Analysis of the inotropic action of ouabain in rat ventricles: two apparent ouabain inotropic responses

Two distinct inotropic effects of ouabain were observed in 68 of 82 right ventricular strips of rats with ED50s of 0.5 and 20 microM referred to as "low-dose" and "high-dose" effects, respectively. The other 14 strips showed monophasic dose-response curves, with an apparent ED50 of 0.3 microM; the inotropic response to ouabain or isoproterenol developed by these atypical strips did not exceed 50% over control. In the strips showing the biphasic inotropic response curves, the proportion of the "low-dose" effect varied from 6 to 89% of the maximum response. After treatment with 160 microM ouabain, followed by 60 min of washout, the maximum developed tension in response to ouabain was unchanged, but the "low-dose" effect was abolished or dramatically reduced. In those cases with a remaining "low-dose" response, the response was only 12% or less of the maximum and the ED50 was shifted from 0.3 to about 3 microM ouabain by the washout. The atypical strips, which showed only the "low-dose" effects during the first ouabain exposure, revealed after washout a consistent "high-dose" effect with an ED50 of about 12 microM ouabain. The data show that the two inotropic responses exist in all ventricular strips and that in some strips, after ouabain washout, a residue of the "low-dose" effect remains.     

Behavioural evidence that magnetic field effects in the land snail,Cepaea nemoralis,might not depend on magnetite or induced electric currents

Although extremely low frequency (ELF) magnetic fields (<300 Hz) appear to exert a variety of biological effects, the magnetic field sensing/transduction mechanism(s) remains to be established. Here, using the inhibitory effects of magnetic fields on endogenous opioid peptide-mediated “analgaesic” response of the land snail. Cepaea nemoralis, we addressed the mechanism(s) of action of ELF magnetic fields. Indirect mechanisms involving both induced electric fields and direct magnetic field detection mechanisms (e.g., magnetite, parametric resonance) were evaluated. Snails were exposed to a static magnetic field (B_DC=78±1 μT) and to a 60 Hz magnetic field (B_AC=299±1 μT peak) with the angle between the static and 60 Hz magnetic fields varied in eight steps between 0° and 90°. At 0° and 90°, the magnetic field reduced opioid-induced analgaesia by approximately 20%, and this inhibition was increased to a maximum of 50% when the angle was between 50° and 70°. Because B_AC was fixed in amplitude, direction, and frequency, any induced electric currents would be constant independent of the B_AC/B_DC angle. Also, an energy transduction mechanism involving magnetite should show greatest sensitivity at 90°. Therefore, the energy transduction mechanism probably does not involve induced electric currents or magnetite. Rather, our results suggest a direct magnetic field detection mechanism consistent with the parametric resonance model proposed by Lednev. © 1996 Wiley-Liss, Inc.     

Reconstituted human breast milk PCBs as potent inducers of aryl hydrocarbon hydroxylase

The major polychlorinated biphenyl (PCB) components identified in human breast milk have been synthesized and a reconstituted breast milk PCB mixture representing the average levels determined in the Osaka Prefecture in Japan has been prepared. The dose effecting the half-maximal (ED₅₀) induction of rat hepatic microsomal aryl hydrocarbon hydroxylase (AHH) for the reconstituted breast milk PCBs (ED₅₀ ～12 μmol·kg^?1) was approximately seven times less than the ED₅₀ for the commercial PCB mixture, Kanechlor 500. The increased biological potency of the former mixture reflects the preferential bioconcentration of the toxic PCB congeners, 2,3,3′,4,4′-penta-, 2,3′,4,4′,5-penta- and 2,3,3′,4,4′,5-hexachlorobiphenyl.     

Stimulation-evoked release of purines from the rabbit retina

The evoked release of purines from rabbit retinae preloaded with [³H]adenosine was studied in vitro. Potassium (8.6–43.6 mM) and ouabain (1 or 10 μM) increased the release of radioactivity in a concentration-dependent manner. The K⁺-evoked release was significantly reduced when the superfusion was carried out at 2–4°C. The effect of K⁺ (8.6, 13.6 and 23.6 mM) and of ouabain (1 μM) were completely abolished when the retinae were superfused with a Ca²⁺-free medium containing 0.1 mM EGTA. Calcium removal only partially reduced the effect of higher K⁺ and ouabain concentrations (43.6 mM and 10 μM, respectively). Further, the effect of K⁺ was found to be independent of extracellular Ca²⁺ when retinae were pretreated with ouabain for 30 min. Stimulation of the retina with light flashes induced a small, persistent increase in the release of radioactivity observable for several minutes after the end of stimulation.The superfusate contained mainly hypoxanthine and inosine. There were no significant changes in the relative proportions of the different purine compounds released before or in response to either K⁺ (23.6 mM) or ouabain (10 μM) stimulation. Potassium stimulation significantly increased the release of adenosine, inosine and hypoxanthine. Addition of the adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), significantly increased the relative proportions of released endogenous adenosine and inosine.The results indicate that K⁺ stimulation induces the release of purines from the rabbit retina by a Ca²⁺- and energy-dependent process. Light flashes also induce a purine release. The results suggest an active role for adenosine in retinal neurotransmission.     

Specific binding of [3H]nitrendipine to membranes from coronary arteries and heart in relation to pharmacological effects. Paradoxical stimulation by diltiazem

High affinity binding sites for the calcium channel inhibitor [³H]nitrendipine have been identified in microsomes from pig coronary arteries (K_D=1.6 nM; B_max=35 fmol/mg) and in purified sarcolemma from dog heart (K_D=0.11 nM; B_max=230 fmol/mg). [³H]nitrendipine binding to coronary artery microsomes was completely inhibited by nifedipine, partially by verapamil and D600 and, surprisingly, was stimulated by d-cis-diltiazem but not by 1-cis-diltiazem, a less active isomer. Half-maximal relaxation of KCl-depolarized coronary rings occurred in a slow process at 1 nM nitrendipine or 100 nM d-cis-diltiazem. In dog trabecular strips, nitrendipine caused a negative inotropic response (ED₅₀=1μM). These results suggest that there may be multiple binding sites for different “subclasses” of calcium channel inhibitors, and that drug binding sites may be different molecular entities from the putative calcium channels.     

Comparative analysis of immune responses to Mycobacterium abscessus infection and its antigens in two murine models

Mycobacterium abscessus has been identified as an emerging pulmonary pathogen in humans. Because little is known regarding immune responses elicited by M. abscessus or its antigens, immunological responses were studied in two murine models subjected to intravenous (high-dose or systemic infection) or pulmonary (low-dose or local infection) inoculation with M. abscessus ATCC 19977. An overall comparison between the two models showed similar patterns of bacterial survival and host immune responses. The colonization of M. abscessus was the highest at 5 days post-infection (dpi) and its elimination was positively correlated with cell-mediated immunity in both challenges. However, an inverse relationship was observed between progressive inflammation and mycobacterial colonization levels in mice infected with a high dose at 14 dpi. Regarding antigens, culture filtrate (CF) of M. abscessus strongly induced IFN-γ secretion, whereas cellular extract (CE) antigen elicited strong antibody responses. The antibody response to M. abscessus antigens in mice subjected to low-dose infection increased when the cellular immune response decreased over 14 dpi. However, the antibody response for the high-dose infection increased promptly after the infection. In comparison of cytokine expression in lung homogenates after M. abscessus infection, Thl and Th2 cytokines increased simultaneously in the high-dose infection, whereas only cell-mediated immunity developed in the low-dose pulmonary infection. These findings not only enhance our understanding of the immune response to M. abscessus infection according to systemic or pulmonary infection, but may also aid in immunological diagnosis and vaccine development. M. abscessus, murine infection model, immune response, antigens, cytokines     

Chemical allatectomy of late Locusta embryos by a synthetic precocene and its effect on hopper morphogenesis

The anti-allatin substance, 7-ethoxy-precocene II (= “precocene III”) was topically applied to eggs of Locusta migratoria migratorioides with fully grown embryos in stage XX (about 64 ± 4% of the whole period of egg development). A day after precocene application the eggs were washed for 10–15 s in acetone and then transferred to clean containers for removing precocene residues and for preventing contamination at hatching. The treatment induced prothetelic morphogenetic disturbances which became overt in the subsequent hoppers; the effect was dose dependent and the ED₅₀ (= effective anti-allatin dose 50%) was low, 20.5 μg precocene III per g fresh egg weight (= 0.37 μg per egg). Quite similar results were obtained following application of precocene III to eggs with embryos in stage XXI (73 ± 4% of the egg development). These findings and direct examination of histological sections of the embryonic corpora allata demonstrated that precocene chemically allatectomizes late Locusta embryos. The lethal effect of precocene III was dependent on the washing. When the eggs were washed in acetone a day after application, mortality did not occur in a dose-dependent way; even the highest dose applied, 256 μg precocene III per egg (= 14405 μg per g fresh weight), was less than the LD₅₀ (lethal dose 50%). In contrast, without washing mortality was dose dependent, but it occurred later, at or after hatching; the LD₅₀ was 1334.9 μg per g (= 22.7 μg/egg). The results show that the late embryos are highly susceptible to the anti-allatin effect of the precocene, but are extremely insusceptible to its lethal effect; toward hatching, however, susceptibility to the lethal effect becomes marked.With doses between 45–14405 μg precocene III per g fresh egg weight, the anti-allatin effect became overt by a quite-uniform belated morphogenetic response. All hoppers which hatched from precocenetreated eggs were morphogenetically normal in the 1st instar and in the beginning of the 2nd instar, but the duration of the 2nd instar was almost doubled and at the end of this instar over 96% of the locusts died in the moult, being unable to shed the exuvia. Artificial removal of the apolyzed old cuticle revealed 3rd instar prothetelic adultiforms. These results and some data in the literature indicate that allatectomy of the embryo does not result in prothetelic morphogenetic disturbances in the 1st and early 2nd instar larvae and may impose the question what is the role of the juvenile hormone in late embryos and early larvae.     

Human erythrocyte glucose 6-phosphate dehydrogenase. Interaction with oxidized and reduced coenzyme

The complex between tetrameric glucose 6-phosphate dehydrogenase (G6PD) and four moles of structural NADP can bind four additional NADP equivalents with a K_diss of 0.85 μM. Alternatively, this complex shows a maximal binding capacity of two NADPH equivalents, with a corresponding K_diss of 0.1 μM. Therefore, a clear discrepancy has emerged from these spectrofluorimetric titrations with either the oxidized or the reduced form of the coenzyme, an “all-of-the-sites reactivity” being observed for NADP and a “half-of-the-sites reactivity” being conversely involved in NADPH binding.     

Synthesis and antitumor activity of 1-β-D-arabinofuranosylcytosine-5′-diphosphate-prednisolone and -cortisol

Superior antitumor activity and reduced toxicity of 1-β-arabinofuranosylcytosine (ara-C) conjugates of corticosteroids through a phosphodiester linkage have prompted us to synthesize the new ara-C conjugates of corticosteroids through a pyrophosphate diester linkage. Condensation of ara-CMP morpholidate with the steroid-21-monophosphates in pyridine at room temperature for 6 days and the subsequent separation on a DE-52 (formate) column using a linear gradient of 0?0.5 M triethylammonium formate (pH 7.0) gave ara-CDP-prednisolone (I) and ara-CDP-cortisol (II) in 37–55% yield. The conjugates were hydrolyzed to ara-CMP and the corresponding steroid-21-monophosphate by phosphodiesterase I. Conjugates I and II inhibited the $\text{in}\text{,}\text{vitro}$ growth of L1210 lymphoid leukemia by 50% (ED₅₀) at 0.03 and 0.08 μM, respectively, while ara-C and ara-CMP showed the respective ED₅₀ of 0.1 μM and 0.05 μM. Conjugates I and II exhibited ILS values of 116 and 86%, respectively, at 40 mg (53.7 μmole)/kg/day × 5 against L1210 leukemic mice, while that of ara-C at the nearly same dose (49 μmole/kg/day × 5) was 65%.     

Interactions of Nitric Oxide with Lipid Peroxidation Products under Aerobic Conditions: Inhibitory Effects on the Formation of Malondialdehyde and Related Thiobarbituric Acid-Reactive Substances

Under aerobic conditions, exposure of peroxidized lipids to nitric oxide (NO) was found to result in a rapid decrease in the levels of thiobarbituric acid-reactive substances (TBARS). Addition of 10–100 μM NO to rat brain homogenates preincubated for 2 h at 37°C caused up to a 20% decrease in the levels of TBARS compared to controls. A similar inhibitory effect was observed on TBARS produced by Fe²⁺-induced decomposition of 15-hydroperoxyeicosatetraenoic acid (15-HPETE), due apparently to NO-induced decomposition of the hydroperoxide (ferrous oxidation/xylenol orange assay). Prostaglandin G₂ (PGG₂, 35 μM), as a model bicyclic endoperoxide, and malondialdehyde (MDA, 20 μM), the main component of TBARS, proved also susceptible to degradation by NO or NO donors (diethylamine NONOate, DEA/NO) at concentrations of 100 μM or higher in 0.05 M phosphate buffer, pH 7.4, and at 37°C, as indicated by the reduced response to the TBA assay. No significant effect on TBARS determination was caused by nitrite ions. These and other data indicate that NO can inhibit TBARS formation by decomposing primary lipid peroxidation products, chiefly 15-HPETE and related hydroperoxides, and, to a lesser extent, later stage TBARS precursors, including bicyclic endoperoxides and MDA, via nitrosation and other oxidative routes, without however affecting chromogenic reactions during the assay.     

Effects of prostaglandin D2 on membrane potential in neuroblastoma X glioma hybrid cells as determined with a cyanine dye

A cyanine dye, diS-C₃-(5) was used to determine the effects of prostaglandins on the membrane potential in neuroblastoma X glioma cells (NG 108-15). The largest depolarization was seen with prostaglandin D₂ (ED₅₀ = 1.5 μM), and relative potencies of various prostaglandins (3 μM) were: D₂, 100; I₂, 41; E₁, 17; E₂, 7; and F_2α, 7. 5-Hydroxytryptamine in a dose over 100 μM also depolarized the membrane. The effect of prostaglandin D₂ was observed in a Na⁺-free medium or when Ca²⁺ was replaced by Sr²⁺. The addition of 3 mM ethylene-glycol-bis (β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid or 5 mM Co²⁺ partially inhibited the effects. These observations suggest that the depolarization of membrane by prostaglandin D₂ may primarily be related to alteration of Ca²⁺ permeability in the cell membrane.     

Effects of extremely-low-frequency magnetic fields on biological magnetite

Adair [Bioelectromagnetics 14:1–4, 1993] writes that “the effects of 60 Hz magnetic fields of 5 μT (50 mG) or less on biological structures holding magnetite (Fe₃O₄) are shown to be much smaller than those from thermal agitation; hence such interactions cannot be expected to be biologically significant.” This conclusion is questioned, because it appears to be based on a model that probably has very limited validity for pertinent biological systems. Furthermore, biologically plausible parameters can be selected to show that even this particular model does not exclude biologically significant effects of 60 Hz magnetic fields below 5 μT. Reported experimental results indicate effects in mammals of 50 Hz fields at the 1 μT level. © 1994 Wiley-Liss, Inc.     

ATP analogues and other phosphate compounds as gorging stimulants for Rhodnius prolixus

Five analogues of ATP and six other non-nucleotide compounds with phosphate groups were tested as gorging stimulants for second-instar larvae of Rhodnius prolixus to determine the importance of the phosphate chain. Only molecules with terminal phosphate groups were potent. Insertion of an imido group (5′-Adenylylimidodiphosphate, AMP-PNP) or a methylene group (β, γ-Methylene adenosine 5′-triphosphate, AMP-PCP) between the β and γ phosphates of ATP reduced the potency compared to ATP by ratios of 1.8 and 25.5, respectively. Substituting ribose (Adenosine 5′-diphosphoribose, AMP-PR) for the γ phosphate group or an amidate or a sulphate group (Adenosine 5′-phosphoramidate, AMP-N; Adenosine 5′-phosphosulphate, AMP-S) for the β and γ phosphate groups of ATP resulted in a complete loss of stimulatory activity.Some non-nucleotide phosphate compounds were potent phagostimulants. Pyrophosphate with an ED₅₀ of 64 μM had a potency ratio compared with ATP of 1:17. Methylene diphosphonic acid (ED₅₀ 680 μM) and even single phosphate ions (ED₅₀ 2.5 mM) had substantial potency. Two isomers of phosphoglyceric acid differ greatly in their ability to stimulate gorging; 2-PGA was active (ED₅₀ 160 μM) whereas 3-PGA had almost no activity.A summary of known phagostimulants to R. prolixus supports the hypothesis that ATP-like gorging stimulants act by forming a temporary binding to 3 sites on a receptor protein in the membrane of the chemosensory cell. The amino group on C₆ of adenine, the OH group on C₂ of ribose and the terminal phosphate group(s) determine potency, presumably by determining binding affinity. However, only the phosphate group appears essential to the chemosensory process.     

The action of four proposed chloride movement modifiers on acetylcholine responses of central neurones of Helix aspersa

1. Intracellular recordings were made from identified neurones in the visceral, (abdominal) ganglion of the snail, Helix aspersa. The hyperpolarising response of neurone E4 is a pure chloride event and has a reversal potential, (E_Cl), of −69.7 ± 1.7mV, (n = 4). This can be compared to depolarising responses of neurones E1 and E2 which are sodium mediated.2. Four membrane transport system antagonists, all thought to affect trans-membrane chloride movement, were investigated with respect to the two different acetylcholine responses described.3. Piretanide irreversibly blocks the hyperpolarising response in cell E4, (1–10 μM), increasing its inhibition with time but without changing E_Cl.4. Furosemide irreversibly blocks both types of acetylcholine responses at concentrations in the nanomolar range; no change in E_Cl or E_Na was associated with the inhibition but the “passive” membrane resistance appeared to decrease. Inhibition increased with time, normally causing a significant effect after 10–30 min.5. S.I.T.S. and ethacrynic acid appear very similar in effect; both reversibly block the two responses to acetylcholine and recovery after washing is virtually complete. The onset of antagonism is rapid and both compounds are slightly more effective against the hyperpolarising (“H”), response than the depolarising (“D”) response (threshold ∼10⁻⁵ M compared to ∼ 10⁻⁴ M). No change in E_Cl or E_Na was noted.6. Piretanide and furosemide probably exert their effect by interactions with the neuronal cell membrane, disrupting the integrity of this structure, whereas S.I.T.S. and ethacrynic acid may interact more specifically with the acetylcholine receptor protein.     

Characterization of the Electrogenic Sodium Channel from Rat Brain Membranes Using Neurotoxin-Dependent 22Na Uptake

The sodium channel was studied in osmotically-sensitive membrane preparations from rat brain and in innervated and chronically denervated rat soleus and extensor digitorum longus muscles. These experiments were undertaken in order to define a set of parameters for sodium channel function at the subcellular level to be used as a measure of retention of channel integrity upon subsequent isolation of the channel. Various neurotoxins and drugs were employed to control the permeability of the brain membranes to ²²Na and the sodium-conductance properties of the muscles. Batrachotoxin (ED₅₀ = 0.2 μM), veratridine (ED₅₀ = 1 μM), or grayanotoxin I (ED₅₀ = 30 μM) stimulated ²²Na uptake in brain membranes is inhibited in an apparently uncompetitive manner by the sodium channel blocking agents tetrodotoxin and saxitoxin in a simple competitive manner by Ca²⁺ and in a partial or allosteric competitive manner by lidocaine and procaine. This ²²Na uptake assay, which can be equated to a measure of equilibrium toxin binding, shows dependence on the concentration of the membranes and is sensitive to pH, temperature, ionic strength, and the ionic composition of the media. Parallel biophysical studies on sodium channels in rat muscle show that the properties of the sodium channel are similarly affected by these agents.     

Perturbations in polyamines and related enzymes following chlordecone-potentiated bromotrichloromethane hepatotoxicity

The mechanism by which chlordecone (CD) amplifies the hepatotoxicity of halomethanes such as CCl₄, CHCl₃, and BrCCl₃ has been a subject of intense study. Recent work has shown that suppression of hepatocellular regeneration leads to accelerated progression of liver injury leading to complete hepatic failure due to an unusual interaction between individually nontoxic low-dose combination of CD and CCl₄. Since polyamines are involved in cell division, their levels reflect the extent to which there is suppression of hepatocellular regeneration during CD and CCl₄ interaction. The present studies were designed to investigate the polyamine levels and associated enzymes in livers of rats treated with BrCCl₃ alone or CD and BrCCl₃ low-dose combination in order to confirm whether the sequence of events of hepatotoxicity is similar to that seen in CCl₄ toxicity or that seen during CD and CCl₄ interaction. The extent of liver toxicity in rats fed 10 ppm chlordecone (CD) for 15 days prior to the injection of a single low dose of BrCCl₃ (15 μL/kg body weight) or after exposure to a high dose of BrCCl₃ (80 μL/kg body weight) without CD pretreatment, was similar 6 and 24 hr later as assessed by plasma transaminase levels. There was also an increase in transaminase levels, in rats exposed to a single low dose of BrCCl₃ alone (15 μL/kg body weight) but this increase was far below the high-dose exposure alone or the combination treatment. Hepatic levels of ornithine decarboxylase, S-adeno-sylmethionine decarboxylase, N¹-acetylputrescine, N¹-acetylspermidine, putrescine, spermidine, and spermine at the end of 24 hr increased after exposure to a low dose of BrCCl₃ alone as compared to exposure to a high dose alone or the low-dose combination of CD and BrCCl₃. Liver spermidine N¹-acetyltrans-ferase was elevated at 2, 6, and 24 hr after exposure to a high dose of BrCCl₃ alone as compared to treatment with a low-dose combination of CD and BrCCl₃ suggesting decreased synthesis of this enzyme, in spite of a greater need as seen from liver transaminase levels. In general, it was observed that there is significant elevation in some polyamines and related enzymes during toxicity of a low dose of BrCCl₃ which seemed to stabilize within 24 hr. This was not observed with the other two groups of rats exposed either to BrCCl₃ high dose alone or the low-dose combination of CD and BrCCl₃. Results indicate that CD and BrCCl₃ low-dose combination treatment causes increased liver toxicity resulting in compromised polyamine metabolism which is coincidental with suppressed hepatocellular regeneration leading to accelerated progressive phase of liver injury culminating in complete hepatic failure. These findings point to the possibility that the mechanism of potenti-ation of BrCCl₃ hepatotoxicity by CD is similar to that seen for CD and CCl₄ interaction.     

Inhibition of nucleic acid synthesis in leukemia 1210 cells by antimetabolites of coenzyme Q10

Thirteen diversified antimetabolites of coenzyme Q₁₀ which have antitumor activity $\text{in vivo}$ were tested for inhibition of uptake of tritiated thymidine and uridine into DNA and RNA, respectively, of L1210 cells grown in tissue culture. Eight of these antimetabolites have inhibitory activities of the same order of magnitude as the used anticancer drugs, rubidazone and ellipticine. 5-ω-Phenylpropylmercapto-2,3-dimethoxy-1,4-benzoquinone was particularly potent to inhibit nucleic acid synthesis; ED₅₀ for DNA = 2.1 μM and ED₅₀ for RNA = 4.0 μM.     

In vitro delivery of curcumin with cholesterol-based cationic liposomes

A new cholesterol-based cationic lipid was synthesized; liposomes prepared on its basis were evaluated as drug delivery vehicles for curcumin. Free and liposome-encapsulated curcumin cytotoxicity against HeLa, A549, HepG2, K562 and 1301 cell lines was assessed. Liposomal curcumin with ED₅₀ values ranging from 2.5–10 μM exhibited 2–8 times higher cytotoxicity than free curcumin. The synthetic cholesterol-based cationic lipid also enhanced cellular uptake of curcumin into tested cells. Cationic liposome alone showed low cytotoxicity at high doses with ED₅₀ values of 90–210 μM.     

葛根素对正常产后小鼠泌乳作用的影响

摘要 目的：探究葛根素对产后正常小鼠泌乳作用的影响及其机制,并初步探究葛根素对产后正常小鼠的安全性。方法：将雌、雄KM小鼠以3:1比例合笼配种,得到孕鼠饲养至分娩。分娩后的小鼠随机分为正常对照组、葛根素低剂量（18 mg?kg^-1）、高剂量组（72 mg?kg^-1）,每组8只。从产后第3 d起,每天灌胃一次,共10 d。观察小鼠每日泌乳量变化,ELISA法检测血清中催乳素（PRL）、孕酮（P4）、雌二醇（E₂）含量,HE染色观察乳腺、肝、肾、子宫、卵巢组织病理学形态,Western Blot法检测乳腺组织中催乳素受体（PRLR）、酪氨酸激酶 2（JAK2）和信号传导与激活因子5a（STAT5a）的表达。结果：与正常对照组相比,从给药的第6天起,葛根素低剂量组的泌乳量显著升高（P＜0.05）;葛根素低、高剂量组均可见乳腺小叶内腺泡明显变大,分泌物明显增多,且低剂量组更为明显;葛根素低、高剂量组血清PRL水平明显升高（P＜0.01或P＜0.05）;葛根素低剂量组PRLR的蛋白表达明显增加（P＜0.01）,而葛根素高剂量组PRLR、JAK2的蛋白表达明显降低（P＜0.01）。葛根素低剂量组PRLR、JAK2、STAT5a的蛋白表达明显高于葛根素高剂量组（P＜0.01或P＜0.05）。结论：葛根素低剂量对产后正常小鼠有一定促进泌乳作用,高剂量时对泌乳作用不明显。葛根素低、高剂量均未对产后正常小鼠的肝、肾、卵巢和子宫产生明显的病理学改变。     

INFLUENCE OF ALUMINUM IN BIOLOGIC EFFECTS OF ELF MAGNETIC FIELD STIMULATION

We studied the influence of a weak, extremely low-frequency magnetic field (MF) with a frequency of 50 Hz and a peak amplitude of 103 μT and aluminum solution (in the form of AlCl₃) at different concentrations (0, 40, 70, 100, 130, 160, 400, 800, 2000, and 5000 μM) on the growth of spruce seedlings (Picea abies). The results showed that stimulatory and statistically significant MF effects on the growth of seedlings were observed only with a 100-μM aluminum solution. Slight stimulative effects were also observed within the range of concentrations between 40 and 160 μM Al³⁺ (all the stimulated groups taken together). Germination and fresh weight were not significantly influenced. At these concentrations the aluminum solution alone (without MF) or the MF alone (without Al³⁺) did not influence the growth parameters. These results suggest the importance of synergistic action of the MF with environmental factors as well as the existence of “physiologic windows” in addition to the frequency and power ones.