Co-development of autoimmune hepatitis and Sj?gren's syndrome triggered by the administration of herbal medicines

Autoimmune hepatitis (AIH) has been reported in association with Sjögren''s syndrome (SS). Drug-induced AIH has been rarely reported. A rare case of the co-development of AIH and SS in a 53-year-old woman after the consumption of herbal medicines is described. After admission, the patient complained of dryness in her mouth, and she was subsequently diagnosed with SS, which had not been detected previously. The patient''s bilirubin and aminotransferase levels initially decreased following conservative management; however, they later began to progressively increase. A diagnosis of AIH was made based on the scoring system proposed by the International Autoimmune Hepatitis Group. The patient was administered a combination of prednisolone and azathioprine, and the results of follow-up liver-function tests were found to be within the normal range. This is an unusual case of AIH and SS triggered simultaneously by the administration of herbal medicines.     

Can patients’ preferences for involvement in decision-making regarding the use of medicines be predicted?

OBJECTIVE: The current study aimed to develop a model of patients' preferences for involvement in decision-making concerning the use of medicines for chronic conditions in the UK and test it in a large representative sample of patients with one of two clinical conditions. METHODS: Following a structured literature review, an instrument was developed which measured the variables that had been identified as predictors of patients' preferences for involvement in decision making in previous research. Five hundred and sixteen patients with rheumatoid arthritis or type 2 diabetes were recruited from outpatient and primary care clinics and asked to complete the instrument. RESULTS: Multivariate analysis revealed that age, social class and clinical condition were associated with preferences for involvement in decision-making concerning the use of medicines for chronic illness but gender, ethnic group, concerns about medicines, beliefs about necessity of medicines, health status, quality of life and time since diagnosis were not. In total, the fitted model explained only 14% of the variance. CONCLUSION: This study has demonstrated that current research does not provide a basis for predicting patients' preferences for involvement in decision-making. PRACTICE IMPLICATIONS: Building concordant relationships may depend on practitioners developing strategies to establish individuals' preferences for involvement in decision-making as part of the ongoing prescriber-patient relationship.     

Investigation of the “valency” of antibodies by means of azoproteins

Summary The valency of antibodies was studied by the method of exhaustion of antisera against mono-and diazoproteins, and subsequent cross reactions both with the antibodies left over in the supernatant fluid of the serum and with the precipitating and nonprecipitating antibodies isolated from the precipitate.It was proved that the antibodies interact with the antigens as multivalent compounds.The valency determined with regard to the azoproteins is dependent upon the number of groups introduced.Thus, bivalent antibodies correspond to monoazoproteins and trivalent ones to diazoproteins.The valency of antibodies is, evidently, determined by the structural similarity of the heterologous and the immunizing antigens as well as by the less complete specific conformity between the individual structural peculiarities of the antigen and its antibody.From the Tashkent Pharmaceutical Institute (Director-Docent M. A. Azizov)Presented by Active Member AMN SSSR N. N. Zhukov-Verezhnikov     

Modification of Uterotropic Effect of Estrogens by Whole-Body γ-Irradiation

The effect of -irradiation on the realization of the effects of estrogens was studied on rats treated with N-acetylcysteine, vitamins C and E, melatonin, and carnosine or subjected to forced swimming in a training mode. Irradiation (0.2 Gy) in combination with estrogens and without correction therapy induced genotoxic changes in the uterus, while irradiation in a higher dose (2 Gy) predominantly potentiated the hormonal effect of estrogens. Correction of the revealed abnormalities was achieved mainly with carnosine. The peculiarities of "estrogen toggle (re-targeting) effect" under the effect of -irradiation and its elimination differed from those induced by ethanol intake or tobacco smoking, which is important for understanding the mechanisms of hormone-induced carcinogenesis.     

Modification of α subunit of RIIA sodium channels by aconitine

The effect of aconitine (AC), an alkaloid toxin, on the electrophysiological properties of the rat brain type IIA alpha subunit expressed heterologously in the Chinese Hamster Ovarian (CHO) cell line was studied under the whole-cell patch-clamp configuration. The activation threshold of modified channels shifted by about -40 mV. As the number of depolarizations increased, the transient current at 0 mV decreased and, in proportion, the AC-modified current at -50 mV increased. This suggests a transition of channels to an AC-modified state. The rate of modification was nearly four times faster when 50 microM AC was applied internally than when applied in the bath solution. This supports the idea that the AC-binding site is located close to the cytoplasmic mouth of the channel pore. The AC-modified sodium currents inactivated completely, although with slower kinetics. The steady-state inactivation followed a simple Boltzmann function. AC-modified currents activated without a sigmoidal delay. The permeability of the NH4+ ion was enhanced such that its permeability ratio increased from an initial value of 0. 18 to 0.95 and for Cs+ it was enhanced from 0.03 to 0.07. These studies show that the AC-binding site resides at the pore region of the alpha subunit of the Na+ channel, and that the presence of beta subunit/s is not essential for AC binding.     

Regulation of NF-κB by deubiquitinases

The nuclear factor-κB (NF-κB) pathway is a critical regulator of innate and adaptive immunity. Noncanonical K63-linked polyubiquitination plays a key regulatory role in NF-κB signaling pathways by functioning as a scaffold to recruit kinase complexes containing ubiquitin-binding domains. Ubiquitination is balanced by deubiquitinases that cleave polyubiquitin chains and oppose the function of E3 ubiquitin ligases. Deubiquitinases therefore play an important role in the termination of NF-κB signaling and the resolution of inflammation. In this review, we focus on NF-κB regulation by deubiquitinases with an emphasis on A20 and CYLD. Deubiquitinases and the ubiquitin/proteasome components that regulate NF-κB may serve as novel therapeutic targets for inflammatory diseases and cancer.     

Medication information seeking behavior of patients who use multiple medicines: How does it affect adherence?

Objective

This article explores medication information seeking behavior (MISB). We aimed to develop a scale for measuring MISB and use it to explore the relationships between MISB, adherence and factors, which drive information seeking.

Methods

Patients (N = 910) using multiple medicines completed questionnaires. Exploratory and confirmatory factor analyses were performed. Correlations and multivariate analyses were used to investigate the relationships between variables.

Results

Respondents sought medication information mainly from health professionals and written medicines information. The medication information seeking behavior scale (MISB) had acceptable reliability and validity. Information seeking was most intense among respondents who had recent changes in their medicine regimen and worries about their medicines. Those who sought medication information from autonomous sources were more likely to be non-adherent than those who never did (OR = 2.00 [1.48, 2.70]). Seeking information from health professionals had no influence on adherence.

Conclusion

Health practitioners should carefully attend to patients’ questions about medicines information. When patients mention that they are worried about their medicines and have sought medication information from television, magazines, brochures or family and friends, this could be a sign that they tend towards non-adherent behavior.

Practice implications

The MISB scale could be used to learn more about patients’ use of medication information.     

Potentiation of Antitumor Effects of Cisplatin by Tumor Necrosis Factor-β

Recombinant tumor necrosis factor- potentiated the inhibitory effect of cisplatin on intramuscularly transplanted GA-1 tumor and liver metastasis in mice. The antitumor effect was related to cytotoxic and cytostatic activities of the test preparations rather than to initiation of apoptosis.     

Regulation of the activity of voltage-gated potassium channels by β subunits

Voltage-gated potassium channels may consist of two distinct types of subunits assembled in heteromultimeric complexes. One type of subunit, the α subunits, are sufficient to form the ion channel pore and the principal channel gating machinery. The second type of subunit, the β subunits, may have an auxiliary function, in particular in mediating rapid inactivation of voltage-gated potassium channels. Therefore, different α/β subunit compositions may generate voltage-gated potassium channels with properties distinct from the ones which are expressed by α subunits alone. The primary sequences of α subunits are structurally related and belong to a gene superfamily which may have evolved from a primordial ion channel gene. Similarly, β-subunit-related primary sequences have been identified in plants as well as in procaryotes. Possibly, primordial potassium channels were already assembled from α and βsubunits.     

Walking Pattern Recognition by Feature Vector of EMG

1.IntroductionIntheprocessofdevelopingintelligentprosthesis,EMGcontrollershavebeengettingmoreandmoreemphasisforitsvoluntarycontrolbytheamputee.EMGcontrolledupperextremityprostheseshavebeenconsideredforquitelongandusedquiteoften,butastothelowerlimbprostheses,especiallyabove-fleeprostheses,therearefewusageofEMGcondol.TheeffectivefeatureofEMGoflowerlimbduringlocomotionisveryimpoforEMGcontrolledabove-kneeprosthesisl'].BecauseofnonstationarityofEMGsignaloflowerlimbduringwalking,therearesomed…     

Selective inhibition of Hepatocarcinoma cells by apatite nanoparticles

In 1 994,Hideki Aoki and his colleagues happened to find that apatite (HAP)nanoparticlesinhibited growth of cancer cells when they tried to determine the possi-bility for HAP nanoparticles to act as tumor suppressing drugs carrier〔1〕.LaterShipu Li etal.…     

Biocompatibility of polypropylene surface-modified by COOH~ ion implantation

Polypropylene( PP) has become a much developed copolymer resin with desir-able mechanical properties,wear resistance as well as nontoxicity.But PP is quitedifferent from those developed biocompatable polymers in thatits chemical composi-tions contain only…     

Noncanonical Activation of β-Catenin by Porphyromonas gingivalis

Porphyromonas gingivalis is an established pathogen in periodontal disease and an emerging pathogen in serious systemic conditions, including some forms of cancer. We investigated the effect of P. gingivalis on β-catenin signaling, a major pathway in the control of cell proliferation and tumorigenesis. Infection of gingival epithelial cells with P. gingivalis did not influence the phosphorylation status of β-catenin but resulted in proteolytic processing. The use of mutants deficient in gingipain production, along with gingipain-specific inhibitors, revealed that gingipain proteolytic activity was required for β-catenin processing. The β-catenin destruction complex components Axin1, adenomatous polyposis coli (APC), and GSK3β were also proteolytically processed by P. gingivalis gingipains. Cell fractionation and Western blotting demonstrated that β-catenin fragments were translocated to the nucleus. The accumulation of β-catenin in the nucleus following P. gingivalis infection was confirmed by immunofluorescence microscopy. A luciferase reporter assay showed that P. gingivalis increased the activity of the β-catenin-dependent TCF/LEF promoter. P. gingivalis did not increase Wnt3a mRNA levels, a finding consistent with P. gingivalis-induced proteolytic processing causing the increase in TCF/LEF promoter activity. Thus, our data indicate that P. gingivalis can induce the noncanonical activation of β-catenin and disassociation of the β-catenin destruction complex by gingipain-dependent proteolytic processing. β-Catenin activation in epithelial cells by P. gingivalis may contribute to a proliferative phenotype.     

Stimulation of TNFα expression by hyperosmotic stress

Hyperosmotic stress is known to induce apoptotic cell death, an effect previously attributed to seemingly ligand-independent clustering of tumour necrosis factor alpha (TNF alpha) receptors. An alternative explanation for the clustering of TNF alpha receptors may be stimulation of TNF alpha production, with subsequent autocrine or paracrine stimulation of the receptors. The present study was performed to test for an effect of exposure to hyperosmotic extracellular fluid on cellular TNF alpha production. In both the macrophage cell line U937 and the B lymphocyte cell line LCL721, an increase of extracellular osmolarity to 500 mosmol/l indeed increased TNF alpha expression, an effect reversed by the p38 kinase inhibitor SB203580. In both cell types hyperosmotic stress triggered apoptosis, which in U937 cells was significantly inhibited by neutralizing antibodies against TNF alpha and by SB203580 and was similarly elicited by exogenous addition of TNF alpha. In contrast, osmotically induced apoptosis of LCL721 cells was only slightly blunted by anti-TNF alpha antibodies and rather increased by SB203580. In conclusion, through activation of p38 kinase hyperosmotic stress stimulates the expression of TNF alpha which at least in U937 macrophages may participate in the triggering of subsequent apoptotic cell death. However, the observations in LCL721 cells point to other, TNF alpha-independent, mechanisms mediating apoptotic cell death following an excessive increase of extracellular osmolarity.     

Segmentation of spatial experience by hippocampal θ sequences

The encoding and storage of experience by the hippocampus is essential for the formation of episodic memories and the transformation of individual experiences into semantic structures such as maps and schemas. The rodent hippocampus compresses ongoing experience into repeating theta sequences, but the factors determining the content of theta sequences are not understood. Here we first show that the spatial paths represented by theta sequences in rats extend farther in front of the rat during acceleration and higher running speeds and begin farther behind the rat during deceleration. Second, the length of the path is directly related to the length of the theta cycle and the number of gamma cycles in it. Finally, theta sequences represent the environment in segments or 'chunks'. These results imply that information encoded in theta sequences is subject to powerful modulation by behavior and task variables. Furthermore, these findings suggest a potential mechanism for the cognitive 'chunking' of experience.