The views of public service managers on the implementation of National Health Insurance in primary care: a case of Johannesburg Health District, Gauteng Province, Republic of South Africa.

BACKGROUND: The South African government is implementing National Health Insurance (NHI) as a monopsony health care financing mechanism to drive the country towards Universal Health Coverage (UHC). Strategic purchasing, with separation of funder, purchaser and provider, underpins this initiative. The NHI plans Contracting Units for Primary healthcare (PHC) Services (CUPS) to function as either independent sub-district purchasers or public providers and District Health Management Offices (DHMOs) to support and monitor these CUPS. This decentralised operational unit of PHC, the heartbeat of NHI, is critical to the success of NHI. The views of district-level managers, who are responsible for these units, are fundamental to this NHI implementation. This qualitative study aimed to explore district and sub-district managerial views on NHI and their role in its implementation. METHODS: Purposive sampling was used to identify key respondents from a major urban district in Gauteng, South Africa, for participation in in-depth interviews. This study used framework analysis methodology within MaxQDA software. RESULTS: Three main themes were identified: managerial engagement in NHI policy development (with two sub-themes), managerial views on NHI (with three sub-themes) and perceptions of current NHI implementation (with six sub-themes). The managers viewed NHI as a social and moral imperative but lacked clarity and insight into the NHI Bill as well as the associated implementation strategies. The majority of respondents had not had the opportunity to engage in NHI policy formulation. Managers cited several pitfalls in current organisational operations. The respondents felt that national and provincial governments continue to function in a detached and rigid top-down hierarchy. Managers highlighted the need for their inclusion in NHI policy formulation and training and development for them to oversee the implementation strategies. CONCLUSIONS: It appears that strategic purchasing is not being operationalised in PHC. NHI policy implementation appears to function in a rigid top-down hierarchy that excludes key stakeholders in the NHI implementation strategy. The findings of this study suggest an inadequate decentralisation of healthcare governance within the public sector necessary to attain UHC. District managers need to be engaged and capacitated to operationalise the planned decentralised purchasing-provision function of the DHS within the NHI Bill.

Echocardiographic caudal vena cava measurements in healthy cats and in cats with congestive heart failure and non-cardiac causes of cavitary effusions.

BACKGROUND: Echocardiographic indices of the inferior vena cava have been associated with elevated right atrial pressures in humans. HYPOTHESIS/OBJECTIVES: Describe caudal vena caval (CVC) sonographic dimensions in healthy cats compared to cats with cardiogenic cavitary effusion (CCE), cardiogenic pulmonary edema (CPE), or non-cardiac causes of cavitary effusion (NCE). ANIMALS: 30 healthy control cats and 52 client-owned cats with CCE, CPE, or NCE examined at two university hospitals. METHODS: Sagittal 2-dimensional (2D) and M-mode CVC dimensions were acquired from the subxiphoid view. Caudal vena cava collapsibility index (CVC-CI) was calculated. Variables were compared between study groups using Kruskal-Wallis and Dunn's Bonferroni testing. Receiver operating characteristic curves were used to assess sensitivity and specificity for diagnostic categories. RESULTS: Healthy cats had sagittal 2D and M-mode (median, interquartile range) CVC maximal dimensions of 2.4 mm (1.3-4.0) and 3.4 mm (1.5-4.9) and CVC-CI of 52% (45.2-61.8) and 55% (47.8-61.3), respectively. The CVC maximal dimensions in healthy controls were smaller than in cats with cavitary effusions or pulmonary edema (all P<0.05). CVC-CI was different between CCE and NCE (P<0.0001) with cutoffs of CVC-CI ≤38% (2D) or ≤29% (M-mode) being 90.5% and 85.7% sensitive, and 94.4% and 100% specific for diagnosis of CCE, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Caudal vena cava measurements are larger in cats with cavitary effusions and cats with CPE than healthy cats. In cats with cavitary effusion, decreased CVC-CI, ≤38% (2D) or ≤29% (M-mode), was helpful in distinguishing between cardiogenic and noncardiogenic etiology.

Lifetime prevalence of mental health disorders and delay in treatment following initial onset: evidence from the Northern Ireland Study of Health and Stress.

BACKGROUND: The current study provides the first epidemiological estimates of lifetime mental disorders across NI based on DSM-IV criteria. Risk factors, delays in treatment and the experience of conflict are also examined. METHOD: Nationally representative face-to-face household survey of 4340 individuals aged > or =18 years in NI using the composite international diagnostic interview. Analyses were implemented using SAS and STATA software. RESULTS: Lifetime prevalence of any disorder was 39.1% while projected lifetime risk was 48.6%. Individuals who experienced conflict were more likely to have had an anxiety, mood or impulse-control disorder. Treatment delays were substantial for anxiety and substance disorders. CONCLUSIONS: Results from this study show that mental disorders are highly prevalent in Northern Ireland. The elevated rates of post-traumatic stress disorder in relation to other countries and the association of living 'in a region of terror' disorders suggests that civil conflict has had an additional impact on mental health. Given substantial delays in treatment, further research is required to investigate the factors associated with failure and delay in treatment seeking.

Cells in behaviourally relevant brain regions coexpress nuclear receptor coactivators and ovarian steroid receptors.

Oestradiol and progesterone act in the brain to elicit profound effects on behaviour and physiology. One physiological function of oestradiol is the induction of progesterone receptor (PR) expression in a variety of behaviourally relevant brain regions, including the ventromedial nucleus of the hypothalamus (VMN), the medial preoptic nucleus of the preoptic area (MPOA), the arcuate nucleus (ARC) and the medial central grey (MCG). Ligand-dependent transcriptional activity of steroid receptors, including oestrogen receptors (ER) and Pr, is dramatically influenced by nuclear receptor coactivators. In previous studies, we have found that two of these nuclear receptor coactivators, steroid receptor coactivator-1 (SRC-1) and CREB-binding protein (CBP), are important in ER-mediated induction of PR in the VMN and in steroid-dependent behaviours. For nuclear receptor coactivators to function in hormone-dependent transcription in the brain and regulate behaviour, both receptor and coactivator must be expressed in the same cell. In the present study, we used a dual-label immunohistochemical technique to investigate if individual cells in behaviourally relevant brain regions coexpress nuclear receptor coactivators and steroid receptors. Confocal analysis revealed that in oestrogen-primed rats, most of the E-induced PR cells in the VMN (89.6%), MPOA (63%), ARC (82.6%), and many in the MCG (39%), also express SRC-1. In addition, the majority of the cells containing E-induced PR in the VMN (78.3%), MPOA (83.1%), ARC (83.6%), and MCG (60%) also express CBP. These results, taken together with the findings that virtually all oestradiol-induced PR containing cells in the brain express ER, suggest that these neurones represent sites of functional interaction of nuclear receptor coactivators with ovarian steroid receptors in the brain. The present findings provide neuroanatomical evidence that nuclear receptor coactivators are integral in mediating steroid hormone action in behaviourally relevant brain regions.

Effect of diethylmaleate and other glutathione depletors on protein synthesis.

The alpha, beta-unsaturated carbonyl compound diethylmaleate (DEM) depletes glutathione (GSH) from liver and other tissues, and for this reason it is often used in toxicological research to study the GSH-mediated metabolism of xenobiotics. In addition to GSH depletion, however, DEM has been shown to have other nonspecific effects, such as alteration of monooxygenase activities or glycogen metabolism. In this study we found that DEM (1 ml/kg) inhibited protein synthesis in brain and liver, following in vivo administration to mice. Protein synthesis was measured as the incorporation of [3H]valine into trichloroacetic acid-precipitable material. Administration of DEM also decreased body temperature by 2-3 degrees. By increasing the environmental temperature from 22 degrees to 35 degrees the hypothermic effect of DEM was prevented, without affecting its ability to deplete GSH from brain and liver. Furthermore, when mice were maintained at 35 degrees, DEM still caused a significant decrease in protein synthesis, suggesting that this effect was only partially due to hypothermia. To test whether inhibition of protein synthesis was related to GSH depletion, groups of animals were dosed with the alpha, beta-unsaturated carbonyl phorone (diisopropylidenacetone) or the specific inhibitor of GSH synthesis, buthionine sulfoximine (BSO). Phorone decreased GSH in liver and brain; however, it had no effect on protein synthesis. BSO decreased GSH levels in liver and kidney, but not in brain, and did not have any effect on protein synthesis in any of these tissues, nor did it cause any hypothermia. Furthermore, when hepatic GSH content was decreased by in vivo administration of DEM or BSO, there was no inhibition of protein synthesis measured in vitro. These results indicate that, at the dose normally used to deplete GSH from various tissues. DEM also exerts an inhibitory effect on protein synthesis, which appears to be only partially due to its hypothermic effect, and is independent from GSH depletion. BSO, which, in our experimental conditions, lacks this and other nonspecific effects, might be a good alternative for studies aimed at characterizing the role of GSH in the metabolism and toxicity of chemicals.

Differential alterations of cholinergic muscarinic receptors during chronic and acute tolerance to organophosphorus insecticides.

Male mice treated for 2 weeks with the anticholinesterase insecticide disulfoton (O,O-diethyl S-[2-(ethylthio)-ethyl] phosphorodithioate; 10 mg per kg per day) became tolerant to the hypothermic and antinociceptive effects of disulfoton itself and of oxotremorine, a muscarinic cholinergic agonist. Homogenates of brain and ileum from tolerant animals exhibited reduced binding of the specific muscarinic antagonist [3H]quinuclidinyl benzilate ([3H]QNB). In forebrains of tolerant animals, the number of receptors (Bmax) was decreased 40% with no change in the affinity constant. Acetylcholinesterase (AChE) activity was 15% of control. Forty-eight hours after a single injection of disulfoton (10 mg/kg) mice were more resistant than their controls to the hypothermic and antinociceptive effects of a second administration of the same insecticide and of oxotremorine. Tolerance was not present 96 hr after a single administration of disulfoton. A single injection of disulfoton produced 74, 65 and 27% inhibition of AChE activity after 4, 48 and 96 hr respectively. Four hours after a second injection at 49 and 96 hr, 73 or 72% inhibition was found. [3H]QNB binding of animals treated with a single injection of disulfoton and of controls did not differ at either time point. An increase in the Ki for inhibition of [3H]QNB binding by unlabeled oxotremorine was observed in forebrain from mice killed 48 hr after a single injection of disulfoton, indicating a decreased affinity of the muscarinic receptor for agonists. Binding of [3H]oxotremorine-M was decreased significantly 48 hr after a single injection of disulfoton and after chronic treatment. It is suggested that a differential down-regulation of muscarinic receptors occurs in acute and chronic tolerance, involving agonist and antagonist binding sites and depending on duration of exposure.

Some concepts in toxicology.

Toxicology seeks to understand and quantify injurious chemico-biological interactions. The application of this understanding is prediction of the likelihood of occurrence of injury to human health or to undesirable alteration of ecological balance. The key to understanding chemical induced biological injury is development of improved methods of measuring changes in cellular function and structure and the application of these methods to elucidate the mechanisms and factors that modulate chemical injuries. The key to application of this understanding is appropriately designed dose-response and time-response studies which will, with appropriate consideration of biological mechanisms, allow prediction of conditions of exposure (and their confidence limits) that represent finite levels of risk of injury. The underlying data base required is extensive and will be drawn from traditional studies as well as new methods of testing and risk assessment.

Acute liver injury by vinyl chloride: involvement of endoplasmic reticulum in phenobarbital-pretreated rats.

A single 6-hr exposure to vinyl chloride monomer (5%) produces extensive vacuolization of centrolobular liver parenchyma and focal midzonal necrosis in the hepatic lobuole in phenobarbital-pretreated rats. Ultrastructurally, vacuolization consists of dilation of cysternae of rough endoplasmic reticulum and in the same cells smooth endoplasmic reticulum coalesces into discreet aggregates resembling denatured membranes. The findings support the hypothesis that vinyl chloride is hepatotoxic because it is converted into a toxic metabolite by components of the mixed function oxidase system of liver endoplasmic reticulum.

Biochemical toxicology of unsaturated halogenated monomers.

Previous inhalation toxicity studies from our laboratory have shown that 1,1-dichloroethylene (1,1-DCE), 1,1-dibromoethylene (1,1-DBE), and 2-chloro-1,3,-butadiene (2-CBD) are more toxic to fasted rats than to fed rats. Vinyl chloride monomer (VCM) and 1,1-difluoroethylene (1,1-DFE) were not acutely hepatotoxic at 46,500 and 82,000 ppm, respectively, in normal male rats, whether fed or fasted. On a molar basis, 1,1-DBE and 1,1-DCE have similar toxicities while 2-CBD is less toxic. All three compounds produce similar elevation of serum transaminase and bloody ascites, although at differing times following differing exposure concentrations. 1,1-DCE produces massive midzonal hepatic necrosis with hepatic thrombosis and chromatolysis within 2 hr after a 4 hr exposure of fasted rats to 200 ppm. Subsequent to formation of this midzonal lesion, the central portion of the lobule collapses, accompanied by congestion, ascites, and in increased hematocrit in the rat. Serum transaminase and sorbital dehydrogenase are greatly elevated at 6 hr. This effect in fasted rats is associated with glutathione (GSH) depletion. Diethyl maleate (DEM) which depletes GSH in fed rats potentiates the injury associated with 1,1-DCE exposure as well as that produced by 2-CBD. Rats fed ad libitum and exposed to 1,1-DCE or 2-CBD at night, a time of low hepatic GSH concentration, exhibit enhancement of hepatotoxic response when compared to animals exposed during the day when GSH is high.

Muscarinic receptor alterations following neostigmine treatment.

Male mice administered neostigmine in the drinking water a daily increasing concentrations (20-100 mg/l) for four days became tolerant to its toxicity and presented a reduced binding of [3H]quinuclidinyl benzilate ([3H]QNB) in the small intestine. An increased binding of [3H]QNB was found in the forebrains of neostigmine-treated animals. This was due to an increase in muscarinic cholinergic receptor density. Neostigmine-treated animals were also more sensitive than control to the hypothermic effect induced by oxotremorine. Dopaminergic and alpha- and beta-adrenoceptor were not affected. Administration of methylatropine together with neostigmine prevented the decrease of [3H]QNB binding in the small intestine as well as the increase in the forebrain.

Interaction of choline with muscarine receptor-stimulated phosphoinositide metabolism in the rat brain.

Previous receptor binding studies had shown that choline can interact with low potency with muscarine cholinoceptors. In the present study we have investigated whether choline is capable of functionally activating muscarine receptors by investigating its ability in stimulating the hydrolysis of phosphoinositides, a response believed to be coupled in brain to the M1 subtype of muscarine receptors. The results indicated that choline was only a very weak inducer of inositol phosphates (InsPs) accumulation in rat cerebral cortex slices as compared with acetylcholine or charbachol. Maximal increase of InsPs accumulation, at a choline concentration of 10 mM, was only 39 +/- 7%, as compared with the 4- to 6-fold stimulation induced by the other compounds. This effect of choline was not modified by physostigmine nor by the uptake inhibitor hemicholinium-3. At high concentrations, however, choline antagonized the stimulatory effect of acetylcholine and carbachol, suggesting that it might act as a partial agonist at this subtype of muscarine receptors, similar to what has been observed with oxotremorine. Choline had no effect on noradrenaline-stimulated InsPs accumulation.

Tolerance to the carbamate insecticide propoxur.

Male mice were given the carbamate insecticide propoxur (2-isopropoxy phenyl methylcarbamate; Baygon) in the drinking water at weekly increasing concentrations (from 50 to 2000 ppm), for a period of 6 weeks. At the end of the treatment the LD50 for propoxur was significantly higher in the treated animals as compared with controls. Propoxur-treated animals were also resistant to the hypothermic effect of an acute administration of the same compound. Groups of mice were challenged with the cholinergic agonist carbachol at intervals during the drinking water dosing and at its end. No differences in sensitivity to carbachol acute toxicity were found between control and treated animals. Propoxur-tolerant animals were also not resistant to the hypothermic effect of oxotremorine, another cholinergic agonist. [3H]Quinuclidinyl benzilate ([3H]QNB) binding (a measure of muscarinic receptor density and affinity) in forebrain, hindbrain and ileum never differed in control and treated mice. The possibility that repeated administrations of propoxur induced increased metabolic inactivation was tested by measuring hexobarbital sleeping time and carboxylesterase activity in treated and control mice. No changes in tissue carboxylesterase activities occurred but hexobarbital sleeping time was significantly reduced in propoxur treated animals suggesting an induction of hepatic microsomal enzymes. These results suggest that tolerance to propoxur is not mediated by a decrease of cholinergic receptors, as reported for other acetylcholinesterase inhibitors, but possibly by an enhancement of its metabolism.

Potentiation by triorthotolyl phosphate of acrylate ester-induced alterations in respiration.

The purpose of this study was to determine whether triorthotolyl phosphate (TOTP), an inhibitor of carboxylesterases, would enhance the inhibitory effects of acrylate esters on respiration. Respiratory frequency was measured and the calculated decreases in respiratory frequency were used as an index of respiratory irritancy due to acrylate compounds. Tidal volume, minute ventilation, and rectal temperature were also measured. Dose-dependent decreases in frequency were found in rats inhaling methyl acrylate, ethyl acrylate and acrylic acid. Tidal volume was also reduced in rats exposed to acrylate compounds and, as a result, the percentage change in minute ventilation was greater than the percentage change in frequency or tidal volume alone. Pretreatment with TOTP (125 mg/kg) enhanced the decreases in frequency and minute ventilation caused by acrylate esters but not those resulting from exposure to acrylic acid. Exposure to ethyl acrylate and acrylic acid also resulted in dose-dependent reductions in rectal temperature. TOTP potentiated ethyl acrylate-induced decreases in rectal temperature but not those caused by acrylic acid. The results suggest that inhibition of carboxylesterases can result in enhanced irritant action of acrylate esters on the upper respiratory tract, and provide support for a local role of carboxylesterases in the detoxification of these irritant esters.

Tolerance to anticholinesterase compounds in mammals.

Administration of multiple, sublethal doses of organophosphorus insecticides induces the development of tolerance to their toxicity. Among the different hypotheses investigated to explain the mechanism of this phenomenon, the one which has received the greatest experimental support is a downregulation of the muscarinic cholinergic receptors. Subsensitivity to cholinergic agonist has been demonstrated in vivo and in vitro in isolated organ preparations. Receptor binding experiments using muscarinic antagonists and agonists revealed a decrease of cholinergic receptors in central and peripheral tissues. Tolerance to another class of acetylcholinesterase inhibitors, carbamates has also been demonstrated. Differences from and similarities to organophosphate tolerance are discussed.

Trimethyltin inhibits uptake of neurotransmitters into mouse forebrain synaptosomes.

Trimethyltin (TMT), in a concentration dependent manner, inhibits in vitro uptake of gamma-aminobutyric acid (GABA), norepinephrine and serotonin by mouse forebrain synaptosomes with IC50S of 75, 43 and 24 microM, respectively. At 2 h and 14 h following in vivo administration of TMT (4.26 mg/kg; i.p.) to mice, GABA and serotonin uptake by forebrain synaptosomes are decreased, although norepinephrine uptake was not significantly affected. In vitro kinetic analyses of TMT inhibition of forebrain synaptosomal uptake of GABA, norepinephrine and serotonin indicated that the inhibition was not of the competitive type. This inhibition of uptake of neurotransmitters could be responsible, at least in part, for altered neurotransmitter levels in the synaptic cleft and may contribute to altered nervous system function during TMT intoxication.

The role of non-critical binding proteins in the sensitivity of acetylcholinesterase from different species to diisopropyl fluorophosphate (DFP), in vitro.

In vitro studies showed that organophosphate insecticides have different IC50 values (i.e., concentration of inhibitor required to inhibit 50% enzyme activity) for acetylcholinesterases (AChE's) from different species. Since previous reports indicated that the binding of active cholinesterase inhibitors to non-critical binding proteins is an important mechanism of detoxification of organophosphate insecticides in vivo, we investigated the role of non-critical binding proteins in synaptosomal membrane preparations from monkey, rat and chicken brain tissues as a possible explanation of the differences in the IC50's. The amount of non-critical binding proteins as well as critical binding sites, AChE, were determined by 3H-DFP binding in vitro. The affinity constants (Ka) and phosphorylation constants (Kp) of DFP for AChE's from these preparations were also determined by kinetic studies. In IC50 studies, monkey brain AChE was 1.5X and 3.2X more sensitive to DFP inhibition than chicken and rat brain AChE. The observed differences in IC50's cannot be explained on the basis of differences in the amount of non-critical binding proteins, since only small amount of non-critical binding proteins were found in these preparations. However, in the kinetic studies, monkey brain AChE had 3.7X and 2.1X higher affinity than chicken and rat brain AChE, respectively; and chicken brain AChE had about 2.7X faster rate of phosphorylation than the other two. It is therefore concluded that non-critical binding proteins are relatively unimportant in terms of affecting IC50's. The differences observed in IC50's are primarily due to different affinity and/or rate of phosphorylation of AChE active sites by DFP.

Reduced muscarinic receptor binding in tissues of rats tolerant to the insecticide disulfoton.

Tolerance to the toxic effects of exposure to the organophosphate acetylcholinesterase inhibitor, disulfoton, was induced by giving multiple, sublethal doses of the compound to male rats. Tolerance was judged to have been induced when toxic signs of exposure, including weight loss, were reversed or diminished. Binding of the specific muscarinic radioligand, [3H] quinuclidinyl benzilate ([3H] QNB) to ileal muscle, forebrain, and hindbrain from treated animals was significantly less than the amount bound to tissue from the control animals. Binding of [3H] QNB to heart tissue from tolerant animals was not different from control values. After a typical tolerance-inducing regimen of 7 doses of 2 mg/kg/day disulfoton followed by 4 doses of 3 mg/kg/day, [3H] QNB binding to heart from treated animals was 104% of controls, while binding to ileal muscle, forebrain, and hindbrain was 67, 69, and 77% of control values (p less than .001, .001 and .01), respectively. [3H] QNB binding was not decreased due to competition for binding sites with excess acetylcholine. Neither were decreases due to displacement by disulfoton, as an acute dose of disulfoton (which caused marked inhibition of acetylcholinesterase) did not result in decreased binding. The maximal binding (Bmax) to forebrain of tolerant animals was 56% of control (1.06 vs 1.88 pmol [3H] QNB mg protein-1, p less than 0.01), but no statistically significant change could be seen in equilibrium dissociation constants (Kd, 0.35 vs 0.36 nM). No changes in [3H] QNB binding constants occurred in hearts form tolerant animals. Differences between tolerant and control groups could be seen in [3H] QNB binding to striatum, but no alterations occurred in this brain area in the binding of dopaminergic or gabaergic radiolabels. The data presented in consistent with the hypothesis that cholinergic receptors are involved in organophosphate tolerance.

Antinociceptive and hypothermic effects of trimethyltin.

Trimethyltin (TMT) induced a dose-dependent antinociceptive and hypothermic effect in mice. Antinociception was not attenuated by naloxone but was reversed by atropine. TMT, however, was ineffective in displacing (3H)-QNB binding in vitro and did not affect (3H)-QNB binding or acetylcholinesterase activity after in vivo administration. The ethyl ester of nipecotic acid, a specific inhibitor of synaptosomal GABA uptake, exerted a similar antinociceptive effect that could be blocked by atropine. The GABA receptor antagonist bicuculline attenuated antinociception induced by TMT and nipecotic acid ethyl ester but not by morphine or oxotremorine. Gamma-Vinyl GABA, an irreversible inhibitor of GABA metabolism, prolonged TMT but not morphine-induced antinociception. In contrast, neither the dose-response nor the time course of TMT-induced hypothermia were affected by any of the drugs tested. The findings suggest that the GABAergic system may be involved in TMT induced antinociception; however, the mechanism responsible for the hypothermic effect of TMT is not apparent.

Chronic administration of an organophosphorus insecticide to rats alters cholinergic muscarinic receptors in the pancreas.

Male rats were treated for 10 days with the organophosphorus insecticide, acetylcholinesterase inhibitor, O,O-diethyl S-[2-(ethylthio)ethyl] phosphorodithioate (disulfoton, 2 mg/kg/day by gavage). At the end of the treatment, binding of [3H]quinuclidinyl benzilate ( [3H]QNB) to cholinergic muscarinic receptors and cholinesterase (ChE) activity were assayed in the pancreas. Functional activity of pancreatic muscarinic receptor was investigated by determining carbachol-stimulated secretion of alpha-amylase in vitro. ChE activity and [3H]QNB binding were significantly decreased in the pancreas from disulfoton-treated rats. The alteration of [3H]QNB binding was due to a decrease in muscarinic receptor density with no change in the affinity. Basal secretion of amylase from pancreas in vitro was not altered, but carbachol-stimulated secretion was decreased. The effect appeared to be specific since pancreozymin was able to induce the same amylase release from pancreases of control and treated rats. The results suggest that repeated exposures to sublethal doses of an organophosphorus insecticide lead to a biochemical and functional alteration of cholinergic muscarinic receptors in the pancreas.

Effect of trimethyltin on chemically-induced seizures.

The effect of trimethyltin (TMT; 4.26 mg/kg i.p.), at 1 and 14 h following administration, on chemically-induced seizures in mice is reported. At 1 h following administration, TMT decreased seizure responsiveness and protected animals from bicuculline, isonicotinic acid hydrazide (INH) and pentylenetetrazol (PTZ) induced seizures. At 14 h following administration, TMT provided little protection against bicuculline, INH or PTZ induced seizures. Only slight decreases in seizure responsiveness were observed with strychnine induced seizures at either 1 or 14 h. By 16 h following administration, animals exhibited spontaneous tremors and convulsions. The results indicate that TMT exerts a biphasic effect on central nervous system excitability.