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PubMed1996

Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (+/-)-calanolide A and its enantiomers.

The anti-HIV agent (+/-)-calanolide A (1) has been synthesized in a five-step approach starting with phloroglucinol [-->5-->6-->11-->18-->(+/-)-1], which includes Pechmann reaction, Friedel-Crafts acylation, chromenylation with 4,4-dimethoxy-2-methylbutan-2-ol, cyclization, and Luche reduction. Cyclization of chromene 11 to chromanone 18 was achieved by employing either acetaldehyde diethyl acetal or paraldehyde in the presence of trifluoroacetic acid and pyridine or PPTS. Luche reduction of chromanone 18 at lower temperature preferably yielded (+/-)-1. Reduction of chromone 12, synthesized by Kostanecki-Robinson reaction from chromene 11, failed to afford (+/-)-1. The synthetic (+/-)-1 has been chromatographically resolved into its optically active forms, (+)- and (-)-1. The anti-HIV activities for synthetic (+/-)-1, as well as resultant (+)- and (-)-1, have been determined. Only (+)-1 accounted for anti-HIV activity, which was similar to the data reported for the natural product, and (-)-1 was inactive.

Antiviral Agents↗
PubMed1997

Characterization of a new neurosecretory cell type containing gastrin-cholecystokinin-like peptide in the locust pars intercerebralis: ultrastructural and immunocytochemical studies, in situ and in vitro.

A new neurosecretory cell type of the locust pars intercerebralis, immunolabelled with an antiserum against a vertebrate peptide related to gastrin-cholecystokinin (CCK-8(s)), was characterized both in situ and in primary cell cultures. Semithin sections of pars intercerebralis were first immunostained in order to identify neurosecretory cells containing CCK-like material and then examined by electron microscopy. The neurosecretory cells containing CCK-like material were paraldehyde fuchsin negative and were unequivocally identified in ultrathin sections adjacent to immunostained semithin sections. They exhibited neurosecretory vesicles of variable electron density, ranging in diameter from 150 to 250 nm. Immunogold labelled ultrathin sections adjacent to unlabelled ultrathin sections allowed for the unambiguous localization of CCK-like immunoreactive material over the neurosecretory vesicles of the cells containing CCK-like material. Immunoreactivity towards CCK-8(s)-like peptide could also be detected in pars intercerebralis neurosecretory neurons grown in vitro. The CCK-like positive neurons showed a multipolar morphology with fine processes radiating from the cell body. The positive cells had the same ultrastructural characteristics as the in situ CCK-like neurons. The pattern of neurite outgrowth on reactive CCK-like neurosecretory cells in vitro and the neuroanatomical pathway of the CCK-like immunoreactive neurosecretory cells in situ could be correlated. On the basis of their number, size and localization in the locust pars intercerebralis, it is possible that the CCK-like neurosecretory cells correspond to neurosecretory cell type C, which has not, to date, been identified at the ultrastructural level.

Animals↗
PubMed1992

Detection and identification of volatile substances by headspace capillary gas chromatography to aid the diagnosis of acute poisoning.

Headspace gas chromatography with split flame-ionization-electron-capture detection is a simple method of screening for a wide range of volatile substances in biological fluids. A 60 m x 0.53 mm i.d. thick-film (5 microns) fused-silica capillary coated with SPB-1 (Supelchem) with split flame-ionization-electron-capture detection provides a valuable alternative to packed columns in this work. Most commonly abused compounds, including many with very low boiling-points such as bromochlorodifluoromethane (BCF), butane, dimethyl ether, FC 11, FC 12, isobutane and propane, can be retained and differentiated at an initial column temperature of 40 degrees C followed by programming to 200 degrees C. The total analysis time is 26 min. Retention and detector response data were generated for 244 compounds. Good peak shapes are obtained for polar analytes such as ethanol and injections of up to 0.30 cm3 of headspace can be performed with no discernable loss of efficiency. The sensitivity is thus at least as good as that attainable with packed columns. Of the commonly encountered compounds, only isobutane-methanol and paraldehyde-toluene are at all difficult to differentiate. Quantitative measurements can be performed either isothermally or by using the temperature programme.

Acute Disease↗
PubMed1999

Structured sedation programme for magnetic resonance imaging examination in children.

One thousand, eight hundred and fifty-seven patients underwent magnetic resonance imaging following the establishment of a structured sedation programme. Forty-eight of these patients came from the intensive care unit with a secure airway and were therefore excluded from any further analysis. Oral sedation was to be given to children aged 5 years and below. For children >/= 6 years old, oral sedation could be given only if their level of co-operation was judged to be inadequate by the referring physician. Oral sedation consisted of chloral hydrate 90 mg x kg-1 (maximum 2.0 g) orally with or without rectal paraldehyde 0.3 ml x kg-1. All magnetic resonance imaging requests for children who failed oral sedation as well as those referred for general anaesthesia from the outset were reviewed by a consultant anaesthetist who then allocated patients to undergo the procedure with either general anaesthesia or intravenous sedation. Scans requiring intravenous sedation or general anaesthesia were performed in the presence of a consultant anaesthetist. Intravenous sedation consisted of either a propofol 0.5 mg x kg-1 bolus followed by an infusion (maximum 3 mg x kg-1 x h-1) or midazolam 0.2-0.5 mg x kg-1 boluses. General anaesthesia was given using spontaneous ventilation with a mixture of 66% nitrous oxide in oxygen and isoflurane following either inhalation (sevoflurane) or intravenous (propofol) induction. One thousand and thirty-nine (57.4%) of the scans were done without sedation whereas 93 scans were performed during the consultant anaesthetist supervised sessions. Oral sedation failed in 50 out of 727 patients (6.9%). Eighty-seven per cent of children aged 5 years and below needed sedation compared with 4.5% of those aged over 10 years. Two patients who had only received chloral hydrate developed significant respiratory depression. This structured sedation programme has provided a safe, effective and efficient use of limited resources.

Adolescent↗
PubMed1999

Mania pre-lithium.

The changes that lithium brought are most fully understood when we grasp the difficulties for management that acute mania presented. Restraint in canvas camisoles, padded cells, paraldehyde, water-baths and salts-Epsom, not Lithium-met mania in echos of Bedlam still heard in the early 1950s. It is a part of psychiatric history important to remember.

Antimanic Agents↗
PubMed1981

Effects of anesthetic agents on synaptosomal GABA disposal.

In brain slices, halothane was shown to inhibit the metabolic breakdown of GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter. This inhibition leads to increased brain GABA content, presumably in the synaptic areas, and to the postulation that halothane anesthesia may arise from an enhanced synaptic inhibition due to this elevated GABA. The ability of many neurotropic agents to inhibit GABA breakdown was studied by assessing synaptosomal "GABA disposal". GABA disposal by intact synaptosomes, which simulate miniature synapses, measures the conversion of [1-14C]GABA to 14CO2 and includes the processes of uptake, release, and catabolism of GABA. The most potent inhibitor is chloroform, followed by halothane, enflurane, ether, and thiopental. Pentobarbital, ethanol, paraldehyde, and ketamine are weak inhibitors. Phenobarbital, morphine, and phenytoin are not inhibitory at pharmacologic concentrations. As a whole, anesthetic agents show particular inhibitory action on this metabolic process in this model system where the ID10 values (i.e., concentration of a drug necessary to produce 10 per cent inhibition of GABA disposal) correlate well with known pharmacologic potencies, ED50 values, or MACs. These observations support the possibility that anesthesia may be related to an inhibition of GABA disposal.

Anesthetics↗
PubMed1994

Clozapine for the control of hemiballismus.

Pharmacological agents used for the control of ballistic movements include chloral hydrate, barbiturates, paraldehyde, bromides, phenothiazines, progabide, haloperidol, pimozide, reserpine, tetrabenazine, sodium valproate, and dimethylaminoethanol. These agents are believed to act by different mechanisms, including modification of dopaminergic, GABAergic, or cholinergic mechanisms. We report a case where, after failure of haloperidol, phenobarbital, and pimozide, the hemiballistic movements were controlled with clozapine.

Adult↗
PubMedDate not supplied

Further histochemical studies characterizing the lipofuscin component of human neuromelanin.

The residuum of bleached substantia nigra neuromelanin and the nonoxidized and oxidized intraneuronal masses of inferior olive lipofuscin gave sudanophilic staining reactions with oil red O, Sudan black B, and a Sudan III and IV combination stain. The pigments also exhibited oxidation basophilia, each having been stained by Gomori's paraldehyde fuchsin method after bleaching or oxidation with potassium permanganate and by the modified carbol fuchsin method of Barbeito-Lopez after bleaching or oxidation with hydrogen peroxide or potassium permanganate. Confirmation of the presence of lipid substances in bleached neuromelanin was obtained by repeatedly staining, decolorizing, and restaining the residuum of the pigment when utilizing the chemically nonreactive beta naphthol type Sudan combination stain, Sudan III and IV. Not only were tinctorial properties characteristic of lipofuscin clearly demonstrated in the bleached residuum of neuromelanin, but additionally, a partial separation was achieved between the relatively soluble beta naphthol type Sudan-staining lipid component and an insoluble component, possibly lipoprotein, staining with Sudan black B and both basic fuchsin dye-containing mixtures. Consideration was given to the idea that the oxidation basophilia of these neuronal pigments was due to the oxidative formation or exposure of one or more kinds of acidic groups consisting of carboxyls or those containing sulfur or phosphorus.

Aged↗
PubMed1978

Identification of Gomori-positive glia in autoradiographs.

Unstained Gomori or paraldehyde fuchsin or chrome-haematoxylin-alum positive granules in the perikaria of so-called Gomori-positive glia of the periventricular zone of the rat hypothalamus, fixed with Bouin's or Carnoy's fluids, have been found to produce a positive chemographic (blackening) effect on autoradiographic emulsion. Similar action was produced by some granules in ependymal cells localized in the ventral part of the third ventricle between optical chiasma and median eminence. It is suggested that this positive chemographic effect can be employed for the identification and characterization of Gomori-positive glia in autoradiographic studies.

Animals↗
PubMed1989

Emergency management of seizures: an overview.

The drugs currently used in the emergency management of seizures are chiefly phenytoin, phenobarbital, diazepam, lorazepam, and paraldehyde. The combination of intravenous phenytoin and lorazepam has the advantages of rapid onset of action, sustained efficacy, and freedom from drug interactions. The intermittent oral or rectal administration of diazepam is especially useful for acute home treatment of recurrent seizures. Phenytoin prodrug (ACC-9653), an investigational new drug, is promptly absorbed after intramuscular injection. Unlike phenytoin, it does not require propylene glycol and high alkalinity for solubility and therefore does not produce soft-tissue injury after parenteral administration. It appears to be close to an ideal drug for the emergency management of seizures.

Diazepam↗
PubMed2000

Does status epilepticus influence the motor development of immature rats?

PURPOSE: To study the effect of severe status epilepticus (SE) on the motor development of rats. METHODS: SE was induced in 12-day-old rats (P12 group) and 25-day-old rats (P25 group) using the lithium-pilocarpine model. Seizures were interrupted after 2 hours by paraldehyde with an intraperitoneal dose of 0.3 or 0.6 mL/kg, respectively. Starting 3 days after SE, all animals were repeatedly exposed to a battery of motor and behavioral tests, including the bar-holding test, rotarod test, and open field test. RESULTS: In P12 animals, motor impairment occurred 2 months after SE, when significantly worse performance in the rotarod test was found. No difference between controls and experimental rats was found in any other test used. In contrast, P25 animals were significantly poorer in the bar-holding test from postnatal day 34 until adulthood. In open field study, P25 rats were found to be hyperactive during the whole period of testing, whereas P12 animals exhibited an initial period of hypoactivity (in the first test) that was replaced by hyperactivity that lasted until 2 months of age. In the last test performed at the age of 98 days, experimental P12 animals were again less active than age-matched controls. CONCLUSIONS: Animals of both age groups exhibited permanent changes of motor performance; however, both the pattern and the time course of these changes was related to age when SE was elicited.

Age Factors↗
PubMed1991

Status epilepticus: clinical experience with two special devices for continuous cerebral monitoring.

Continuous cerebral monitoring (CCM) was performed on 34 patients in status epilepticus (SE), using changes in amplitude detected by the cerebral function monitor (CFM) and changes in frequency detected by compressed spectral array (CSA). The EEG was used intermittently to help identify seizure patterns obtained with these methods. Seventeen patients in clinically manifest SE also had non-convulsive seizures. In 17 patients, SE was refractory to conventional anticonvulsants, requiring treatment with pentobarbital or paraldehyde. In these patients, CCM provided dynamic electroencephalographic monitoring of burst-suppression and prompt detection of breakthrough seizures. Patients in SE should undergo CCM to differentiate between non-convulsive seizures and post-ictal state both of which may produce prolonged unresponsiveness following clinical seizures. CCM after data reduction with the two special devices used is a viable and practical alternative to continuous conventional EEG monitoring during SE. However, in order to evaluate the sensitivity and specificity of these methods, it will be necessary to design a study in which both the EEG and the devices using data reduction be used continuously and concurrently.

Adolescent↗
PubMed1966

Inhibitory mechanisms in lateral geniculate nucleus of rat.

1. An examination was made of the mechanisms responsible for the inhibition of synaptic transmission through the lateral geniculate nucleus (LGN) of the rat following a single shock to the optic nerve.2. In the rat anaesthetized with paraldehyde we found no evidence that optic nerve stimulation produced any presynaptic inhibition in LGN. In agreement with other workers it was found that repetitive stimulation of visual cortex produced effects attributable to presynaptic inhibition. However, this was of small magnitude in the conditions of our experiments.3. Stimulation of the optic nerve elicited an action potential in a P cell (principal cell) which was followed by a wave of hyperpolarization lasting about 150 msec (inhibitory post-synaptic potential, IPSP, wave).4. The IPSP wave was chloride-dependent and was associated with inhibition of the P cell discharge. Occasional rippling on the IPSP wave suggests that it was produced by the repetitive discharge of I cells (interneurones).5. These observations support the model proposed previously wherein P cells are inhibited by I cells which in turn are excited by axon collaterals of P cells. There is evidence for diffuse interconnexions between P cells and I cells.6. The observation that the extracellularly recorded wave of hyperpolarization (P-wave) is usually negative suggests that most of the inhibitory synapses are not on the soma of the P cell.

Action Potentials↗
PubMed1983

Failure of intrathecal antitetanus serum to improve survival in neonatal tetanus.

In a prospective study, 161 infants with neonatal tetanus were randomised to receive (a) standard treatment, or (b) standard treatment together with intrathecal equine antitetanus serum, or (c) intrathecal antitetanus serum with systemic betamethasone. There was no difference in survival between the three treatment groups in infants with severe tetanus, but in mild tetanus those who received standard treatment alone had an improved survival rate. Parenteral intramuscular diazepam as a sedative was found to be preferable to paraldehyde, as the latter was associated with a higher incidence of secondary infections.

Betamethasone↗
PubMed1986

Hemodynamics of hemorrhage in the conscious rat and chicken.

Hemodynamic responses to hemorrhage in conscious chicks (n = 10, 233 g) and rats (n = 10, 309 g) were compared. The animals were fitted with miniature pulsed Doppler aortic flow probes 2 days (chickens) or 5 days (rats) before catheterization, and the experiment began 1 (chickens) or 2 (rats) days later. Mean arterial pressure (MAP) and cardiac output (CO) were recorded continuously and simultaneously digitized to compute total peripheral resistance (TPR). MAP, CO, and TPR values were graphed on-line by a microcomputer and stored for later analysis. A 4-ml hemorrhage reduced MAP and CO by 25 and 43% in the rat, and 15 and 4% in the chickens, respectively. The fall in CO in the rat was due to reduction of stroke volume (SV) unlike the birds where SV was well maintained. TPR was elevated 65% in the rats and fell 13% in the chickens. The minimal fall in CO and SV in these conscious birds suggests that anesthetic agents used previously (i.e., urethane, paraldehyde, phenobarbital, and pentobarbital sodium) suppressed cardiac function. However, they do not account for the lack of a peripheral vascular response during hemorrhage. The chicken apparently maintains MAP by a volume regulating mechanism operating independently of peripheral vascular tone inasmuch as circulating fluid volume restitution is rapid and occurs without vasoconstriction. The rat maintains MAP through reflex cardiac and peripheral vascular responses which eventually may contribute to transvascular fluid loss and the ultimate collapse after prolonged hemorrhagic hypotension.

Animals↗
PubMed1981

Serum potassium concentration in acidemic states.

It has been generally accepted that acidosis results in hyperkalemia because of shifts of potassium from the intracellular to the extracellular compartment. There is ample clinical and experimental evidence, however, to support the conclusion that uncomplicated organic acidemias do not produce hyperkalemia. In acidosis associated with mineral acids (respiratory acidosis, end-stage uremic acidosis, NH4Cl-or CaCl2-induced acidosis), acidemia per se, results in predictable increases in serum potassium concentration. In acidosis associated with nonmineral organic acids (diabetic and alcoholic acidosis, lactic acidosis, methanol and the less common forms of organic acidemias secondary to methylmalonic and isovaleric acids, and ethylene glycol, paraldehyde and salicylate intoxications), serum potassium concentration usually remains within the normal range in uncomplicated cases. A number of factors, however, may be responsible for hyperkalemia in some of these patients other than the acidemia per se. These include dehydration and renal hypoperfusion, preexisting renal disease, hypercatabolism, diabetes mellitus, hypoaldosteronism, the status of potassium balance, and therapy. The mechanism(s) of this differing effect of mineral and organic acidemias on transmembrane movement of potassium remains undefined. The prevalent hypothesis, however, favors the free penetrance of the organic anion into cells without creating a gradient for the hydrogen ions and, thus, obviating the efflux of intracellular potassium. The importance of the presence of hyperkalemia in clinical states of organic acidemias is obvious. A search for the complicating factors reviewed above should be undertaken since organic acidemias per se, should not be expected to be accompanied by elevations of serum potassium concentration. Moreover, the classical teaching that the absence of hyperkalemia during severe acidosis is indicative of severe potassium deficiency, may not be universally valid in patients with uncomplicated organic acidemias.

Acidosis↗
PubMed1983

ECT as a form of restraint.

ECT is controversial as a form of therapy, with lay and psychiatric objectors. Restraint is also controversial, though often necessary. The Ontario Mental Health Act of 1978 allows the psychiatrist to restrain patients without consent if there is risk of physical danger. The act mentions "chemical and mechanical" means. ECT is not dealt with as a form of restraint. A case is described of a manic male who during 2 episodes of psychosis presented a serious threat of assault to staff. The next of kin was reluctant to sign consent for "treatment" because of fear of the patient's later resentment. An application to the Review Board for permission to treat would have taken a week. On both occasions attempts to control the patient with chemotherapy were totally unsuccessful despite the use of rapid neuroleptization, paraldehyde, barbiturates and mechanical restraints. In both admissions 4 ECT given over 2 days produced rapid behavioural control. ECT was then discontinued because the patient declined to give consent for ECT as treatment and he no longer presented a threat. Medical and legal consultation were necessary and the consensus was that ECT as restraint may be justified on the basis of clinical judgment. In such cases ECT is safer, more reliable and more humane than chemotherapy or mechanical restraints. The authors discuss the current public and professional antipathy towards ECT. There is risk of death for the patient in circumstances where legal barriers prevent the appropriate use of electro-shock and a U.S. case is mentioned.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Continuous infantile spasms as a form of status epilepticus.

An infant with congenital cytomegalovirus infection first developed seizures at six weeks of age. At 3 1/2 months of age, he developed continuous infantile spasms that lasted for more than an hour. This episode of status epilepticus was terminated by intravenous lorazepam and paraldehyde, and seizures were subsequently controlled for seven months by adrenocorticotropic hormone (ACTH), valproic acid, and phenobarbital. This case demonstrates that continuous infantile spasms may occur as a unique form of status epilepticus in young infants.

Cytomegalovirus Infections↗