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Biomedical subjects

C F Chen

Publications and source records attributed to C F Chen.

At least 343 records · Page 19Linked to original sources

Role of glial cation and anion transport mechanisms in etiology and arrest of seizures.

The intrinsic processes involved in the initiation and arrest of seizures are not completely understood. Cortical and cerebellar inhibitory mechanisms, accumulation of metabolic products, and glial uptake of extracellular potassium (K+o), anions, and released neurotransmitters are all important processes that limit focal firing and terminate a seizure once it has been initiated. Of these, the intrinsic cortical inhibitory mechanisms--i.e., recurrent and surround inhibition--appear to be the most important. Active cation and anion transport processes are two metabolic events that have yet to be elucidated but clearly could be involved in terminating a seizure discharge. For example, without an active mechanism to transport chloride, opening of the chloride channel by the inhibitory transmitter GABA would not result in increased chloride permeability. The transient hypoxia and hypercapnia and lactic acidosis that follows a severe tonic-clonic seizure produces a mixed systemic metabolic and respiratory acidosis. In experimental animals, the hypercapnia that results is sufficient to block seizure discharges. Increasing the CO2 concentration significantly reduces the extension to flexion (E/F) ratio of mice given maximal electroshock seizures (MES) and increases the time required for 50% of the animals to recover sufficiently from a first MES to be able to have another MES. The decreased E/F ratio and the increased recovery time (RT50) are both indicative of a decrease in seizure activity. Since the extent to which CO2 is allowed to accumulate in the brain is regulated by the glial specific enzyme carbonic anhydrase (CA), it follows that the glial cell has an integral role in the mechanisms involved in arresting seizure activity. In contrast, hypoxia increased the E/F ratio and decreased the RT50, evidence that seizure activity was enhanced. Another metabolic factor affecting duration of seizure activity, susceptibility to seizures, and recovery from seizures is glucose. Recovery from seizures depends in part on an adequate supply of this energy source. An inverse correlation (R = 0.95) between RT50 and blood sugar was found when the blood sugar was altered experimentally by treatments that altered the endocrine status (pancreatectomy, treatment with alloxan, cortisol, insulin, glucagon, and dextrose). Since glial cells contain (as glycogen) the small amount of glucose present in the brain, they probably hasten the ability of the brain to recover normal function following a seizure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Drug sensitivity of methylnitrosourea- and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea-resistant L1210 lines.

Drug sensitivity of methylnitrosourea (MNU)- and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU)-resistant L1210 lines have been compared. In the production of the MeCCNU-resistant line full resistance to MeCCNU was obtained after 15 generations with a gradual increase of the treatment dose. Treatment of L1210 with MNU (40 mg/kg i.p. on days 1, 3, and 5) produced after five or more treatment generations a MNU-resistant subline with reduced tumor growth in the untreated controls. Therapeutic responses of L1210, L1210-MeCCNU and L1210-MNU to MeCCNU, MNU, cyclophosphamide, 2,2'-dichloro-N-methyldiethylamine hydrochloride, 1-beta-D-arabinofuranosylcytosine, methotrexate, and 6-mercaptopurine were compared in both non-and X-irradiated (400 R) mice. The L1210 and L1210-MeCCNU lines reacted similarly except that L1210-MeCCNU was resistant to Me-CCNU and MNU. However, the L1210-MNU line differed greatly from the parent line. The survival times in nonirradiated mice were increased in all except the MNU- and MeCCNU-treated groups, and in irradiated mice they were less than 30 days and only cyclophosphamide and 2,2'-dichloro-N-methyldiethylamine hydrochloride caused long-term survivors. The different behavior of L1210-MNU and L1210-MeCCNU is apparently due to the fact that at maximum tolerated doses the monofunctional alkylating agent MNU is more mutagenic than the bifunctional MeCCNU. Antigenic change and loss of growth potential presumably are the reasons for the different sensitivity of L1210-MNU as indicated by tests in X-irradiated and nude mice. Apparently this host-related sensitivity is not directly related to the development of drug resistance.

Alkylating Agents↗

Spinal cord injuries in Taipei, Taiwan, 1978-1981.

This survey of spinal cord injuries in Taipei city from January 1978 to December 1981 was carried out by a review of the hospital records. During these four years 560 patients with acute spinal cord injury (SCI) were admitted to the hospitals in the city of Taipei. Of these, 123 were inhabitants of Taipei city, showing the annual incidence of SCI in Taipei to be 14.6 per million population. As a result of injury 118 patients were paraparetic, 180 were paraplegic, 117 tetraparetic and 145 were tetraplegic. The average age was 36 years and 2 months and one third were in the 20 to 29 year age group. The male/female ratio was 4.9. The causes of SCI were traffic accidents (44.5%), accidental falls (28.5%), struck by object (14.6%) and sports injury (3.4%). The mortality rate was 6.0%. Respiratory complication was the leading cause of death, accounting for 58% of the total deaths.

Accidents↗

Cardiovascular effects of matrine isolated from the Chinese herb Shan-dou-gen.

Matrine, a pure compound isolated from the Chinese herb Shan-don-Gen (Sophora subprostrata), was studied for its effects on the cardiovascular system of the rat. Intravenous injections of matrine at doses from 5 mg to 20 mg/kg body weight exhibited dose-dependent hypotensive and bradycardiac effects. These effects lasted only 1 to 3 min. In the isolated atria and ventricle preparations, matrine at doses from 50 micrograms to 200 micrograms/ml increased the amplitudes of spontaneous contraction of the atria and electrically induced contraction of the ventricle, whereas the frequency of the spontaneous beating of the atria was reduced. The dose-dependent effects of matrine on the isolated preparations persisted as long as the compound was present. Tachyphylaxis was not observed with repeated applications of this compound to the isolated preparations. The positive inotropic effects on both atria and ventricle and the negative chronotropic effect on spontaneous beating of the atria by matrine were not blocked by diphenhydramine, atropine, phenoxybenzamine, propranolol, trifluoperazine, or methysergide. In contrast, verapamil significantly reduced the positive inotropic effect of matrine on the ventricle. In the isolated aortic strip preparation, matrine at a dose of 200 micrograms/ml led to a slight increase in muscle tone. The same dose of matrine induced a 35% increase of perfusion pressure in the hindleg perfusion model. These results suggest that the in vivo transient hypotensive effect of matrine is likely associated with a decrease in heart rate itself, since positive inotropic effects on both the atria and the ventricle, and vasoconstriction of some vascular beds could not be the cause of hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗

Ionic and acid-base regulation of neurons and glia during seizures.

Much evidence shows that glia regulates the cation and anion content of brain interstitial space. In rats the pH and bicarbonate (HCO3-) concentration of neurons and glia were derived from carbon 14-labeled HCO3- and dimethyloxazolidinedione uptake into brain and cerebrospinal fluid. Acetazolamide increases the total CO2 concentration in neurons and decreases the pH and HCO3- concentration in glia. Inhibition of glial carbonic anhydrase (CA) reduces conversion of neuronally derived CO2 to HCO3-, glial pH is lowered, and neuronal CO2 accumulates. CA therefore has an essential role in regulating pH in neurons, glia, and interstitial fluid. In audiogenic seizure mice, glial CA activity is increased and glial anion transport is reduced. As the mice age, seizure susceptibility, the increased CA activity, and the defect in anion transport disappear concurrently. The enhanced CA activity in the glial cells of these mice is an adaptive mechanism to overcome the defect in anion transport that results from a deficiency of HCO3- -dependent and Na+- and K+ -dependent adenosine triphosphatase. Pentylenetetrazol stimulates neurons in neonatal rats, but after 10 days of age, when glia is present, it too is stimulated and the seizures are attenuated. Cobalt implantation in the cortex of rats also induces a glial response that ameliorates the focal seizures produced by this procedure.

Acid-Base Equilibrium↗

The renal, cardiovascular and hemolytic actions in the rat of a toxic extract from the bile of the grass carp (Ctenopharyngodon idellus).

Grass carp bile, sometimes eaten by Chinese people, has previously been shown to induce acute renal failure in man and to result in the death of experimental mice and rats. A toxic extract from the bile acid fraction of grass carp bile (LD50 109 mg/kg) was injected into pentobarbitone anesthetized rats and an increase in urinary excretion of water and salts was produced. The bile extract also caused a prompt fall in systemic arterial blood pressure and cardiac output. It was also found, in vitro, that the bile salts caused a potent hemolysis. The hypothesis that hemoglobin is released from hemolysed red blood corpuscles and might be responsible for the long term renal functional damage is considered. Another alternative hypothesis is that the hypotension induced by the bile toxin may result in renal underperfusion and thus make the kidney more susceptible to the nephrotoxic action of the grass carp bile.

Animals↗

Both dopaminergic and adrenergic receptors in the brain are involved in the behavioural excitation induced by dibutyryl 3',5'-adenosine monophosphate and aminophylline in the rat.

Following administration of dibutyryl cyclic-AMP or aminophylline, but not vehicle solution, into the lateral cerebral ventricle of rats produced locomotor stimulation, head and body rearing, circling, (as indicated by an enhancement of gross movement), increased grooming, head swaying and scratching (as indicated by an enhancement of fine movement), tail elevation, piloerection and convulsion. The behavioural excitation produced by either dibutyryl cyclic-AMP or aminophylline was antagonized by pretreatment with intraventricular injection of either two alpha-adrenergic antagonists (phentolamine and yohimbine) or a dopaminergic antagonist (haloperidol), but not with either a beta-adrenergic antagonist (propranolol) or a narcotic antagonist (naloxone). In addition, direct administration of dibutyryl cyclic-AMP into either the anterior hypothalamus, the nucleus accumbens or the caudate-putamen complex of rats produced the same behavioural responses as those produced by the intraventricular injection. Again, the behavioural responses induced by intracerebral injection of dibutyryl cyclic-AMP was antagonized by pretreatment with either alpha-adrenergic antagonists or a dopaminergic antagonist. The present data indicate that both the dopaminergic and the adrenergic receptors in the brain are involved in the behavioural excitation induced by dibutyryl cyclic-AMP and aminophylline in the rat.

Aminophylline↗

The pharmacological studies in central nervous system on the interaction of Taiwanese Veratri Formosani Rhizoma and Sophorae Radix.

The eighteen opposing drugs were to be recognized as absolute incompatibility of Chinese herbs. Ku-Shen (Sophorae Radix) opposed Li-Lu (Veratri Rhizoma) is one of these incompatible drugs. In this study, we attempted to investigate and identify the interactions of these two drugs in the CNS by means of modern pharmacological technics. The results elucidate that toxicity, number of retching movements, change of locomotor activity and the concentration of monoamines' metabolites of Li-Lu can be changed by Ku-Shen. From these results, further evidence was provided that the involvement of Li-Lu and Ku-Shen in the eighteen opposing drugs of Chinese ancient Pentsao are deemed to be significant.

Animals↗

The effect on gastrointestinal motility after ingestion of raw bile of grass carp (Ctenopharyngodon idellus) in the conscious rats.

The influence of raw grass carp bile on gastrointestinal motility was studied in conscious rats. It was found that the toxic bile prolonged the gastric emptying time, increased a marker substance traversed along the small intestine and accelerated the transit time along the colon. These findings might be explained by a very efficient protective response of the digestive system, and/or poisoning effect of the invading toxic substance in rats. Accumulation of fluid was found in the stomach, 20 min after ingestion of 0.3 ml of the toxic bile. Besides, ingestion of the raw bile also increased the urea nitrogen in blood, which may result from a loss of fluid volume through the gastrointestinal tract and (or) a direct action of the bile on the kidneys.

Animals↗

Involvement of both opiate and catecholaminergic receptors in the behavioural excitation provoked by thyrotropin-releasing hormone: comparisons with amphetamine.

Following direct administration of thyrotropin-releasing hormone (TRH), but not thyroid-stimulating hormone (TSH) or vehicle solution, into the lateral cerebral ventricle in rats, three main categories of behaviour were provoked: activity of the normal type--stimulation of forward locomotion, head and body rearing (as shown by an enhancement in gross movements); stereotyped activity--increased grooming and head swaying (as shown by an enhancement in fine movements); abnormal behaviour--tail elevation and piloerection (as observed grossly). The behavioural excitation caused by TRH was antagonized by pretreatment of the rats with either a narcotic receptor antagonist, naloxone, an alpha-adrenergic receptor antagonists, yohimbine, or a dopaminergic receptor antagonist, haloperidol, but not with a beta-adrenergic receptor antagonist, propranolol. Intraventricular administration of amphetamine to rats caused stimulation of forward locomotion, head and body rearing, increased grooming and sniffing. Unlike TRH, amphetamine did not produce wet-dog shakes, tail elevation and piloerection. Furthermore, the amphetamine-induced excitation was antagonized by pretreatment with a dopaminergic receptor antagonist, haloperidol, but not with either naloxone, yohimbine or propranolol. The data indicate that both opiate and catecholaminergic receptors are involved in the TRH-induced behavioural excitation, whereas dopaminergic receptors are involved in amphetamine-induced excitement in the rat.

Amphetamine↗