Metabolic defects caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and by HPTP (the tetrahydropyridinyl analog of haloperidol), in rats.

The results of previous studies in the baboon have suggested that HPTP, the tetrahydropyridinyl analog of haloperidol causes a urinary biochemical marker profile similar to those seen in humans suffering from inborn errors of mitochondrial respiration. In order to identify a possible relationship between compromised cellular energy production and neuronal damage we now have compared the urinary profiles of rats treated with the pro-neurotoxin, MPTP as well as with HPTP. Significantly increased urinary excretion of lactic acid and 2-ethylhydracrylic acid in MPTP and HPTP treated rats was observed, indicating that both MPTP and HPTP and/or their respective metabolites cause mitochondrial inhibition in the rat.

Neuropharmacology of paradoxic weight gain with selective serotonin reuptake inhibitors.

It has been suggested that weight gain associated with tricyclic antidepressants (TCA) reflect actions on dopamine (DA) and histamine receptors. However, a definitive cause is purely assumptive given the nonselective pharmacology of these agents. The selective serotonin reuptake inhibitors (SSRIs), as well as agents like dexfenfluramine (DFF), have emphasized the pivotal role of serotonin (5HT) in reducing carbohydrate (CHO) intake, and have provided a more selective tool with which to study appetite regulation.

Solubility and dissolution properties of generic rifampicin raw materials.

Rifampicin shows polymorphism; therefore, it is necessary to select a suitable crystal form at an early stage of development to ensure optimum solubility and dissolution rates. This study was an investigation into the crystal properties of several rifampicin raw materials currently being used by manufacturers of generic rifampicin raw materials in South Africa. Powders were characterized by X-ray diffraction (XRD), infrared (IR) spectroscopy, and differential scanning calorimetry (DSC).

Structure-activity relationships of polycyclic aromatic amines with calcium channel blocking activity.

8-Benzylamino-8, 11-oxapentacyclo[5.4.0.

The utilization of alanine, glutamic acid, and serine as amino acid substrates for glycine N-acyltransferase.

The conjugation of benzoyl-CoA with the aliphatic and acidic amino acids by glycine N-acyltransferase, as well as the amides of the latter group, was investigated. Bovine and human liver benzoyl-amino acid conjugation were investigated using electrospray ionization tandem mass spectrometry (ESI-MS-MS). Bovine glycine N-acyltransferase catalyzed conjugation of benzoyl-CoA with Gly (Km(Gly) = 6.

Cerebral blood flow effects of the nitric oxide donor, nitroglycerin and its drug combinations in the non-human primate model.

Nitroglycerin (CAS 55-63-0, Nitrocene) has successfully been used in the management of angina during the last several decades. Although important information on the pharmacological actions and efficacy of nitroglycerin have been extracted, to date, limited research has been conducted on its effects on cerebral blood flow. In recent years, with the aid of SPECT (single photon emission computed tomography) and PET (positron emission tomography) it has been shown that marked cerebral blood flow changes occur under treatment of a wide variet of drugs.

A survey of the treatment of female patients with osteoporosis using drug utilization consumption parameters.

Objective: To investigate the drug treatment of female patients who were diagnosed with osteoporosis in South Africa using drug utilization consumption parameters.

Method: Prescription data over a 2-year period for 1655 female patients with osteoporosis were analysed retrospectively.

Results: A total of 157,245 products at a cost of R15,004,643.

Haemodynamic changes in the cardiovascular system during the early phases of orthostasis.

In this study, we monitored the changes in arterial blood pressure continuously in two groups of Caucasian men during normal passive orthostasis as well as reversed passive orthostasis. Group A consisted of a group of 23 younger men (16 +/- 0.5 years) and group B consisted of 21 older men (62.

Effect of the degree of quaternization of N-trimethyl chitosan chloride on the permeability of intestinal epithelial cells (Caco-2).

N-trimethyl chitosan chloride (TMC), a partially quaternized derivative of chitosan with superior water solubility, was synthesized with different degrees of quaternization [12.6% quaternized (TMC-L) and 19.9% quaternized (TMC-H)] and the effects of these novel polymers on the permeability of intestinal epithelial cells were investigated in Caco-2 cell monolayers.

Identifying and developing rugby talent among 10-year-old boys: a practical model.

The re-entry of South Africa into the international sporting arena and the resultant need for the identification and development of talent, especially among formerly deprived groups of people, provided the incentive for this study. Its aim was to identify the physical, motor and anthropometric variables that will enable coaches to identify 10-year-old boys, based on their abilities, who could become successful rugby players. Altogether, 173 ten-year-old boys with no rugby experience from a cross-section of the population were selected at random and subjected to 14 physical and motor tests and 14 anthropometric measurements.

Possible mechanisms through which dietary pectin influences fibrin network architecture in hypercholesterolaemic subjects.

It is suspected that not only fibrinogen concentration but also the quality of fibrin networks may contribute to cardiovascular risk. Evidence is accumulating that a "prudent" diet may protect against diseases associated with raised clotting factors. The effect of diet on fibrinogen is, however, still controversial.

An investigation into antidiabetic medication prescribing in South Africa.

Background: The number of people with diabetes in Africa is expected to triple in the next 15 years, which will have a significant impact on the prescribing and use of antidiabetic medication.

Objective: The primary aim of this study was to investigate the prescribing patterns of antidiabetic medication that are used on a chronic basis in South Africa.

Method: Prescribing data of 1100 diabetic patients were retrospectively analysed over a 1-year period.

Enhancement of paracellular drug transport with highly quaternized N-trimethyl chitosan chloride in neutral environments: in vitro evaluation in intestinal epithelial cells (Caco-2).

Previous studies have established that a partially quaternized derivative of chitosan, N-trimethyl chitosan chloride (TMC), can be used as an absorption enhancer for large hydrophilic compounds across mucosal surfaces. This study evaluates and compares the effects of the degree of quaternization of TMC, in a neutral environment, on the permeability of intestinal epithelial cells in vitro, where normal chitosan salts are ineffective as absorption enhancers. The effects of TMC-H [61.

A study of the changes during heating of paracetamol.

The orthorhombic form of paracetamol has been shown to exhibit greater compressibility and faster dissolution than the monoclinic form. The orthorhombic form is produced by melting of monoclinic crystals of paracetamol followed by cooling at specific rates. Cooling rate, although a very important factor, is not the only factor influencing the formation of either of the two morphs.

Cerebral blood flow effects of sodium valproate in drug combinations in the baboon model.

Sodium valproate (CAS 1069-66-5, Epilim) has been used in the management of epilepsy during the last three decades. Although important information on the pharmacological actions and efficacy of sodium valproate has accrued to date, limited research has been conducted on its effects on cerebral blood flow. In recent years, with the aid of SPECT (single photon emission computed tomography) and PET (positron emission tomography) it has been shown that marked cerebral blood flow changes occur in epileptic patients.

Chitosan for enhanced intestinal permeability: prospects for derivatives soluble in neutral and basic environments.

In this study the effects of two chitosan salts, namely chitosan hydrochloride and chitosan glutamate (0.5 and 1.5% w/v), on the transepithelial electrical resistance (TEER) and permeability of Caco-2 cell monolayers, using the radioactive marker [14C]-mannitol, were investigated in a slightly acidic (pH 6.

Comparison of the effect of different chitosan salts and N-trimethyl chitosan chloride on the permeability of intestinal epithelial cells (Caco-2).

A partially quaternized chitosan derivative, N-trimethyl chitosan chloride (TMC) (degree of quaternization 12.28%), was synthesized and the effects of this novel polymer on the permeability of intestinal epithelial cells, using Caco-2 cell monolayers, were investigated and compared with those of chitosan hydrochloride and chitosan glutamate. Transepithelial electrical resistance (TEER) measurements at pH 6.

Lecithin has no effect on serum lipoprotein, plasma fibrinogen and macro molecular protein complex levels in hyperlipidaemic men in a double-blind controlled study.

Objective: To examine the effects of lecithin on serum lipoprotein, plasma fibrinogen and macro molecular protein complex (MPC) levels.

Subjects And Study Design: Twenty free living hyperlipidaemic men participated in this double-blind study which controlled for possible indirect effects. The subjects were randomly assigned to one of three treatments: frozen yoghurt or frozen yoghurt with 20 g soya bean lecithin or frozen yoghurt with 17 g sunflower oil.

A new method for determining affinity constants on isolated organs when a threshold value and spare receptors are present.

It was shown in previous studies that fixed ratio combinations of agonists with competitive antagonists emulate partial agonists and, therefore, mediate submaximal concentration-effect (E/[A]) curves. A linear plot was obtained by plotting the relative height (H) of these submaximal curves against phiH, where phi=[antagonist]/[agonist]. In this study, it was shown that in an agonist-effector system comprising a possible threshold value, the use of fixed ratio agonist-competitive antagonist concentrations (artificial partial agonists) induces E/[A] curves of different heights which allows one to quantify the threshold value.

Determination of epidermal transpiration in four cultivars of Nicotiana tabacum L. using epidermal strips in a quasi-steady state system.

A quasi-steady state method is presented for quantifying epidermal transpiration of epidermal strips where simple relations between transmembrane fluxes and parameters of diffusibility of penetrating compounds hold. Contrary to most permeability studies, we did not use astomatous, enzymatically isolated, or dried cuticular membranes, because these procedures are largely responsible for the problems cited in the literature. Instead, we used freshly harvested stomatous epidermal strips, thus avoiding the sorption of lipids by the cuticular membranes during enzymatic isolation.

Carnitine palmitoyltransferase I activity monitoring in fibroblasts and leukocytes using electrospray ionization mass spectrometry.

Carnitine palmitoyltransferase I (CPT I) is one of the enzymes associated with normal mitochondrial membrane transport of certain metabolites. The importance of the enzyme in normal energy production is well illustrated during fasting conditions when a large flux of long-chain fatty acids must be transported over the mitochondrial membrane to undergo beta-oxidation. Up to now CPT I activity has been assayed in various tissues, including liver, leukocytes, platelets, and fibroblasts by the use of an isotope exchange forward assay which measures the rate of palmitoyl-l-[methyl-3H]carnitine formation from palmitoyl-CoA and l-[methyl-3H]carnitine.

The endocrine pancreas of the Cape fur seal, Arctocephalus pusillus (Schreber, 1776): an immunocytochemical study.

The indirect peroxidase method was employed to study the endocrine pancreas of the Cape fur seal. Immunoreactivity to insulin was confined to the cores of the islets and the insulin cells were more abundant than the other endocrine cell types, which occurred mainly in the mantles of the islets. Of these, glucagon cells were the most numerous, followed by somatostatin and pancreatic polypeptide (PP) cells.

N-trimethyl chitosan chloride as a potential absorption enhancer across mucosal surfaces: in vitro evaluation in intestinal epithelial cells (Caco-2).

Purpose: Previous studies have established that chitosan hydrochloride and glutamate are potent absorption enhancers for large hydrophilic compounds across mucosal surfaces. However, these compounds lack solubility at neutral pH values. A partially quaternized and well-soluble derivative of chitosan, N-trimethyl chitosan chloride, was synthesized and the effects of this polymer on the transepithelial electrical resistance and permeability of intestinal epithelial cells were investigated in vitro.

Effect of the haloperidol tetrahydropyridine metabolite 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3,6- tetrahydropyridine on dopamine receptor and transporter binding. A nonhuman primate 123I-iodobenzamide and 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane single photon emission computed tomographic study.

Researching the biological activities and toxicities of metabolites of drugs is of growing importance and has received increasing attention during the last decade in order to gain a better understanding of the efficacy and safety profile of drugs in clinical use. HPTP (4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3, 6-tetrahydropyridine, CAS 52669-92-8), the tetrahydropyridine metabolite of the classical neuroleptic, haloperidol (CAS 52-86-8), has recently been the focus for further understanding the well-known side effect profile of haloperidol. The current study was aimed at investigating the effect of HPTP treatment on dopamine receptor and transporter binding in the nonhuman primate, i.

Diet and haemostasis: time for nutrition science to get more involved.

Abnormal haemostasis, and specifically a pre-thrombotic state characterized by hypercoagulability, increased platelet aggregation and impaired fibrinolysis, is associated with increased atheroma and thrombosis. The recent literature clearly indicates that diet may prevent or be used to treat some abnormal haemostatic states. There are reports on effects of energy intake and expenditure, alcohol consumption, intakes of total fat, different fatty acids, fish oil, NSP and vitamins on markers of coagulation, platelet function and fibrinolysis.