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1.
Summary It has been suggested that local anesthetics may block sodium conductance through nervous membranes also by hydrophobic interaction, e.g., by expanding the membrane. Decreased anisotropy (fluidization) and depressed phase transition temperatures have been shown by relatively high local anesthetic concentrations. We studied the dose dependence of the effect of three clinically used local anesthetics, with different lipid solubility, on lipid fluidity parameters of four different model membranes. With stearic acid spin labels in dipalmitoyl lecithin vesicles etidocaine (1–5 mM) had the clearest fluidizing effect followed by bupivacaine (5 mM); 2-chloroprocaine was without effect on lipid fluidity. In synaptic plasma membranes a fluidizing effect near the hydrophilic part of the lipid bilayer was similar with etidocaine and bupivacaine (5–10 mM); 2-chloroprocaine had no effect. Bupivacaine at 125 and 250 M had a small ordering effect, which was not seen at a more hydrophobic site of the membrane. Etidocaine had the strongest fluidizing effect at the latter site of the synaptic plasma membranes. In erythrocyte ghost membranes, probed by stearic acid spin labels near the hydrophilic end, none of local anesthetics affected fluidity at 24° C, while at 37° C etidocaine (1–5 mM) and bupivacaine (5 mM) had a fluidizing effect. Dimyristoyl lecithin vesicles were probed by cis-and trans-parinaric acid. Etidocaine and bupivacaine (5–10 mM) clearly depressed the phase transition temperature evaluated from fluorescence intensity scans. The effect was most marked with bupivacaine (1–10 mM) when dis-parinaric acid was used. While isolated mammalian nerves are blocked by local anesthetic concentrations below 100 M, this study shows that the clinically used local anesthetics increase fluidity and depress phase transition temperature only at 10–100 times higher concentrations at physiological pH. This kind of hydrophobic membrane interaction may not be important for the nerve blocking effect. 相似文献
2.
Makoto Tanaka Aira Matsugaki Takuya Ishimoto Takayoshi Nakano 《Journal of bone and mineral metabolism》2016,34(2):234-241
Quantitative analysis of the orientational distribution of biological apatite (BAp) crystals is proposed as a new index of bone quality. This study aimed to analyze BAp c-axis orientation in ovariectomized (OVX) monkeys treated with amino-bisphosphonates minodronic acid and alendronate as reference. Sixty female monkeys aged 9–17 years were divided into five groups: one sham group and four OVX groups. The sham group and one OVX group were treated daily with vehicle for 17 months. The other three groups were treated daily with minodronic acid at doses of 0.015 and 0.15 mg/kg, and alendronate at 0.5 mg/kg orally, respectively. The seventh lumbar vertebrae were subjected to analysis of the preferential BAp c-axis orientation in the ventral cortical bone. The BAp c-axis orientation along the craniocaudal axis was significantly increased in the OVX monkeys. The high dose of minodronic acid suppressed the OVX-induced increase in the BAp c-axis orientation, whereas alendronate showed a non-significant tendency to suppress the increase in the orientation. In analysis with other parameters, the BAp c-axis orientation was positively correlated with bone formation indices in biochemical markers and bone histomorphometry and negatively correlated with the increase in lumbar bone mineral density. On the other hand, the BAp c-axis orientation was not correlated with bone resorption indices, except for the eroded surface. These results indicate that the increase in BAp c-axis orientation was ameliorated by minodronic acid treatment in OVX monkeys, mainly by suppression of bone formation increase. 相似文献
3.
Virtala AM Kunttu K Huttunen TA Virjo IO 《European journal of obstetrics, gynecology, and reproductive biology》2007,135(1):104-110
OBJECTIVE: To ascertain the current frequency of sexual intercourse, the current use of contraceptives, the ever use of emergency contraception, and the ever experience of condom failure among Finnish university students. STUDY DESIGN: The study population consisted of Finnish undergraduate university students (19-34 years of age) in 2004. The randomly selected sample comprised 5030 subjects. The data were collected by postal questionnaire, the response rate being 62.7%. Data were presented with frequency distributions and cross-tabulations. Chi-square test was used. Frequencies for women and men were presented and tested separately. RESULTS: A total of 80% of students were currently practicing sexual intercourse. Approximately half of the female students currently used hormonal contraception and one-third used a condom. Almost half of the men currently used a condom. The simultaneous use of condom and hormonal contraception was rare. Condom failure was common. The ever use of emergency contraception appeared to be associated with condom failure. CONCLUSION: Of Finnish university students 80% were sexually active and hormonal contraceptives were the most popular method of contraception among female students. The use of the condom should be practiced more often for prevention of sexually transmitted diseases. 相似文献
4.
Eiji Kawasaki Takahiro Fukuyama Aira Uchida Yoko Sagara Yuko Nakano Hidekazu Tamai Masayuki Tojikubo Yuji Hiromatsu Nobuhiko Koga 《Journal of diabetes investigation.》2022,13(4):738
Interleukin‐6 is a pleiotropic cytokine that plays a pathogenic role in type 1 diabetes. Therefore, anti‐interleukin‐6 receptor antibody, tocilizumab, used for the treatment of rheumatoid arthritis, is considered a candidate for immune intervention in type 1 diabetes. Here, we report the case of a 73‐year‐old woman (HLA‐DR9‐DQ3 homozygote) with well‐controlled rheumatoid arthritis who developed type 1 diabetes while receiving tocilizumab treatment. At 57 years‐of‐age, the patient was diagnosed with rheumatoid arthritis, for which she underwent tocilizumab therapy that enabled complete suppression of her joint inflammation. A total of 17 months after starting tocilizumab therapy, she noticed polydipsia, polyuria, general fatigue and weight reduction (−2 kg/month), and was diagnosed with type 1 diabetes with diabetic ketoacidosis based on an arterial pH of 7.26, serum ketone body of 7,437 μmol/L, blood glucose level of 925 mg/dL, glycated hemoglobin of 13.2% and the presence of anti‐islet autoantibodies. This case report shows valuable insight regarding the effect of anti‐interleukin‐6 receptor antibody therapy on type 1 diabetes prevention. 相似文献
5.
Toivgoogiin A Toyota M Yasuda N Ohara H 《Journal of epidemiology / Japan Epidemiological Association》2005,15(2):56-64
BACKGROUND: Few studies have examined the validity of administering tuberculosis control measures based on tuberculin skin test (TST) erythema measurement. The present study aimed to clarify the relationship between the erythema and the induration seen following TST and to evaluate the validity of diagnosing tuberculosis infection based on the erythema following TST in school-aged contacts who had been vaccinated with bacillus Calmette-Guérin (BCG) in infancy. METHODS: A 56-month longitudinal study from January 1999 through September 2003 followed 566 junior high school students in Kochi City who were contacts of an infectious tuberculosis case. To evaluate the diagnostic accuracy of the erythema and induration following TST of the contacts, false-positive and false-negative TST results were noted. RESULTS: The natural logarithm of the erythematous response size was linearly related to the induration size. When the size of the erythematous response was used to determine the presence of tuberculosis infection, the proportion of infected children increased with increasing exposure to the index case. When the TST results in the contact investigation were interpreted together with the change in the size of the erythematous response from that observed at the regular school-entry checkup, false positive test results were avoidable among the students who had a large erythematous response after the contact investigation TST, but whose response was only slightly larger than their erythematous response following the school-entry TST. Among the students whose TST results were negative, 1.9% developed tuberculosis. CONCLUSION: Both erythema and induration measurement were equally effective for identifying tuberculosis infection in schoolchildren vaccinated with BCG. 相似文献
6.
Determination of conformations and structures of opioid peptides in the membrane environments is an essential step to understand the action of the peptide to the specialized receptors. This information not only gains insight into the structure-function relationship of opioid peptide but also gives proper guidelines to design a new drug to have same neuroendocrine functions. This review provides the structural studies of three types of opioid peptide families such as enkephalin, beta-endorphin and dynorphin in the solid states and the membrane environments. The structures of enkephalins show that they take beta-bend, extended and double beta-bend structures in the crystals. Moreover, enkephalin molecules take a variety of structures in the crystals and are easily converted to the other structures with slightly different torsion angles. On the other hand, beta-bend structures are mostly seen in the membrane environments. Membrane bound structure of dynorphin shows that the N-terminus forms alpha-helical structure and is inserted into the membrane with the helical axis almost perpendicular to the membrane surface. It is discussed that the helical region of the extracellular loop II of the kappa-opioid receptor may interact with the helical region of dynorphin with a high affinity in the membrane environments. beta-endorphin takes alpha-helical structure at N-terminus and the central regions and the rest of regions take unordered structure when the bind to the membrane. Since the membrane bound structures of opioid peptides differ from those of the solution states, membrane association is an important process for exerting the affinity and the selectivity to the specific opioid receptors. 相似文献
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9.
A neonate with prune belly syndrome (congenital absence of the abdominal musculature associated with other malformations) is described and the main features reviewed. The most satisfactory explanation for this condition is an abnormality of development between the 3rd and 10th week of intrauterine life. 相似文献
10.
Kawasaki M Shiba T Shiba Y Yamaguchi Y Matsugaki N Igarashi N Suzuki M Kato R Kato K Nakayama K Wakatsuki S 《Genes to cells : devoted to molecular & cellular mechanisms》2005,10(7):639-654
GGA (Golgi-localizing, gamma-adaptin ear domain homology, ARF-binding) proteins, which constitute a family of clathrin coat adaptor proteins, have recently been shown to be involved in the ubiquitin-dependent sorting of receptors, through the interaction between the C-terminal three-helix-bundle of the GAT (GGA and Tom1) domain (C-GAT) and ubiquitin. We report here the crystal structure of human GGA3 C-GAT in complex with ubiquitin. A hydrophobic patch on C-GAT helices alpha1 and alpha2 forms a binding site for the hydrophobic Ile44 surface of ubiquitin. Two distinct orientations of ubiquitin Arg42 determine the shape and the charge distribution of ubiquitin Ile44 surface, leading to two different binding modes. Biochemical and NMR data strongly suggest another hydrophobic binding site on C-GAT helices alpha2 and alpha3, opposite to the first binding site, also binds ubiquitin although weakly. The double-sided ubiquitin binding provides the GAT domain with higher efficiency in recognizing ubiquitinated receptors for lysosomal receptor degradation. 相似文献