms of the γ-hydroxy derivative. , KMBT_363 , Adobe Acrobat 9.54 Paper Capture Plug-in
- Full Text:
- Date Issued: 1978
Adreno-active substances and the pineal gland
- Authors: Midlane, Graham Wallace
- Date: 1979
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3738 , http://hdl.handle.net/10962/d1001530
- Description: The pineal gland, a biochemically very active neuroendocrine transducer which is innervated by the sympathetic nervous system, was used in vivo to evaluate the effect of different þ-adrenoceptor agonists and antagonists on pineal enzyme levels. Hydroxyindole-O-methyltransferase (HIOMT), an enzyme with a circadian activity and unknown control was not significantly affected by these drugs. The activity of serotonin N-acetyltransferase, another pineal enzyme with a greater amplitude of circadian rhythmicity and which is under noradrenergic neural control, the degree of blockade depending on the selectivity and affinity of the agent used. An attempt was also made to alter the oestrous cycle of the rat by dosing with þ-active substances. Only propranolol had any effect on the oestrous cycle. It was not possible to establish an absolute link between the alteration in pineal enzyme activity and an influence on the oestrous cycle. It was concluded that the pineal enzyme studies are useful pharmacological means for evaluating þ-active substances
- Full Text:
- Date Issued: 1979
- Authors: Midlane, Graham Wallace
- Date: 1979
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3738 , http://hdl.handle.net/10962/d1001530
- Description: The pineal gland, a biochemically very active neuroendocrine transducer which is innervated by the sympathetic nervous system, was used in vivo to evaluate the effect of different þ-adrenoceptor agonists and antagonists on pineal enzyme levels. Hydroxyindole-O-methyltransferase (HIOMT), an enzyme with a circadian activity and unknown control was not significantly affected by these drugs. The activity of serotonin N-acetyltransferase, another pineal enzyme with a greater amplitude of circadian rhythmicity and which is under noradrenergic neural control, the degree of blockade depending on the selectivity and affinity of the agent used. An attempt was also made to alter the oestrous cycle of the rat by dosing with þ-active substances. Only propranolol had any effect on the oestrous cycle. It was not possible to establish an absolute link between the alteration in pineal enzyme activity and an influence on the oestrous cycle. It was concluded that the pineal enzyme studies are useful pharmacological means for evaluating þ-active substances
- Full Text:
- Date Issued: 1979
Aspects of the bioavailability of topical corticosteroid formulations
- Authors: Magnus, Ashley Denis
- Date: 1979
- Subjects: Adrenocortical hormones , Dermatopharmacology , Dermatologic agents , Transdermal medication
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3724 , http://hdl.handle.net/10962/d1001458
- Description: Two possible variables of the McKenzie/Stoughton blanching assay, namely amount applied to the test site and occlusion time have been investigated. Subsequently, two topical steroid preparations, Synalar cream (0,025% fluocinolone acetonide) and Betnovate cream (0,1% betamethasone 17- valerate) were extemporaneously diluted with five and six placebo bases respectively. Taking cognizance of the two possible variables, these diluted preparations were assessed in vivo using a modified version of the McKenzie/Stoughton blanching assay for blanching activity over a 14 month period. It was found that the base E45, which is slightly alkali, had the greatest effect on both preparations. In the case of betamethasone 17-valerate this base caused the conversion to the less active isomer, betamethasone 21-valerate whereas at the end of the 14 month test period it was found that the Synalar/E45 dilution contained no fluocinolone acetonide. Quantitative analysis of all the diluted preparations by high performance liquid chromatography using a reverse-phase system was performed. The data obtained from the systematic studies of the effects of varying concentrations and occlusion times were presented at the Eleventh National Congress of the South African Pharmacological Society
- Full Text:
- Date Issued: 1979
- Authors: Magnus, Ashley Denis
- Date: 1979
- Subjects: Adrenocortical hormones , Dermatopharmacology , Dermatologic agents , Transdermal medication
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3724 , http://hdl.handle.net/10962/d1001458
- Description: Two possible variables of the McKenzie/Stoughton blanching assay, namely amount applied to the test site and occlusion time have been investigated. Subsequently, two topical steroid preparations, Synalar cream (0,025% fluocinolone acetonide) and Betnovate cream (0,1% betamethasone 17- valerate) were extemporaneously diluted with five and six placebo bases respectively. Taking cognizance of the two possible variables, these diluted preparations were assessed in vivo using a modified version of the McKenzie/Stoughton blanching assay for blanching activity over a 14 month period. It was found that the base E45, which is slightly alkali, had the greatest effect on both preparations. In the case of betamethasone 17-valerate this base caused the conversion to the less active isomer, betamethasone 21-valerate whereas at the end of the 14 month test period it was found that the Synalar/E45 dilution contained no fluocinolone acetonide. Quantitative analysis of all the diluted preparations by high performance liquid chromatography using a reverse-phase system was performed. The data obtained from the systematic studies of the effects of varying concentrations and occlusion times were presented at the Eleventh National Congress of the South African Pharmacological Society
- Full Text:
- Date Issued: 1979
The evaluation of melatonin as a possible antidepressive
- Authors: Skene, Debra Jean
- Date: 1980
- Subjects: Melatonin , Antidepressants
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3728 , http://hdl.handle.net/10962/d1001465
- Description: Melatonin, a hormone of the pineal gland, was evaluated in a variety of animal models of depression. Measurements of the frog righting reflex and rat locomotor activity showed that low doses of melatonin have a serotonin-like potentiating effect following monoamine oxidase inhibition. High doses of melatonin caused a reduction in the duration of rat immobility in the Porsolt model of depression and exerted a chlorpromazine-like effect on conditioned avoidance behaviour. In view of the indoleamine hypothesis of depressive disorders, the possibility of melatonin being a potential antidepressive is discussed and it is concluded that melatonin might be useful in the treatment of "agitated" depressions
- Full Text:
- Date Issued: 1980
- Authors: Skene, Debra Jean
- Date: 1980
- Subjects: Melatonin , Antidepressants
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3728 , http://hdl.handle.net/10962/d1001465
- Description: Melatonin, a hormone of the pineal gland, was evaluated in a variety of animal models of depression. Measurements of the frog righting reflex and rat locomotor activity showed that low doses of melatonin have a serotonin-like potentiating effect following monoamine oxidase inhibition. High doses of melatonin caused a reduction in the duration of rat immobility in the Porsolt model of depression and exerted a chlorpromazine-like effect on conditioned avoidance behaviour. In view of the indoleamine hypothesis of depressive disorders, the possibility of melatonin being a potential antidepressive is discussed and it is concluded that melatonin might be useful in the treatment of "agitated" depressions
- Full Text:
- Date Issued: 1980
A study of the interactions between phenytoin and pharmaceutical antacids, excipients and adsorbents
- Authors: Gilbert, Peter John
- Date: 1981 , 2013-03-14
- Subjects: Phenytoin , Antacids
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3821 , http://hdl.handle.net/10962/d1004935 , Phenytoin , Antacids
- Full Text:
- Date Issued: 1981
A study of the interactions between phenytoin and pharmaceutical antacids, excipients and adsorbents
- Authors: Gilbert, Peter John
- Date: 1981 , 2013-03-14
- Subjects: Phenytoin , Antacids
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3821 , http://hdl.handle.net/10962/d1004935 , Phenytoin , Antacids
- Full Text:
- Date Issued: 1981
The comparative bioavailability and in vitro assessment of solid oral dosage forms of paracetamol
- Authors: Braae, Karen
- Date: 1981 , 2013-04-02
- Subjects: Acetaminophen , Bioavailability , Drugs -- Bioavailability , Drugs -- Dosage forms , Analysis of variance
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3827 , http://hdl.handle.net/10962/d1006288 , Acetaminophen , Bioavailability , Drugs -- Bioavailability , Drugs -- Dosage forms , Analysis of variance
- Description: The dissolution profiles of eight lots of paracetamol tablets representing seven different tablet brands are determined in a USP rotating basket assembly and a stationary basket-rotating paddle apparatus. The in vitro data are expressed in terms of dissolution parameters and inter-tablet differences are assessed statistically using analysis of variance (ANOVA) and the Scheffe test. Highly significant differences are observed between a number of the tablets at the 95% confidence level. Representative tablets from the dissolution rate study and a control dose of paracetamol dissolved in water are subsequently investigated in a 4 x 4 latin square design bioavailability trial. Serum and urine samples are collected and assayed for paracetamol alone (serum) and together with its metabolites (urine) by means of high pressure liquid chromatography. The in vivo data are expressed in terms of bioavailability parameters and differences between the test doses are assessed by means of ANOVA. No significant differences are observed between the dosage forms at the 95% confidence level.
- Full Text:
- Date Issued: 1981
- Authors: Braae, Karen
- Date: 1981 , 2013-04-02
- Subjects: Acetaminophen , Bioavailability , Drugs -- Bioavailability , Drugs -- Dosage forms , Analysis of variance
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3827 , http://hdl.handle.net/10962/d1006288 , Acetaminophen , Bioavailability , Drugs -- Bioavailability , Drugs -- Dosage forms , Analysis of variance
- Description: The dissolution profiles of eight lots of paracetamol tablets representing seven different tablet brands are determined in a USP rotating basket assembly and a stationary basket-rotating paddle apparatus. The in vitro data are expressed in terms of dissolution parameters and inter-tablet differences are assessed statistically using analysis of variance (ANOVA) and the Scheffe test. Highly significant differences are observed between a number of the tablets at the 95% confidence level. Representative tablets from the dissolution rate study and a control dose of paracetamol dissolved in water are subsequently investigated in a 4 x 4 latin square design bioavailability trial. Serum and urine samples are collected and assayed for paracetamol alone (serum) and together with its metabolites (urine) by means of high pressure liquid chromatography. The in vivo data are expressed in terms of bioavailability parameters and differences between the test doses are assessed by means of ANOVA. No significant differences are observed between the dosage forms at the 95% confidence level.
- Full Text:
- Date Issued: 1981
The study of the potentiation of anticholinergic side effects of tricyclic antidepressives by female sex steroids
- Authors: Kok, Eric Charl
- Date: 1981
- Subjects: Antidepressants , Steroid hormones
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3822 , http://hdl.handle.net/10962/d1005623 , Antidepressants , Steroid hormones
- Description: It has been recorded that women respond to tricyclic antidepressives with a greater incidence of anticholinergic side effects than men do, particularly women taking an exogenous source of oestrogen. The aim of this study was to investigate the influence that ethinyl oestradiol and Premarin© had on the metabolism of a number of tricyclic antidepressives, and also the influence they had on the binding ability of microsomes to imipramine. Rat hepatocyctes and microsomes were used. Detection techniques used were High Pressure Liquid Chromatography and Spectrophotometry respectively. In addition to these studies, a study of the anticholinergic activity of Nomifensine, tricyclic antidepressives and their derivatives was performed on a rat jujenum. Results conclusively showed that ethinyl oestradiol had a marked influence on the metabolism of the tricyclic antidepressives studied. Premarin© had Iittle, if any influence. However, both ethinyl oestradiol and Premarin© affected the binding of microsomes to imipramine, but ethinyl oestradiol had the greater effect. The parent compound in each case exhibited a higher pAZ value. Results indicate that a possible explanation for the increased anticholinergic side effect is due to an inhibition of the metabolism of the tricyclic antidepressives by oestrogen.
- Full Text:
- Date Issued: 1981
- Authors: Kok, Eric Charl
- Date: 1981
- Subjects: Antidepressants , Steroid hormones
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3822 , http://hdl.handle.net/10962/d1005623 , Antidepressants , Steroid hormones
- Description: It has been recorded that women respond to tricyclic antidepressives with a greater incidence of anticholinergic side effects than men do, particularly women taking an exogenous source of oestrogen. The aim of this study was to investigate the influence that ethinyl oestradiol and Premarin© had on the metabolism of a number of tricyclic antidepressives, and also the influence they had on the binding ability of microsomes to imipramine. Rat hepatocyctes and microsomes were used. Detection techniques used were High Pressure Liquid Chromatography and Spectrophotometry respectively. In addition to these studies, a study of the anticholinergic activity of Nomifensine, tricyclic antidepressives and their derivatives was performed on a rat jujenum. Results conclusively showed that ethinyl oestradiol had a marked influence on the metabolism of the tricyclic antidepressives studied. Premarin© had Iittle, if any influence. However, both ethinyl oestradiol and Premarin© affected the binding of microsomes to imipramine, but ethinyl oestradiol had the greater effect. The parent compound in each case exhibited a higher pAZ value. Results indicate that a possible explanation for the increased anticholinergic side effect is due to an inhibition of the metabolism of the tricyclic antidepressives by oestrogen.
- Full Text:
- Date Issued: 1981
Reaction of carbohydrates with the sulphuryl chloride-N, N-dimethyl formamide reagent
- Authors: Mabusela, Wilfred Thozamile
- Date: 1982
- Subjects: Chemical reactions Carbohydrates
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3731 , http://hdl.handle.net/10962/d1001470
- Description: An investigation of the reaction of the sulphuryl chloride-N, N-dimethyl formamide reagent with several carbohydrate compounds, containing free hydroxyl groups, was undertaken, mainly with the view of looking at substitution of the hydroxyl groups with chlorine atoms. The reaction was found to lead to substitution of both primary and secondary hydroxyl groups with chlorine, with inversion of configuration in the latter case. The reagent was further found to effect formylation and chlorosulphation of secondary hydroxyl groups, where nucleophilic substitution by a chlorine was not favourable. Studies involving the methyl pentopyranosides, showed that the reagent was particularly useful in the chlorosulphation and chlorination of sugars, compared with the hexopyranosides.
- Full Text:
- Date Issued: 1982
- Authors: Mabusela, Wilfred Thozamile
- Date: 1982
- Subjects: Chemical reactions Carbohydrates
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3731 , http://hdl.handle.net/10962/d1001470
- Description: An investigation of the reaction of the sulphuryl chloride-N, N-dimethyl formamide reagent with several carbohydrate compounds, containing free hydroxyl groups, was undertaken, mainly with the view of looking at substitution of the hydroxyl groups with chlorine atoms. The reaction was found to lead to substitution of both primary and secondary hydroxyl groups with chlorine, with inversion of configuration in the latter case. The reagent was further found to effect formylation and chlorosulphation of secondary hydroxyl groups, where nucleophilic substitution by a chlorine was not favourable. Studies involving the methyl pentopyranosides, showed that the reagent was particularly useful in the chlorosulphation and chlorination of sugars, compared with the hexopyranosides.
- Full Text:
- Date Issued: 1982
The effect of tricyclic antidepressant drugs on the uptake and metabolism of serotonin by the pineal gland in organ culture
- Authors: Pillay, Manoranjenni
- Date: 1983 , 2013-04-05
- Subjects: Antidepressants , Pineal gland -- Metabolsim , Serotonin
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3828 , http://hdl.handle.net/10962/d1007053 , Antidepressants , Pineal gland -- Metabolsim , Serotonin
- Description: The effect of tricyclic antidepressants (TADs) on a variety of pineal functions was assessed. TADs affected the uptake of ³H-5HT into bovine pineal slices within a particular concentration range of these drugs, DESI, CLOMI and IMI appeared to inhibit uptake slightly, within a limited concentration range. Surprisingly, DESI appeared to be a relatively potent 5HT uptake inhibitor. The 5-HT re-uptake system in the pineal probably differes from that in brain tissue. TADs had a marked effect on the metabolism of ³H-5HT in the rat pineal, in an organ culture system, MEL and N-acetylserotonin synthesis increased for the first 11 days and thereafter a slight decrease was observed. HTOH and HIAA also showed an initial increase followed by a slight decrease in synthesis. The synthesis of MTOH and MIAA was decreased. The possibility that TADs could affect HIOMT and SNAT synthesis and thereby change the metabolic pattern of 5-HT was investigated. TADs appeared to stimulate SNAT initially and thereafter a slight decrease from peak activity was observed. This is probably due to stimulation followed by development of subsensitivity of β-receptors, HIOMT activity also appeared to be affected by TADs. The existence of two types of HIOMT is suggested. There is a possibility that these changes in the metabolism of 5-HT could be implicated in the mechanism of action of TADs. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1983
- Authors: Pillay, Manoranjenni
- Date: 1983 , 2013-04-05
- Subjects: Antidepressants , Pineal gland -- Metabolsim , Serotonin
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3828 , http://hdl.handle.net/10962/d1007053 , Antidepressants , Pineal gland -- Metabolsim , Serotonin
- Description: The effect of tricyclic antidepressants (TADs) on a variety of pineal functions was assessed. TADs affected the uptake of ³H-5HT into bovine pineal slices within a particular concentration range of these drugs, DESI, CLOMI and IMI appeared to inhibit uptake slightly, within a limited concentration range. Surprisingly, DESI appeared to be a relatively potent 5HT uptake inhibitor. The 5-HT re-uptake system in the pineal probably differes from that in brain tissue. TADs had a marked effect on the metabolism of ³H-5HT in the rat pineal, in an organ culture system, MEL and N-acetylserotonin synthesis increased for the first 11 days and thereafter a slight decrease was observed. HTOH and HIAA also showed an initial increase followed by a slight decrease in synthesis. The synthesis of MTOH and MIAA was decreased. The possibility that TADs could affect HIOMT and SNAT synthesis and thereby change the metabolic pattern of 5-HT was investigated. TADs appeared to stimulate SNAT initially and thereafter a slight decrease from peak activity was observed. This is probably due to stimulation followed by development of subsensitivity of β-receptors, HIOMT activity also appeared to be affected by TADs. The existence of two types of HIOMT is suggested. There is a possibility that these changes in the metabolism of 5-HT could be implicated in the mechanism of action of TADs. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1983
Serotonin binding in vitro by releasable proteins from human blood platelets
- Authors: Heemstra, Valerie Lawrence
- Date: 1984 , 2013-04-10
- Subjects: Serotonin , Serotonin -- Metabolism
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3829 , http://hdl.handle.net/10962/d1007215 , Serotonin , Serotonin -- Metabolism
- Description: Among the substances released from human blood platelets are serotonin and various proteins. It was hypothesized that one of these proteins binds serotonin and that serotonin might be important to the protein's function or that the protein might be important to serotonin's function. Two platelet-specific proteins, platelet factor 4 (PF4) and ß-thromboglobulin ( ßTG) were found to bind serotonin in vitro. Endogenous PF4 was isolated by serotonin-affinity chromatography and was identified by radioimmunoassay. Purified l¹²⁵ I] -PF4 and native PF4 bound to and eluted from a serotonin-affinity column similarly. Ultrafiltration of the homologous protein, (ßTG, with [¹⁴C]-serotonin demonstrated binding of about 8 moles serotonin per mole tetrameric ßTG with a dissociation con stant of about 4 x 10-8ThesisThesis⁻⁸ M. Equilibrium dialysis of PF4 with radiolabelled serotonin was attempted, but no binding constant values were obtained because serotonin apparently bound to the dialysis membrane. Since EDTA was one of the two agents that eluted PF4 from the serotonin-affinity gel, calcium binding by -PF4 was investigated by equilibrium dialysis. Evidence was obtained for positively cooperative binding of calcium ions by PF4. It is concluded that PF4 and ßTG bind serotonin in vitro, that they may also bind in vivo when platelets undergo release, and that the functions of serotonin, PF4 and ßTG may be mediated in part by serotonin-protein associations. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1984
- Authors: Heemstra, Valerie Lawrence
- Date: 1984 , 2013-04-10
- Subjects: Serotonin , Serotonin -- Metabolism
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3829 , http://hdl.handle.net/10962/d1007215 , Serotonin , Serotonin -- Metabolism
- Description: Among the substances released from human blood platelets are serotonin and various proteins. It was hypothesized that one of these proteins binds serotonin and that serotonin might be important to the protein's function or that the protein might be important to serotonin's function. Two platelet-specific proteins, platelet factor 4 (PF4) and ß-thromboglobulin ( ßTG) were found to bind serotonin in vitro. Endogenous PF4 was isolated by serotonin-affinity chromatography and was identified by radioimmunoassay. Purified l¹²⁵ I] -PF4 and native PF4 bound to and eluted from a serotonin-affinity column similarly. Ultrafiltration of the homologous protein, (ßTG, with [¹⁴C]-serotonin demonstrated binding of about 8 moles serotonin per mole tetrameric ßTG with a dissociation con stant of about 4 x 10-8ThesisThesis⁻⁸ M. Equilibrium dialysis of PF4 with radiolabelled serotonin was attempted, but no binding constant values were obtained because serotonin apparently bound to the dialysis membrane. Since EDTA was one of the two agents that eluted PF4 from the serotonin-affinity gel, calcium binding by -PF4 was investigated by equilibrium dialysis. Evidence was obtained for positively cooperative binding of calcium ions by PF4. It is concluded that PF4 and ßTG bind serotonin in vitro, that they may also bind in vivo when platelets undergo release, and that the functions of serotonin, PF4 and ßTG may be mediated in part by serotonin-protein associations. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1984
Topical immunotherapy for Pseudomonas keratitis : use of antilipopolyssacharide plasma
- Authors: Rauch, Andrew Johan
- Date: 1984 , 2013-03-13
- Subjects: Pseudomonas infections , Immunotherapy
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3817 , http://hdl.handle.net/10962/d1004910 , Pseudomonas infections , Immunotherapy
- Description: Pseudomonas aeruginosa is an opportunistic pathogen capable of infecting the human cornea. Such infections are difficult to treat, and are often fulminative, in that the infected eye is lost, or severely scarred. The use of alternative therapeutic agents has been necessitated by the frequent failure of conventional antibiotic therapy. Equine hyperimmune antilipopolysaccharide plasma (Anti-LPS) was obtained by the plasmapheresis of suitably immunized horses. The plasma contained 1,O- 1 ,5g/ml of LPS-precipitible IgG antibodies. Topical administration of Anti-LPS as a lavage was shown to be effective against Pseudomonas keratitis in rabbits and guinea pigs. Subsequent use of topical corticosteroids was found to further reduce corneal pathology. The improvement noted in these experimental infections involved all three parameters measured, area of keratitis, depth of lesion, and degree of vascularization. In vitro , Anti-LPS was shown to be rapidly bactericidal for Gram negative bacteria. The plasma can therefore be said to have a dual mechanism of action: antitoxic, and antibacterial. Ocular administration of Anti-LPS, by both the topical and subconjunctival routes, was well tolerated by both rabbits and baboons. In conclusion, Anti-LPS is a potentially useful immunotherapeutic agent with many applications in both veteriary and human medicine, particularly in the treatment of surface infections involving antibiotic-resistant Gram negative bacteria , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1984
- Authors: Rauch, Andrew Johan
- Date: 1984 , 2013-03-13
- Subjects: Pseudomonas infections , Immunotherapy
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3817 , http://hdl.handle.net/10962/d1004910 , Pseudomonas infections , Immunotherapy
- Description: Pseudomonas aeruginosa is an opportunistic pathogen capable of infecting the human cornea. Such infections are difficult to treat, and are often fulminative, in that the infected eye is lost, or severely scarred. The use of alternative therapeutic agents has been necessitated by the frequent failure of conventional antibiotic therapy. Equine hyperimmune antilipopolysaccharide plasma (Anti-LPS) was obtained by the plasmapheresis of suitably immunized horses. The plasma contained 1,O- 1 ,5g/ml of LPS-precipitible IgG antibodies. Topical administration of Anti-LPS as a lavage was shown to be effective against Pseudomonas keratitis in rabbits and guinea pigs. Subsequent use of topical corticosteroids was found to further reduce corneal pathology. The improvement noted in these experimental infections involved all three parameters measured, area of keratitis, depth of lesion, and degree of vascularization. In vitro , Anti-LPS was shown to be rapidly bactericidal for Gram negative bacteria. The plasma can therefore be said to have a dual mechanism of action: antitoxic, and antibacterial. Ocular administration of Anti-LPS, by both the topical and subconjunctival routes, was well tolerated by both rabbits and baboons. In conclusion, Anti-LPS is a potentially useful immunotherapeutic agent with many applications in both veteriary and human medicine, particularly in the treatment of surface infections involving antibiotic-resistant Gram negative bacteria , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1984
Comparative bioavailability and ranking of topical corticosteroid formulations
- Authors: Meyer, Eric
- Date: 1985
- Subjects: Adrenocortical hormones -- Therapeutic use Drugs -- Bioavailability Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3732 , http://hdl.handle.net/10962/d1001471
- Description: Numerous experiments in recent years have indicated differences in the bioavailability of corticosteroids from seemingly identical topical dosage forms. The human blanching assay was utilized in this study to assess the comparative blanching activities of various locally manufactured proprietary corticosteroid preparations. The first experiment was performed to assess the relative blanching activities of six semi - solid preparations containing the same concentration of betamethasone 17-valerate. The preparations used were Betnovate cream and ointment, Persivate cream and ointment and Celestoderm-V cream and ointment. This was followed, in the second experiment, by the investigation of the blanching activities of two lotions containing betamethasone 17-valerate (Betnovate and Celestoderm-V) and a lotion containing betamethasone 17,21- dipropionate (Diprosone). The third experiment involved a study of six semi-solid proprietary corticosteroid-containing formulations, viz. Dermovate (clobetasol propionate) cream and ointment, Betnovate (betamethasone 17-valerate) cream and ointment and Eumovate (clobetasone butyrate) cream and ointment. This investigation was prompted by claims in advertisements in the medical media that Dermovate is therapeutically more efficacious than Betnovate which is more efficacious than Eumovate. The penultimate experiment in this study served the purpose of finding a corticosteroid-containing preparation that falls into the moderately potent group of corticosteroid formulations, as described in the United Kingdom MIMS. This preparation was used in the final experiment which was undertaken to ascertain the potency category of Florone (diflorasone diacetate) cream and ointment.
- Full Text:
- Date Issued: 1985
- Authors: Meyer, Eric
- Date: 1985
- Subjects: Adrenocortical hormones -- Therapeutic use Drugs -- Bioavailability Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3732 , http://hdl.handle.net/10962/d1001471
- Description: Numerous experiments in recent years have indicated differences in the bioavailability of corticosteroids from seemingly identical topical dosage forms. The human blanching assay was utilized in this study to assess the comparative blanching activities of various locally manufactured proprietary corticosteroid preparations. The first experiment was performed to assess the relative blanching activities of six semi - solid preparations containing the same concentration of betamethasone 17-valerate. The preparations used were Betnovate cream and ointment, Persivate cream and ointment and Celestoderm-V cream and ointment. This was followed, in the second experiment, by the investigation of the blanching activities of two lotions containing betamethasone 17-valerate (Betnovate and Celestoderm-V) and a lotion containing betamethasone 17,21- dipropionate (Diprosone). The third experiment involved a study of six semi-solid proprietary corticosteroid-containing formulations, viz. Dermovate (clobetasol propionate) cream and ointment, Betnovate (betamethasone 17-valerate) cream and ointment and Eumovate (clobetasone butyrate) cream and ointment. This investigation was prompted by claims in advertisements in the medical media that Dermovate is therapeutically more efficacious than Betnovate which is more efficacious than Eumovate. The penultimate experiment in this study served the purpose of finding a corticosteroid-containing preparation that falls into the moderately potent group of corticosteroid formulations, as described in the United Kingdom MIMS. This preparation was used in the final experiment which was undertaken to ascertain the potency category of Florone (diflorasone diacetate) cream and ointment.
- Full Text:
- Date Issued: 1985
High performance liquid chromatographic analysis of erythromycin in serum and urine
- Authors: Stubbs, Christopher
- Date: 1985 , 2013-03-13
- Subjects: High performance liquid chromatography , Erythromycin , Erythromycin -- Pharmacokinetics , Chromatographic analysis
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3813 , http://hdl.handle.net/10962/d1004581 , High performance liquid chromatography , Erythromycin , Erythromycin -- Pharmacokinetics , Chromatographic analysis
- Description: Erythromycin, a macrolide antibiotic used mainly against gram-positive bacteria has been in clinical use since 1952 (1). Previous pharmacokinetic data published on this antibiotic have been derived predominantly from microbiological assay techniques. However, these techniques are relatively imprecise as well as being non-specific and extremely tedious to perform. A novel high performance liquid chromatographic analysis of erythromycin in human serum and urine using U.V. detection at 200 nm and/or electrochemical detection using both an amperometric and a coulometric electrochemical detector is presented. The method involves a solid phase extraction procedure followed by a simple phase separation step and chromatography on a reverse phase column. In order to select the optimum U.V. detector for this analysis, five "state of the art" detectors were compared in terms of their signal-to-noise ratios at U.V. wavelengths between 200 and 210 nm. A known metabolite des-N-methylerythromycin is readily detectable using U.V. detection, whilst another metabolite/degradation product anhydroerythromycin is not seen using U.V. detection but is readily observable using an electrochemical detector. The method has a limit of sensitivity of 0.25 μg/mL and 1.00 μg/mL in serum and urine respectively (U.V. detection) and is sufficiently sensitive to monitor serum and urine concentrations of erythromycin in man after administration of a single 500 mg erythromycin stearate tablet. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1985
- Authors: Stubbs, Christopher
- Date: 1985 , 2013-03-13
- Subjects: High performance liquid chromatography , Erythromycin , Erythromycin -- Pharmacokinetics , Chromatographic analysis
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3813 , http://hdl.handle.net/10962/d1004581 , High performance liquid chromatography , Erythromycin , Erythromycin -- Pharmacokinetics , Chromatographic analysis
- Description: Erythromycin, a macrolide antibiotic used mainly against gram-positive bacteria has been in clinical use since 1952 (1). Previous pharmacokinetic data published on this antibiotic have been derived predominantly from microbiological assay techniques. However, these techniques are relatively imprecise as well as being non-specific and extremely tedious to perform. A novel high performance liquid chromatographic analysis of erythromycin in human serum and urine using U.V. detection at 200 nm and/or electrochemical detection using both an amperometric and a coulometric electrochemical detector is presented. The method involves a solid phase extraction procedure followed by a simple phase separation step and chromatography on a reverse phase column. In order to select the optimum U.V. detector for this analysis, five "state of the art" detectors were compared in terms of their signal-to-noise ratios at U.V. wavelengths between 200 and 210 nm. A known metabolite des-N-methylerythromycin is readily detectable using U.V. detection, whilst another metabolite/degradation product anhydroerythromycin is not seen using U.V. detection but is readily observable using an electrochemical detector. The method has a limit of sensitivity of 0.25 μg/mL and 1.00 μg/mL in serum and urine respectively (U.V. detection) and is sufficiently sensitive to monitor serum and urine concentrations of erythromycin in man after administration of a single 500 mg erythromycin stearate tablet. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1985
Influence of endogenous female sex-steroids on mutagen metabolism
- Authors: Goold, Richard David
- Date: 1985 , 2013-03-15
- Subjects: Mutagenesis , Drugs -- Metabolism , Steroid hormones -- Receptors , Cytochrome P-450
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3819 , http://hdl.handle.net/10962/d1004919 , Mutagenesis , Drugs -- Metabolism , Steroid hormones -- Receptors , Cytochrome P-450
- Description: Cytochrome P-450, the terminal oxidase of the metabolic mono-oxygenase system, is thought to exist in multiple forms, which have differing substrate specificities, and are variably inducible by different enzyme inducers. Many mutagens, themselves unreactive, require metabolic activation by one or more of these cytochrome P-450-dependent microsomal enzymes for mutagenic activity. Such mutagens may be detected in the Salmonella mutagenicity test only by the incorporation of an hepatic microsomal (59) fraction into the assay (as a first approximation to in vivo metabolism). Induction of the microsomal enzymes by different agents enhances the metabolic activation of mutagens; in fact, many mutagens are only detected when the 59 fraction has been induced by appropriate agents. Inducers of the phenobarbital-type are known to enhance microsomal steroid hydroxylation when administered at supraphysiological levels, inducers of several mono-oxygenase activities. In turn, the steroids, have been reported to be The inductive effects of the female sex-steroids and the combined effects of steroid and phenobarbital (PB) pretreatment on the metabolic activation of four mutagens have been investigated using the Salmonella assay. Female Sprague-Dawley rats were pret reated with 17a-oestradiol (E2) or progesterone (PRG) , at a level of either 1 mg/kg or 20 mg / kg daily for 14 days. A duplicate set of similarly pretreated groups were also induced with PB. Hepatic microsomal fractions were prepared from each group and incubated with each of the te st mutagens in the presence of a tester strain known to detect each particular type of mutagen. Induction of the hepatic metabolizing system by PB increased the activation of the mutagens significantly (as reflected by an increased number of revertant prototrophic S .typhimurium colonies). The administration of PRG also caused significant, and dose-dependent, induction of the activation of af l atoxin B1, benzo(a)pyrene, and dimethylnitrosamine. In general, E2 exhibited no inductive effect, but it did produce an increase in the activation of aflatoxin B1 (a reaction which is known to be catalysed by a mono-oxygenase prefe rentially inducible by PB). When use was made of a microsomal fraction that was prepared from animals which were both steroidpretreated and induced by PB, mutagenic activation was of the same order of magnitude as that observed when induction was brought about by PB alone. The absence of additive effect, taken together with the observations already mentioned, indicate that steroids induce the same cytochrome isozymes that are induced by PB. The implications of sex-hormonal regulation of the metabolic activation of mutagens are briefly discussed. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1985
- Authors: Goold, Richard David
- Date: 1985 , 2013-03-15
- Subjects: Mutagenesis , Drugs -- Metabolism , Steroid hormones -- Receptors , Cytochrome P-450
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3819 , http://hdl.handle.net/10962/d1004919 , Mutagenesis , Drugs -- Metabolism , Steroid hormones -- Receptors , Cytochrome P-450
- Description: Cytochrome P-450, the terminal oxidase of the metabolic mono-oxygenase system, is thought to exist in multiple forms, which have differing substrate specificities, and are variably inducible by different enzyme inducers. Many mutagens, themselves unreactive, require metabolic activation by one or more of these cytochrome P-450-dependent microsomal enzymes for mutagenic activity. Such mutagens may be detected in the Salmonella mutagenicity test only by the incorporation of an hepatic microsomal (59) fraction into the assay (as a first approximation to in vivo metabolism). Induction of the microsomal enzymes by different agents enhances the metabolic activation of mutagens; in fact, many mutagens are only detected when the 59 fraction has been induced by appropriate agents. Inducers of the phenobarbital-type are known to enhance microsomal steroid hydroxylation when administered at supraphysiological levels, inducers of several mono-oxygenase activities. In turn, the steroids, have been reported to be The inductive effects of the female sex-steroids and the combined effects of steroid and phenobarbital (PB) pretreatment on the metabolic activation of four mutagens have been investigated using the Salmonella assay. Female Sprague-Dawley rats were pret reated with 17a-oestradiol (E2) or progesterone (PRG) , at a level of either 1 mg/kg or 20 mg / kg daily for 14 days. A duplicate set of similarly pretreated groups were also induced with PB. Hepatic microsomal fractions were prepared from each group and incubated with each of the te st mutagens in the presence of a tester strain known to detect each particular type of mutagen. Induction of the hepatic metabolizing system by PB increased the activation of the mutagens significantly (as reflected by an increased number of revertant prototrophic S .typhimurium colonies). The administration of PRG also caused significant, and dose-dependent, induction of the activation of af l atoxin B1, benzo(a)pyrene, and dimethylnitrosamine. In general, E2 exhibited no inductive effect, but it did produce an increase in the activation of aflatoxin B1 (a reaction which is known to be catalysed by a mono-oxygenase prefe rentially inducible by PB). When use was made of a microsomal fraction that was prepared from animals which were both steroidpretreated and induced by PB, mutagenic activation was of the same order of magnitude as that observed when induction was brought about by PB alone. The absence of additive effect, taken together with the observations already mentioned, indicate that steroids induce the same cytochrome isozymes that are induced by PB. The implications of sex-hormonal regulation of the metabolic activation of mutagens are briefly discussed. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1985
A structural study of the capsular antigens of escherichia coli K36 and klebiella K68
- Authors: Stanley, Shawn Mark Ross
- Date: 1987 , 2013-03-11
- Subjects: Enterobacteriaceae , Klebsiella , Escherichia , Antigens
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3814 , http://hdl.handle.net/10962/d1004613 , Enterobacteriaceae , Klebsiella , Escherichia , Antigens
- Description: From Introduction: Bacterial cells all have a cytoplasmic membrane (see Figure 1) which regulates the movement of ions and molecules into and out of the bacterium. Enclosing this membrane is a cell wall of which there are two general types, which are differentiated by the Gram stain(02) as being either gram positive or gram negative (depending upon whether they hold the gram stain after washing with ethanol). The cell wall provides the cell with shape and rigidity and is composed, in the case of gram positive types, of peptidoglycan, and in the case of gram negative bacteria, of a peptidoglycan and an outer membrane (see Figure 2). The peptidoglycan layer, common to both cell wall types, consists of a backbone of alternating units of N-acetylglucosamine and N-acetylmuramic acid to which peptides are attached by amide links. This heteropolymer is a highly cross linked mosaic and this gives it strength and rigidity. In gram positive bacteria, this layer also contains two carbohydr ate antigens, a simple polysaccharide and a teichoic acid; these are usually the type specific or major group antigens of the bacterium. Many of the bacteria also produce exopolysaccharides (see Figure 3) either as discrete capsules (for example, the Enterobacteriaceae K antigens) or unattached slime layers (for example, the Enterobacteriaceae M antigens). The vast majority of these polysaccharides are heteroglycans(03) composed of contiguous oligosaccharide repeating units. Their monosaccharide components are largely neutral hexoses, 6-deoxy hexoses and also amino sugars. (03) Pentose units are rare. (03) The capsular polysaccharides usually have a high content of acidic constituents such as uronic acids, phosphate groups, or pyruvate ketals. (01) , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1987
- Authors: Stanley, Shawn Mark Ross
- Date: 1987 , 2013-03-11
- Subjects: Enterobacteriaceae , Klebsiella , Escherichia , Antigens
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3814 , http://hdl.handle.net/10962/d1004613 , Enterobacteriaceae , Klebsiella , Escherichia , Antigens
- Description: From Introduction: Bacterial cells all have a cytoplasmic membrane (see Figure 1) which regulates the movement of ions and molecules into and out of the bacterium. Enclosing this membrane is a cell wall of which there are two general types, which are differentiated by the Gram stain(02) as being either gram positive or gram negative (depending upon whether they hold the gram stain after washing with ethanol). The cell wall provides the cell with shape and rigidity and is composed, in the case of gram positive types, of peptidoglycan, and in the case of gram negative bacteria, of a peptidoglycan and an outer membrane (see Figure 2). The peptidoglycan layer, common to both cell wall types, consists of a backbone of alternating units of N-acetylglucosamine and N-acetylmuramic acid to which peptides are attached by amide links. This heteropolymer is a highly cross linked mosaic and this gives it strength and rigidity. In gram positive bacteria, this layer also contains two carbohydr ate antigens, a simple polysaccharide and a teichoic acid; these are usually the type specific or major group antigens of the bacterium. Many of the bacteria also produce exopolysaccharides (see Figure 3) either as discrete capsules (for example, the Enterobacteriaceae K antigens) or unattached slime layers (for example, the Enterobacteriaceae M antigens). The vast majority of these polysaccharides are heteroglycans(03) composed of contiguous oligosaccharide repeating units. Their monosaccharide components are largely neutral hexoses, 6-deoxy hexoses and also amino sugars. (03) Pentose units are rare. (03) The capsular polysaccharides usually have a high content of acidic constituents such as uronic acids, phosphate groups, or pyruvate ketals. (01) , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1987