加强生物教学中的科学方法训练

在生物教学中科学方法训练是能力培养的基础，是完成生物学教学目的的途径之一。因此，在生物学中加强科学方法训练，使学生了解科学探究的基本过程，掌握基本的科学研究方式。     

Effects of phospholipase A2 from cobra and bee venom on the presynaptic membrane

L. G. Magazanik, I. M. Gotgilf, T. I. Slavnova, A. I. Miroshnikov and U. R. Apsalon. Effects of phospholipase A₂ from cobra and bee venom on the presynaptic membrane. Toxicon17, 477–488, 1979.—Phospholipases A₂ from bee venom and cobra venom have been isolated and studied. A parallelism was found between enzymatic activity and the ability to block spontaneous miniature end-plate potentials (m.e.p.p.'s) or end-plate potentials (e.p.p.'s) induced by nerve stimulation in the frog sartorius muscle. Different experimental procedures affected both enzymatic activity and blocking ability in qualitatively the same way. Thus, modification of the histidine residue in cobra venom phospholipase by bromophenacyl bromide or the removal of Ca-ions from the medium abolished both activities. Replacement of Ca²⁺ by Sr²⁺ inhibited both the enzymatic and presynaptic effects of cobra venom phospholipase, but did not inhibit the presynaptic action of bee venom phospholipase and decreased its enzymatic activity only 6-fold. Irreversible binding of cobra and bee venom phospholipase to the presynaptic membrane was found in Ca-free solution but Ca-ions were essential for the presynaptic blocking effect induced by these phospholipases. A reduction in the effect of high K⁺ on m.e.p.p. frequency was observed after cobra venom phospholipase treatment. The similar effects of hypertonic sucrose solution and the mitochondrial poison TTFB (4,5,6,7-tetrachloro-2-trifluoromethylbenzimidazole) were changed only slightly by bee and cobra venom phospholipase pretreatment. It is concluded that the mechanism of presynaptic blockade induced by bee venom and cobra venom phospholipase consists mainly of damage to sites of release at the presynaptic membrane. There are also some signs of disturbances of depolarization-secretion coupling and of the process of formation of new quanta. The possible functional role of enzymatic activity in the presynaptic effect is discussed.     

Factors influencing the transfer of xanthines across the everted rat jejunum

A number of factors having the potential to influence the transfer of theophylline across the everted rat jejunum were examined. The transfer of several other xanthine derivatives was also investigated. Strophanthin-K and 2,4-dinitrophenol had no effect on theophylline transfer. The transfer of theophylline from a 2:1 complex with phenobarbital was identical to that of theophylline alone. Magnesium ion (120 mM) and hypertonicity (600 mOsm) had no effect on the transfer of theophylline at pH 5.5. With the exception of xanthine, the clearance of all of the xanthine homologs tested was related to their partition coefficients in a chloroform/pH 7.4 phosphate buffer.     

Effect of the inhalation of zinc and dietary zinc on paraquat toxicity in the rat.

A possible pharmacological effect of zinc against the pulmonary toxicant paraquat has been studied. Rats were treated with zinc either by inhalation of zinc oxide fume aerosol or consumption of zinc supplemented food. The animals were then injected with paraquat ip (30 mg/kg) and lethality monitored for 7 days. Neither zinc inhalation nor dietary zinc protected the animals against paraquat-induced lethality. In fact, exposure of rats to zinc oxide fume aerosol potentiated the lethal effects of paraquat. The mechanism of paraquat-induced lung toxicity at the cellular level does not appear to directly involve a zinc-dependent step. This distinguishes paraquat from other injurious agents which have been reported to respond to zinc.     

A possible mechanism of the antiarrhythmic action of glucagon

The effects of glucagon on ouabain-induced ventricular arrhythmias were studied in dogs with normal cardiac conduction systems and in dogs with surgically induced complete heart block. Glucagon, 20 μg/kg, effected conversion to a sinus rhythm in eight of nine animals with normal conduction systems, and in each instance the conversion occurred with a sinus tachycardia whose rate exceeded the rate of pre-existing ventricular arrhythmia. The one animal which failed to convert to a sinus rythm did not develop a sinus nodal rate faster than the rate of the ventricular arrhythmia. In 10 animals with ouabain-induced ventricular arrhythmias atrial pacing was employed to overdrive the arrhythmia, and in 6 cases this was successful. In all 6 experiments subsequent administration of glucagon after pacing resulted in conversion to a sinus rhythm at a rate greater than the minimum atrial pacing rate required to effect capture of the ventricules. In 4 of the 10 animals neither atrial overdrive nor glucagon were successful in effecting sinus conversion, but ventricular rate was slowed by lidocaine. In addition, in 5 animals with complete heart block and ouabain-induced ventricular tachycardia which were given glucagon, 20 μg/kg, there was no change in the tachycardia and no change in the ECG pattern associated with the arrhythmia. It was concluded that the antiarrhytmic action of glucagon in this arrhythmia is mediated through a supraventricular action to elevate sinus rate above that of the dominant ventricular focus and thus allow a return to dominance of the sinus node.     

Studies on the nature of the in vitro enhancement of biphenyl 2-hydroxylation provoked by some chemical carcinogens

Studies on the metabolism of [¹⁴C]biphenyl and of 2-hydroxy and 4-hydroxybiphenyls confirm that preincubation of fresh hepatic microsomal preparations from rats or hamsters with chemical carcinogens such as safrole, benz[a]pyrene and 2-acetamidofluorene and a NADPH regenerating system produces an increase in the levels of 2-hydroxybiphenyl, through a specific increase in its formation from biphenyl. These data also support the validity of the fluorimetric assay method for monitoring this reaction. The addition of oestradiol or glutathione to the incubation mixture and the use of various preincubations and time periods with the carcinogens and NADPH prior to adding biphenyl indicate that production of an active metabolite of the carcinogens is probably a pre-requisite for the in vitro enhancement of biphenyl 2-hydroxylase to occur.The lack of effectiveness of EDTA in enhancing biphenyl 2-hydroxylase and the complete destruction of this enhancement by short-term storage of microsomal preparations at -20° suggests that the phenomenon is different from that of degranulation of the endoplasmic reticulum by carcinogens.     

邻苯二甲酸二丁酯对大鼠睾丸毒性的研究 Ⅰ.形态学变化及时间-效应关系

本研究对饲喂DBP20,000ppm10、20及30天大鼠睾丸的损伤部位及时间关系,首次进行了观察。结果表明,饲喂DBP20天,大鼠睾丸曲细精管严重萎缩,生精细胞变性、脱落,附睾尾精子计数及活动与不活动精子比值下降,支持细胞的多种细胞器变性。     

Synergism of the toxicity of physostigmine and neostigmine by lithium or by a reserpine-like agent (Ro4-1284)

A single sublethal i.p. dose of lithium chloride (300 mg/kg or 7.1 meq/kg) followed 12 h later by an otherwise sublethal s.c. dose of physostigmine sulfate (1.0 mg/kg) resulted in 90% mortality among male rats following a pronounced cholinergic syndrome, including convulsions. This confirms a previous report of a lethal synergism of physostigmine after subacute dosing with lithium. Mortality could be completely prevented by 1.0 mg/kg of atropine sulfate given 30 min before physostigmine, but was incompletely, if at all, reduced by selective peripheral cholinergic blockers, methylatropine bromide (0.5, 1.5 mg/kg) or glycopyrrolate (1 mg/kg). This suggested a predominantly central site for the toxic interaction. However, a similar synergism of lethality caused by neostigmine methylsulfate (0.3 mg/kg, s.c.) after treatment with lithium, which could be eliminated by methylatropine or glycopyrrolate, indicates that lithium may also produce lethal synergism of a cholinesterase (ChE) inhibitor that does not act centrally. Ro4-1284, an agent that has reserpine-like actions, was tested in combination with physostigmine or neostigmine; it showed synergism of toxicity nearly the same as in the case of lithium plus the cholinergic agents. These findings support the hypothesis that lithium causes the toxic synergism via a reduction of adrenergic activity, leading to an imbalance between adrenergic and cholinergic influences and a consequent failure to tolerate the effects of the ChE inhibitors. A potential hazard for the clinical use of physostigmine and neostigmine, concurrently with lithium or reserpine-like agents, it suggested.     

Calcium and 1-hydroxyethylidene-1,1-bisphosphonic acid: polynuclear complex formation in the physiological range of pH

1-Hydroxyethylidene-1,1-bisphosphonic acid (HEDP) is used in a variety of diagnostic, research and therapeutic applications at in vivo concentrations of from < 1 μ M to > 1 mM. Previous studies have shown that calcium and HEDP form polynuclear aggregate complexes at high pH. Calcium ion titrations at constant pH 8.0, and pH titrations at 1:1 and 2:1 ratios of total calcium to total diphosphonate, provide evidence for the occurrence of aggregation of calcium and HEDP under physiological conditions. A robust feature of several polynuclear models examined is a dramatic pH dependence of polynuclear species concentrations between pH 5.5 and 7.0.     

Impaired drug metabolism in experimental cirrhosis in the rat

Cirrhosis was produced in the rat by chronic administration of phenobarbital and carbon tetrachloride for 10 weeks. The metabolism of three substrates, aminopyrine. hexobarbital and propranolol, has been investigated in a 9000 g supernatant fraction of liver homogenate and in intact hepatocytes in cirrhotic livers and compared to appropriate phenobarbital-treated controls. In the 9000 g supernatant preparation, the maximal velocity of metabolism for each substrate and the cytochrome P450 concentration were reduced significantly in cirrhotic livers, while total protein and DNA concentration remained unchanged. In intact hepatocytes, the V_maxfor each substrate was reduced, while the apparent K_m remained unchanged. In both in vitro systems, the metabolism of propranolol and of hexobarbital was influenced by cirrhosis to a greater extent than that of aminopyrine. It is concluded that the carbon tetrachloride-phenobarbital model of cirrhosis in the rat is a suitable model in which to study the effects of chronic liver disease on drug disposition.     

Examination of the itch response from the raphides of the fishtail palm Caryota mitis.

The raphides in the mature fruit of the fishtail palm Caryota mitis Lour. were isolated by mechanical separation. These were shown by X-ray crystal analysis to be calcium oxalate monohydrate (Whewellite). The application of an aqueous suspension of the raphides to intact human skin results in an immediate, severe itch sensation. An investigation of this phenomenon appears to indicate that this is due solely to a mechanical action of the calcium oxalate needle and not to the previously postulated action of organic toxins or enzymes introduced through the skin by the penetrating action of the raphides.     

Effects of triethylenetetramine upon the metabolism and toxicity of 63NiCl2 in rats

Triethylenetetramine (TETA, 0.75 mmol/kg, im) was administered to Fischer rats immediately prior to ⁶³NiCl₂ (0.068 or 0.10 mmol/kg, ip or im) to determine (a) effects of TETA upon ⁶³Ni-kinetics, and (b) antidotal effects of TETA upon Ni-induced nephrotoxicity and hyperglycemia. TETA markedly reduced plasma ⁶³Ni concentrations and greatly increased urine ⁶³Ni excretion during 6 hr after injection of ⁶³NiCl₂, compared to values in control rats that received only ⁶³NiCl₂. In rats killed 6 hr after injections of TETA and ⁶³NiCl₂, ⁶³Ni concentrations in liver, kidney, spleen, lung, and heart averaged 3.4, 0.72, 0.27, 0.22, and 0.12 times corresponding ⁶³Ni concentrations in organs from control rats that received only ⁶³NiCl₂. The results supported the hypothesis that combined administration of TETA and ⁶³NiCl₂ resulted in partition of the body pool of ⁶³Ni between two major ⁶³Ni-components: (a) ⁶³Ni-TETA complex, and (b) nonchelated-⁶³Ni, and that each ⁶³Ni-component was eliminated from plasma according to its respective clearance. The renal clearance of ⁶³Ni-TETA complex was estimated to be >20 times that of nonchelated-⁶³Ni. Administration of TETA substantially reduced Ni-induced proteinuria and aminoaciduria. TETA did not prevent Ni-induced hyperglycemia and hyperglucagonemia, but TETA did partially inhibit Ni-induced hyperinsulinemia.     

On the intestinal transit of a single non-disintegrating object

A method is described for the measurement of the rate of transit of a non-disintegrating object through the gastrointestinal tract of human subjects using a gamma camera. A three-dimensional co-ordinate for the object is obtained by reference to external markers placed on the front and side of the body. Passage through the duodenum was very rapid and the rate of transit could not be measured. Thereafter the mean transit rate through the small intestine was measured at 4.2–5.6 cm · min ⁻¹ and was reasonably consistent between subjects. This is in contrast to the time for the object to leave the stomach which varied from 15 to 197 min.     

Chemical and biochemical characteristics of O-demethylation of chlorotrianisene in the rat

The effects of NADPH concentration and of two inhibitors of the microsomal mixed function oxidase system [2-diethylaminoethyl-2,2-diphenyl valerate hydrochloride (SKF 525-A) and metyrapone] on rat liver microsomal O-demethylation of the triphenylethylene estrogen chlorotrianisene (CTA) were studied. Comparative data were obtained using untreated and phenobarbital-pretreated rats of both sexes. In the presence of microsomes from males, O-demethylation was induced slightly by phenobarbital (PB), and it was inhibited substantially by SKF 525-A, particularly with uninduced microsomes. Metyrapone had little inhibitory effect. In the presence of microsomes from females, O-demethylation was neither induced by PB nor inhibited significantly by SKF 525-A or metyrapone. Incubation of CTA with male rat microsomes afforded, after purification, a mixture of monophenolic metabolites which consisted primarily of a 1:1 mixture of E- and Z-desmethylchlorotrianisene (DMCTA).     

Acute tobacco smoke exposure alters the profile of metabolites produced from benzo[a]pyrene by the isolated perfused rabbit lung

The influence of whole tobacco smoke or the gas phase from smoke on the metabolism of $\text{[}{}^{14}\text{C]benzo}\text{[a]}\text{pyrene}$ was e xamined using the isolated perfused rabbit lung model. Fresh whole tobacco smoke mixed with the air ventilating the perfused lung produces an immediate and dose related decrease in the metabolism of $\text{[}{}^{14}\text{C]benzo}\text{[a]}\text{pyrene}$. The metabolites of $\text{[}{}^{14}\text{C]benzo}\text{[a]}\text{pyrene}$, diols, quinones, phenols and polar compounds are generally decreased in quantity. At the lowest level of smoke administered the percentage of BP-7,8-diol produced is increased dramatically. The results indicate that one of the factors contributing to the carcinogenicity of tobacco smoke may be its ability to produce an immediate alteration in the pulmonary metabolism of polycyclic aromatic hydrocarbons.     

The mechanism of the effect of acute stress on hexobarbital metabolism

The effect of acute stress (unilateral hind-leg ligation for 1 hr) on hepatic metabolism of hexobarbital (HB) was studied in the rat. A stress duration-response relationship was found for stress inhibition of HB metabolism. The hepatic microsomal protein content was not affected, but the hepatic microsomal cytochrome P-450 content was reduced approximately 45% by this stress treatment. Stress caused a twofold increase in plasma corticosterone level and had no effect on plasma corticosterone level of adrenalectomized rats. Hexobarbital metabolism was not affected by stress in adrenalectomized rats. Thus, the inhibition of hepatic HB metabolism by acute stress may be caused by the increased release of corticosterone induced by acute stress.     

A Monte-Carlo model for the passive diffusion of drugs through the stratum corneum

The diffusion of solute molecules through the stratum corneum has been described using a Monte-Carlo random walk model. The results obtained are in agreement with the solutions obtained from Fick's first and second laws. The method is computationally simple to apply, can handle time variation of the stratum corneum's thickness and diffusion coefficient, and provides physical insight into the process of diffusion on a molecular level.     

Influence of rat brain superoxide dismutase inhibition by diethyldithiocarbamate upon the rate of development of central nervous system oxygen toxicity

Exposure to oxygen at pressures greater than 2.8 ATA (OHP) results in central nervous system toxicity seen as grand mal seizures. The time to onset of seizures (ts) is related to the pO2 above the 2.8 ATA threshold. The components of the endogenous antioxidant defense mechanism, superoxide dismutase (SOD), glutathione measured here as nonprotein sulfhydryl content (NPSH), glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GR), and glutathione peroxidase (GPx) occur in brain. Their role in OHP-induced CNS toxicity is not clear. This study examined the effect of inhibition of SOD by diethyldithiocarbamate (DDC) on ts at 4 ATA O2. Antioxidant components (SOD, NPSH, G-6-PD, GR, and GPx) were measured in male Sprague-Dawley rats pretreated with 250, 500, and 1000 mg/kg DDC ip, 2 hr prior to termination in room air. SOD activity was inhibited 11, 31, and 49%, respectively, when compared with control values. Among the other antioxidant components, only GPx showed a significant loss of activity of 24% at 1000 mg/kg DDC. Rats were also pretreated 2 hr prior to exposure to hyperbaric oxygen with either 250, 500, or 1000 mg/kg DDC. Ts for the treated animals was significantly shortened by 12, 55, and 75%, respectively, compared to the saline-treated, oxygen-exposed control animals. These studies demonstrated that the rate of onset of CNS oxygen toxicity was increased by inhibition of SOD by DDC. These data suggested that SOD plays a role as part of an endogenous antioxidant defense mechanism in the brain.