白蛋白微球作为肝靶向给药载体的研究

用均匀设计方法和计算机技术筛选了乳化化学交联法制备白蛋白微球的六个因素,十二个水平。优化出最佳制备工艺,制备了平均粒径0.41～0.47μm的白蛋白微球。将此工艺制备的¹²⁵I-白蛋白微球做动物体内研究,结果表明微球iv后主要浓集在肝脏,可达注入总剂量的68%,此微球在靶组织肝脏的变化规律可用二室模型契合。     

Effect of poly rI:rC treatment upon the metabolism of [14C]-paracetamol in the BALB/cJ mouse

The effect of the immunomodulator, poly rI:rC, upon the in vivo metabolism of [14C]-paracetamol has been investigated in male BALB/cJ mice. In both poly rI:rC treated and control groups of mice the major part of the dose was excreted in the 0-24 hr urine and the major urinary metabolites were the glucuronic acid and sulphate conjugates. The urinary excretion of these two conjugates and of free paracetamol was not significantly altered following poly rI:rC treatment. Following enzymic hydrolysis of glucuronides and sulphates, the 3-cysteine, 3-mercapturate, 3-thiomethyl and 3-methylsulphoxide metabolites of paracetamol were all identified in the 0-24 hr urine together with very small amounts of 3-methoxy paracetamol. Although poly rI:rC treatment reduced the proportional urinary excretion of each of the thio adducts the individual differences were not significant. However, total thio adduct excretion, an indirect estimate of the metabolic activation of paracetamol, was significantly lower following poly rI:rC treatment. This depression in the urinary excretion of thio adducts following poly rI:rC treatment is discussed in relation to possible implications for paracetamol toxicity.     

Further study on the vascular basis for the reimplantation of the hand amputated through the palm

Summary Based on the anatomic data obtained from earlier studies on the vascular anatomy of the hand, the vascular architecture in the palm of the hand was studied on 60 sides of unembalmed adult upper extremities. Each palm was divided into 64 squares by 8 sagittal and 8 transverse sections. The vascular architecture in these squares and the arterial relations between them were observed and measured by angiography, operative microscopic dissection and computerised three-dimensional reconstruction. According to the pattern of the blood-vessels, the amputated palms can be classified into 4 types. The anatomic basis for the vascular anastomosis in each type is defined. There are three key-areas for the blood-supply of the palm and their significance is discussed. Apart from the 4 types of transversely amputated palms, the repair programe of the blood-vessles in 4 types of common obliquely amputated palms are also discussed.

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Etude complémentaire de l'anatomie vasculaire de la main pour la réimplantation des amputations transpalmaires

Résumé Sur la base de données anatomiques obtenues lors de précédents travaux sur l'anatomie vasculaire de la main, l'architecture vasculaire palmaire a été étudiée sur 60 extrémités supérieures de cadavres d'adultes, non embaumés. Chaque paume a été divisée en 64 carrés par 8 sections sagittales et 8 sections transversales. L'architecture vasculaire à l'intérieur des carrés et les relations artérielles entre eux ont été étudiées et mesurées par angiographie, dissection au microscope opérateur et reconstruction computérisée en 3D. Les paumes amputées ont été regroupées en 4 types d'après la distribution des vaisseaux sanguins. Les données anatomiques concernant les anastomoses vasculaires sont précisées. Il existe trois zones clés pour l'irrigation de la paume. Leur importance quant à l'irrigation de la main est exposée. Outre la division des paumes amputées transversalement en 4 types, le programme de réparation de vaisseaux dans les 4 types d'amputations obliques communes de la paume et aussi discuté.

     

Inhibition of ω-conotoxin-sensitive Ca2+ channel currents by internal Mg2+ in cultured rat cerebellar granule neurones

The effects of changing the intracellular concentrations of either free Mg²⁺ ions ([Mg²⁺]_i) or Mg²⁺-bound adenosine triphosphate ([Mg · ATP]_i) on Ca²⁺ channel currents were assessed in cultured rat cerebellar granule neurones using the whole-cell patch-clamp technique. Raising [Mg²⁺]_i from 0.06 mM to 1.0 mM inhibited Ca²⁺ channel currents by approximately 50%. The action of -conotoxin GVIA (-CgTX), a selective inhibitor of N-type Ca²⁺ channels was also investigated. With increasing [Mg²⁺]_i, the proportion of current irreversibly blocked by -CgTX was reduced, and was negligible (approximately 5 pA of current) in the presence of [Mg²⁺]_i values of 0.5 mM or greater. Block of the -CgTX-sensitive current accounted for the reduction in total current by concentrations of [Mg²⁺]_i to 0.5 mM. Raising [Mg²⁺]_i had no effect on the rate of decay of Ca²⁺ currents, but did produce a negative shift in current activation, possibly due to a non-specific interaction with negative surface charge. Altering [Mg · ATP]_i from 0.3 to 5.0 mM caused a twofold increase in the size of currents without affecting the proportion of current sensitive to -CgTX. [Mg²⁺]_i was also effective in inhibiting the Ca²⁺ channel current following potentiation by increasing [Mg · ATP]_i. These data suggest that -CgTX-sensitive current in these cells is selectively inhibited by internal Mg²⁺ whereas both -CgTX-sensitive and -resistant components of current are potentiated by internal Mg · ATP. The mechanism by which Mg²⁺ inhibits N-type channels is unclear, but may involve an open channel block.     

Modulation of neuronal T-type calcium channel currents by photoactivation of intracellular guanosine 5'-O(3-thio) triphosphate

Low voltage-activated T-type Ca2+ channel currents were recorded from cultured rat dorsal root ganglion neurons using the whole-cell clamp technique with Ba2+ as the charge carrier. The T-type Ca2+ channel current was identified by its low threshold of activation (Vc -50 to -20 mV from VH - 90 mV), its kinetics of inactivation and its sensitivity to NiCl2 (100 microM). It was also sensitive to 1-octanol (1 microM). omega-Conotoxin (1 microM) markedly reduced the high threshold voltage-activated Ca2+ channel currents but did not inhibit the T-type Ca2+ channel current. Photorelease of intracellular guanosine 5'-O(3-thio) triphosphate from a photolabile "caged" precursor had dose-dependent effects on the T-type Ca2+ channel current. At a concentration of 6 microM, guanosine 5'-O(3-thio) triphosphate enhanced the current, but further photorelease of guanosine 5'-O(3-thio) triphosphate (up to 20 microM) inhibited the current. Only the inhibitory response was sensitive to pertussis toxin. These data suggest that more than one G-protein is involved in T-type Ca2+ channel current modulation. Inclusion of guanosine 5'-O(2-thio) diphosphate (1 mM) in the patch solution prevented guanosine 5'-O(3-thio) triphosphate from potentiating the current, and greatly attenuated the inhibitory effects observed when larger amounts of guanosine 5'-O(3-thio) triphosphate were photoreleased. Photorelease of guanosine 5'-O(2-thio) diphosphate had no effect on T-type current but did significantly increase the high voltage-activated current. A low concentration of (-)-baclofen (2 microM), potentiated T-type current, while 100 microM(-)-baclofen inhibited T-type current.     

Myocardial disease and catecholamine metabolism in JCR:LA-corpulent rat

The JCR:LA-cp rat is a strain carrying the mutant cp (corpulent) gene. Animals that are homozygous cp are hyperphagous, hyperinsulinemic, hyperlipidemic, and obese. Corpulent male rats, but not females or lean rats, develop atherosclerotic lesions and myocardial lesions. Since the myocardial lesions are apparently of ischemic origin, the noradrenergic system and vascular hyperactivity and vasospasm may play a role in the pathogenesis. To test this we have studied the brain contents of the amines norepinephrine, dopamine, and 5-hydroxtryptamine and their breakdown products and depleted the peripheral sympathetic terminals with 6-hydroxydopamine. Only 5-hydroxytryptamine and 5 hydroxyindole-3-acetic acid were present at higher concentrations in the corpulent rats with depressed levels of dopamine in very young or old lean rats. The activity of monoamine oxidase may provide an indication of nonadrenergic activity in tissue. The activity in the heart increased with age and was higher in the corpulent rats than in the lean at all ages. Activity in aorta was independent of age or genotype. Long term treatment with 6-hydroxydopamine caused marked depletion of norepinephrine in the heart with only a slight decrease in brain concentration. There were no effects on the hyperlipidemia or hyperinsulinemia that are strongly associated with vascular and myocardial disease. The myocardial lesion frequency in corpulent rats was not altered by the chemical sympathectomy. The results suggest that norepinephrine and the sympathetic nervous system are probably not involved in the generation of the myocardial lesions or metabolic abnormalities in this strain of rat.     

The locus of control: It’s significance in the irritable bowel syndrome

PSYCHOLOGICAL factors have a role in Irritable Bowel Syndrome symptomatology. The locus of control test determines an individual’s degree of internality or externality. The degree of internality or externality does not influence the site of major Irritable Bowel Syndrome symptomatology. Externalizers have a worse prognosis than internalizers. This effect on prognosis should be borne in mind when testing for diet and or drug efficacy.     

Adolescents׳ perceptions of peers with depression: An attributional analysis

Understanding adolescents? perceptions of peers with depression is vital in order to tackle peer exclusion and lessen stigmatization. To examine adolescents? perceptions of a hypothetical peer with depression, we test an attributional model: that stigma towards persons with mental disorders is influenced by attributions about the causes of their disorders and inferences of personal responsibility. Participants were 401 adolescents from 4th year/10th grade with an age range of 14.75–17.08 years (M=15.90 years; S.D.=0.403 years). Structural Equation Modeling was employed to assess the relationships among causal attributions (personal control), perceived responsibility, and emotional reactions, in predicting social acceptance/exclusion of a peer with depression. Results indicated that (a) if the peer with depression is perceived as having little control over the cause of depression, responsibility is not inferred, participants feel sympathy and pity, and are likely to socially accept the peer (b) gender of vignette character and participant influence these responses. This study builds on our theoretical understanding of why adolescents with depression may face social exclusion from peers by applying a well‐established theory in social psychology. Findings should be incorporated into the design of interventions aimed at reducing peer exclusion and stigmatization of adolescents with depression.