Changes in activity of some mechanisms of specific and nonspecific immunity in vitamin B1 deficiency

The effect of thiamine deficiency on the immune response and activity of certain mechanisms of natural immunity was studied in adult rats. Thiamine deficiency was simulated experimentally by a single injection of hydroxythiamine, a vitamin B₁ antagonist. Administration of hydroxythiamine caused a marked decrease in complement activity, phagocytic activity of the peripheral blood leukocytes, bactericidal activity of the serum, and antibody production in response to immunization with sheep's red blood cells. Conversely, lysozyme activity increased. In vitamin B₁ deficiency the intensity of incorporation of [¹⁴C]leucine into liver protein synthesis was reduced.Department of Pathological Physiology, N. I. Sechenov First Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR G. V. Vygodchikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 60–62, July, 1979.     

Relationships between Responsiveness of the Bronchi to Acetylcholine and Cyclic AMP Response of Lymphocytes to Beta1- and Beta2-Adrenergic Receptor Stimulation in Patients with Asthma

Decreased response of beta-adrenergic receptor has been considered to he one of the causes of increased responsiveness of the bronchi in asthma. Since beta-adrenergic receptor has two subtypes, beta₁ and beta₂, and the bronchodilating effect of beta stimulants is mediated by beta₂-receptor, responsiveness of the bronchi is expected to correlate to the cyclic AMP response of lymphocytes to a beta₂-stimulant. Responsiveness of the bronchi was expressed as respiratory threshold to acetylcholine (RT-Ach), which was the minimal concentration of acetylcholine solution to cause an initial decrease of FEV₁ of more than 20% of the baseline value. Beta₁ and heta₂-responses were expressed as the increments of cyclic AMP content of 10⁶ lymphocytes incubated with norepinephrine (beta₁-stimulant) and salbutamol (beta₂-stimulant).
RT-Ach showed a significant correlation with the beta₂-cyclic AMP response of lymphocytes, but not with the beta₁ -response among patients with asthma. Sixteen symptomatic patients on continuous beta-stimulants showed lower RT-Ach value and diminished beta₂-receptor activity of lymphocytes compared with 14 patients in remission. These results suggest that selective beta₂-adrenergic blockade may he one of the causes of bronchial hypersensitivity in asthma, though it should be noted that in this study beta-adrenergic responses were examined in lymphocytes and were compared with the responsiveneness of the bronchi. Possible beta-receptor subsensitivity induced by administration of beta-stimulants is discussed.     

荷人鼻咽癌裸鼠血浆MDA,cAMP／cGMP水平及PSP的影响

本实验利用ＢＡＬＢ／Ｃ裸小鼠，复制荷人鼻咽癌裸鼠模型，检测荷瘤鼠血浆丙二醛，ｃＡＭＰ，ｃＧＭＰ和ｃＡＭＰ／ｃＧＭＰ比值，观察云芝糖肽对荷人ＮＰＣ裸鼠的抑瘤作用及对荷瘤鼠血浆ＭＤＡ和ｃＡＭＰ／ｃＧＭＰ等的影响。结果发现荷瘤鼠血浆ＭＤＡ升高，ｃＡＭＰ，ｃＧＭＰ降低，ｃＡＭＰ／ｃＧＭＰ比值升高，高你低浓度ＰＳＰ对荷人ＮＰＣ裸鼠均有明显抗癌作用（Ｐ＜０．０１），抑瘤率５９．５８－９５．５３％；并可降低荷瘤     

Functional vulnerability of developing central nervous system to maternal thiamine deficiencies in the rat

Thiamine deficiency (B1 vitamin) was induced during three periods of rat central nervous system (CNS) ontogenesis. Females were fed a thiamine deficient diet such that developing offspring were exposed either to pre-, peri-, or postnatal thiamine deficiency. To control the effects of undernourishment generated by different thiamine deficiencies, every treatment group had its own pair-fed control pup from a non drug-treated but undernourished dam. Seven different developmental abilities (exploratory activity, emotional reaction, hind paws lifting reflex, wire grasping times, crawling and leap execution latencies, and nociception) were recorded in the offspring from the 10th to the 45th postnatal day. The vulnerability of developing brain to the specific lack of B1 vitamin increases from prenatal (28%) to perinatal (43%) and postnatal periods (57%).     

Pre‐conditioning activates adenosine utilization in a cost‐effective way during myocardial ischaemia

During pre‐conditioning the interstitial concentration of adenosine, in contrast to lactate, presents a die‐away curve‐pattern for every successive episode of ischaemia. This die‐away pattern might not necessarily be attributed to diminished adenosine production. The present study was undertaken to investigate whether pre‐conditioning alters the metabolic turnover of adenosine as observed by the lactate production during ischaemia. Interstitial levels of metabolites in pre‐conditioned (n=21) and non‐preconditioned (n=21) porcine hearts were monitored with microdialysis probes inserted in both ischaemic and non‐ischaemic tissue in an open chest heart model. Three subgroups perturbated with either plain microdialysis buffer (control), buffer containing adenosine (375 μM ), or buffer containing deoxyadenosine (375 μM ) were studied. All animals were subjected to 90 min of equilibrium microdialysis before 40 min of regional myocardial ischaemia and 120 min of reperfusion. Pre‐conditioning consisted of four repetitive episodes of 10 min of ischaemia and 20 min of reperfusion. Significantly higher levels of inosine and lactate were found in the ischaemic tissue of the pre‐conditioned subgroup receiving adenosine (P < 0.05) compared with the other two subgroups receiving deoxyadenosine and plain buffer, respectively. This difference was only valid for pre‐conditioned ischaemic myocardium, and hence equal amounts of inosine and lactate were produced in the non‐preconditioned ischaemic myocardium regardless of the presence of adenosine or deoxyadenosine. In the non‐ischaemic myocardium baseline levels of metabolites were measured in all subgroups. Pre‐conditioning favoured degradation of exogenous adenosine to inosine successively ending up in enhanced lactate production. This was probably because of the involvement of the hexose monophosphate pathway in the pre‐conditioned ischaemic myocardium. This route may therefore be supplementary in energy metabolism as a metabolic flow can be started by adenosine ending up in lactate without initial adenosine 5′‐triphosphate (ATP) investment. Utilization of adenosine in this way may also explain the successive die‐away pattern of adenosine seen in consecutive pre‐conditioning cycles.     

内生致冷原作用机制的研究

家兔侧脑室内注射纯化内生致冷原(endogenous cryogen,EC)引起直肠温度下降和耳皮肤温度上升,其反应与静脉注射的情况相似,但直肠温度降低更加迅速,所用剂量仅为静脉注射达到同样效应时的1/80。静脉注射EC降温反应过程中,体温下降至最低点时脑脊液cAMP浓度显著下降,而cGMP浓度没有显著改变,血浆cAMP和cGMP浓度均显著升高;体温回升至正常水平时脑脊液、血浆cAMP和cGMP浓度均与对照组无显著差异。本实验结果提示:(1)EC的主要作用部位可能是中枢神经系统;(2)cAMP可能参与EC降温反应的中枢机制。     

Fenoterol, a selective beta2-adrenergic agonist, and inhibition of IgE-mediated basophil histamine release

The present study was undertaken to evaluate the effect of fenoterol, a selective beta 2-adrenergic agonist, on basophil histamine release. Fenoterol at 10(-7) to 10(-3) M did not inhibit the release of histamine induced by Dermatophagoides farinae extract (D.f.) from leukocytes from allergic patients sensitive to mite. Similarly, there was no suppression of histamine release induced by anti-IgE and formyl-methionyl-leucyl-phenylalanine under the influence of fenoterol. Fenoterol caused a slight inhibition of the calcium ionophore A23187-induced histamine release at 10(-3) M with % inhibition of 11.8 +/- 2.4 (means +/- SEM, P less than 0.05). There was no synergism between fenoterol and theophylline in inhibiting D.f.-induced histamine release. Fenoterol did not suppress the release of histamine induced by antigen at low as well as high levels of release. Based on the data on the effect of fenoterol on IgE-mediated histamine release, it was concluded that in contrast to a human lung mast cell system, the beta-adrenergic receptor-adenylate cyclase system is not a control mechanism in IgE-mediated basophil histamine release.     

Atrial natriuretic factor (ANF) does not affect ion transport in human intestine but does in porcine intestine

The aim of this study was to test whether atrial natriuretic factor (ANF) exerts any effect on human intestinal ion transport, and the porcine intestine was used as a positive control of ANF's effects. Tissues from human proximal (n = 6) and distal (n = 6) colons, and from distal ileum (n = 6) were mounted in Ussing chambers, and short circuit current (I_sc) was measured subsequent to serosal application of ANF (10^--⁶ m), 8–Br-cyclic guanosine monophosphate (8–Br-cGMP) (10^--⁴ m), and theophylline (10^--² m). ANF did not affect I_sc whereas 8–Br-cGMP increased I_sc by 28 (8–53), 16 (3–36), and 16 (5–41) μA cm^-2 in the distal colon (DC), proximal colon (PC) and distal ileum (DI), respectively. Likewise, transepithelial potential difference (PD) became more negative by 5.0 (0.6–8.9), 2.5 (0.4–4.0) and 0.9 (0.3–2.3) mV in DC, PC, and DI, respectively, subsequent to addition of 8–Br-cGMP. I_sc and PD were further increased by theophylline. Additional radio-isotope flux studies in human colon revealed that ANF did not affect electroneutral sodium and chloride transport either. For comparison, ANF (10^--⁶ m) was administered to large intestinal tissues from young pigs in which ANF induced a significant increase in I_sc which was comparable to the 8–Br-cGMP response in humans. The porcine I_sc response was partly inhibited by chloride-free solution on the serosal side, by serosal application of bumetanide (10^--⁴ m) and BaCl₂ (10^--³ m), and mucosal application of the chloride-channel blocker diphenylamine-2–carboxylate (DPC) (10^--³ m). Mucosal amiloride (10^--⁵ m) pre-treatment reduced baseline I_sc but did not affect the porcine intestinal I_sc response to ANF. In vitro radio-autography demonstrated specific binding sites for ANF in porcine distal colon, whereas no apparent labelling was observed in human distal colon. These findings suggest that the lack of effect of ANF on sodium and chloride transport in human distal ileum and colon is probably due to lack of ANF receptors. In the porcine intestine, however, the I_S0 response induced by ANF seems to involve stimulation of electrogenic chloride secretion, whereas electrogenic sodium absorption seems unaffected.     

Effect of atrial natriuretic factor and cyclic guanosine monophosphate on water and urea transport in the inner medullary collecting duct

We examined the action of high (2×10^–8M) and low (6×10^–9M) concentrations of atrial natriuretic factor (ANF) on water and urea transport in the rat inner medullary collecting duct (IMCD) using the in vitro microperfusion technique. We measured the hydraulic conductivity (Lp ×10^–6 cm/atm per second) and both lumen-to-bath (P _u(lb)) and bath-to-lumen (P _u(bl)) ¹⁴C-urea permeabilities (P _u× 10^–5 cm/s) in the absence and in the presence of vasopressin (VP). High concentrations of ANF were able to inhibit the maximum activity of (50 U/ml) VP-stimulated L _p but physiological concentration of ANF inhibit only submaximum activity (10 U/ml) of VP-stimulated L _p. The hydrosmotic effect of dibutyryl-cyclic 3,5 adenosine monophosphate (cAMP) (10^–4M) was unchanged by high concentrations of ANF (2×10^–8M). Also we found that high (10^–4M) and low (10^–6M) concentrations of exogenous cyclic 3,5-guanosine monophosphate (GMP) while unable to change the Lp in the absence of VP, decreased the maximum activity of VP-stimulated Lp significantly. We also found that ANF inhibits partially and in a reversible manner the VP-stimulated P _u(lb) but not the VP-stimulated P _u(bl). These results demonstrated that plasma concentrations of ANF observed during volume expansion (10^–10M) are able to inhibit submaximum activity of VP-stimulated (10 U/ml) L _p in the rat IMCD, this effect seems to occur before cAMP formation and it appears to be mediated by cGMP. ANF (6× 10^–9M) also reduced the VP-stimulated urea outflux. Therefore, the increase in water excretion produced by ANF could be explained, at least in part, by the inhibition by ANF of vasopressin effects on water and urea transport in the IMCD.This study was presented in part at the VI Latin American Congress of Nephrology, Brazil, October 1985 and at the X^th International Congress of Nephrology, London, July 1987.     

实验性过敏性哮喘豚鼠外周血液淋巴细胞β肾上腺素能受体系统的变化

在建立外周血液淋巴细胞β受体测定法的基础上,动态地观察了实验性过敏性哮喘豚鼠外周血液淋巴细胞中β受体最大结合容量(Bmax)、cAMP含量,以及血浆中儿茶酚胺(CA)含量的变化,发现它们都呈明显的时相性改变。通过分析它们发生的时间过程和相互关系,认为:在过敏性哮喘时所观察到的淋巴细胞β受体Bmax值的降低,乃是高水平内源性儿茶酚胺所致受体失敏的结果;并对所观察到的变化的意义作了初步探讨。