Two-way pharmacodynamic modeling of drug combinations and its application to pairs of repurposed Ebola and SARS-CoV-2 agents.

Existing pharmacodynamic (PD) mathematical models for drug combinations discriminate antagonistic, additive, multiplicative, and synergistic effects, but fail to consider how concentration-dependent drug interaction effects may vary across an entire dose-response matrix. We developed a two-way pharmacodynamic (TWPD) model to capture the PD of two-drug combinations. TWPD captures interactions between upstream and downstream drugs that act on different stages of viral replication, by quantifying upstream drug efficacy and concentration-dependent effects on downstream drug pharmacodynamic parameters. We applied TWPD to previously published in vitro drug matrixes for repurposed potential anti-Ebola and anti-SARS-CoV-2 drug pairs. Depending on the drug pairing, the model recapitulated combined efficacies as or more accurately than existing models and can be used to infer efficacy at untested drug concentrations. TWPD fits the data slightly better in one direction for all drug pairs, meaning that we can tentatively infer the upstream drug. Based on its high accuracy, TWPD could be used in concert with PK models to estimate the therapeutic effects of drug pairs in vivo.

Piperacillin-tazobactam induced immune hemolytic anemia led to increased renal impairment and eventual death from multiple organ failure in a patient with hypertensive nephropathy: case report and literature review.

BACKGROUND: Piperacillin is one of the most common drugs that cause drug-induced immune hemolytic anemia, but a complete description of the serological features and course of the disease is rare. This study completely describes the serological characteristics and course of a patient with hypertensive nephropathy who developed drug-induced immune hemolytic anemia and worsened renal function during repeated administration of piperacillin-tazobactam. CASE PRESENTATION: A 79-year-old male patient with hypertensive nephropathy who developed severe hemolytic anemia and worsened renal function during intravenous piperacillin-tazobactam anti-infective treatment due to lung infection. Serological tests showed that the result of the direct antiglobulin test for anti-IgG was positive (4 +) and anti-C3d was negative, and the irregular red blood cell antibody screening test was negative. Plasma samples collected at different times from 2 days before to 12 days after the discontinuation of piperacillin-tazobactam administration were incubated with piperacillin solution and red blood cells of O-type healthy blood donors at 37 °C, IgG piperacillin-dependent antibodies were detected, and the highest titer was 128. However, no tazobactam-dependent antibody was detected in any plasma samples. Therefore, the patient was diagnosed with piperacillin-induced immune hemolytic anemia. Although blood transfusion and continuous renal replacement therapy were given, the patient died of multiple organ failure 15 days after the administration of piperacillin-tazobactam was stopped. CONCLUSION: This is the first complete description of the disease course and serological changes of piperacillin-induced immune hemolytic anemia, which is bound to help deepen the understanding of drug-induced immune hemolytic anemia and draw profound lessons from it.

Progress in immune hemolytic anemia caused by drugs / 中国输血杂志

Drug-induced immune hemolytic anemia (DIIHA) is a rare cytopenia caused by damage to RBCs by drug-induced antibodies or non-immune protein adsorption (NIPA). The drugs associated with DIIHA and the mechanistic hypotheses that are thought to be involved have been controversial, with complex serological tests often required by specialized Immune Hematology laboratories for diagnosis. It is necessary to know the clinical manifestation and laboratory diagnosis of DIIHA in order to distinguish the immuno-hematological abnormality caused by drugs from other causes. How to improve the diagnostic ability of DIIHA and establish a scientific and reasonable idea of DIIHA serological examination is urgent to help clinical diagnosis and correct treatment.

β-Lactam antibiotics promoting aging and clearance of RBCs would deteriorate the DIIHA / 中国输血杂志

【Objective】 To analyze the influence of β-lactam antibiotics on RBC aging and clearance by detecting various indicators of aging and clearance on RBCs, as well as the differences in phagocytosis for erythrocytes before and after drugs treated in vitro. 【Methods】 RBCs were treated by β-lactam antibiotics, including Penicillin, Cefepime, Cefoperazone and Ceftazidime, and the changing of phosphatidylserine (PS) and clearance related CD markers, including CD35, CD47, CD55 and CD59 on the surface of the RBCs, were detected by flow cytometry at 0h and 24h after drugs treatment. The proportion of acanthocytes by microscope also at 0h and 24h after drugs treatment was calculated. The phagocytosis of drug-treated RBC was detected by monocyte monolayer assay (MMA). Untreated RBCs were incubated in PBS by the same condition as a negative control.The influence of β-lactam antibiotics on RBC aging and clearance by all the results above was studied. 【Results】 Compare to the untreated RBCs, the drug treated RBCs showed a higher PS level on the cell surface. The results showed by percentage as following(0 h vs 24 h): Penicillin 9.42% vs 93.30%, Cefepime 3.88% vs 57.27%, Cefoperazone 4.71% vs 75.75% and Ceftazidime 3.05% vs 43.19%. The acanthocytes ratio was as following(0 h vs 24 h): Penicillin 7.33% vs 86%, Cefepime 2.67% vs 52.67%, Cefoperazone 3.33% vs 67.67% and Ceftazidime 3.33% vs 90.67%. On the opposite, the clearance related CD markers, showed an obviously lower level after drugs treated(0 h vs 24 h): CD35: Penicillin 7.36% vs 11.87%, Cefepime 0.14% vs 28.51%, Cefoperazone 11.85% vs 21.55% and Ceftazidime 7.63% vs 8.73%; CD47: Penicillin 1.22% vs 9.13%, Cefepime 1.80% vs 0.86%, Cefoperazone 0.08% vs 6.85% and Ceftazidime 1.54% vs 5.50%; CD55: Penicillin 14.46% vs 44.31%, Cefepime 17.27% vs 38.41%, Cefoperazone 19.28% vs 33.28% and Ceftazidime 14.62% vs 34.13%; CD59: Penicillin 4.71% vs 20.56%, Cefepime 4.03% vs 7.60%, Cefoperazone 5.91% vs 22.38% and Ceftazidime 5.93% vs 30.89%. Drug-treated RBCs attached more to monocytes than untreated RBCs. 【Conclusion】 The β-lactam antibiotics could induce the changing of PS and the clearance of related CD markers on surface of RBCs. They also could lead acanthocytes and make the RBCs more susceptible to phagocytosis by monocytes. The β-lactam antibiotics could promote the RBCs aging and clearance, which might deteriorate the DIIHA.

Ear Acupuncture Points in Neonates From Drug-Dependent Mothers: A Prospective Study.

Aim: The aim of the study was to determine the presence or absence of ear acupuncture points (EAP) in newborn children with or without neonatal abstinence syndrome (NAS) and to confirm the hypothesis that neonates with NAS have more EAP than healthy neonates. Methods: We conducted a prospective case control study with ethical consent at the University Children's Hospital, Division of Neonatology Bern and the Department of Gynecology and Obstetrics Inselspital Bern in Switzerland. We determined the EAP in n = 26 newborn children born to drug-dependent mothers compared with n = 50 healthy newborns. For the detection of EAP, we used an ear point detection pen. EAP are present only if weakness exists in the corresponding area. Results: Twenty-six neonates who were born to drug-dependent mothers and developed NAS were screened on the 5th day after delivery (range 1-22). The median Finnegan Score was 12 points (range 6-18) on the day of examination. Twenty-four active EAP were detected on the left earlobe and 25 were detected on the right earlobe. There was no significant difference between the right and left lobes (p = 0.9285, two tailed test) and the number of acupuncture points. The correlation between the Finnegan Score and the number of EAP was highly significant (p = 0.0001). The most common active points were the psycho-vegetative rim of the reflex zone of sympathicus and parasympathicus. Organic points were also commonly detected. The urinary bladder, kidney and hip points were detected with a frequency of 12-15%. The shen men pain point was found in three neonates, and the point of desire as a psychological point, was also detected. The correlation between sex and active EAP was highly significant (p = 0.0093, Mann-Whitney test for the left earlobe and p = 0.0025 for the right earlobe). Boys had a significantly higher number of EAP than girls. All NADA points were detected in the neonates born to drug-dependent mothers, and the most frequent point was the vegetative point. Healthy neonates showed only the vegetative point in the vegetative rim 1/3 among the NADA points. A comparison of newborns born to drug-dependent mothers and 50 healthy neonates showed that the former group had statistically significantly more active points. For the left earlobe, the difference between neonates born to drug-dependent mothers and controls was statistically significant (p = 0.0008, Mann-Whitney test). Highly similar results were found for the right earlobe (p = 0.0001, Mann-Whitney test). Discussion: Our current work confirms that neonates born to drug-dependent mothers with high Finnegan scores and NAS have more EAP than healthy neonates. The vegetative rim is the most common point as shown in our previous studies. Our observations showed that twins had similar but not identical points; each individual had unique points depending on health status. Newborn boys with NAS had a higher number of EAP than newborn girls in the neonatal intensive care unit. This findings may be attributed to the reserve of newborns with NAS. Newborn girls are considered more robust than boys in the neonatal care setting. EAP in neonates might potentially be used for diagnosis and therapeutic opinions in neonates in the future.

Clinical Efficacy of Modified Qilang Prescription in Treatment of Drug-dependent Constipation with Qi and Yin Deficiency and Its Effect on MTL， VIP， 5-HT， and 5-HT4R in Peripheral Blood / 中国实验方剂学杂志

Objective:To investigate the curative efficacy of modified Qilang prescription on drug-dependent constipation with Qi and Yin deficiency and the effects on serum vasoactive intestinal peptide （VIP）， motilin （MTL）， 5-hydroxytryptamine （5-HT）， and 5-hydroxytryptamine 4 receptor （5-HT4R）. Method:A total of 160 patients diagnosed with drug-dependent constipation were randomly divided into a treatment group （<italic>n</italic>=80， Qilang prescription） and a control group （<italic>n</italic>=80， lactulose oral solution）. The treatment lasted for eight weeks. Changes in clinical symptoms， traditional Chinese medicine （TCM） syndrome， and serum VIP， MTL， 5-HT， and 5-HT4R before and after treatment were observed. The clinical efficacies of the two groups were compared. An eight-week follow-up was carried out for the observation of recurrent rate and TCM syndrome. Result:The overall response rate of the treatment group （90.91%） was higher than that （75.00%） of the control group<italic> </italic>（<italic>Z</italic>=-6.514，<italic>P</italic><0.05）. There was no significant difference in serum VIP， MTL， 5-HT， and 5-HT4R between the two groups before treatment. After treatment for eight weeks， both groups showed reduced serum VIP level as compared with those before treatment， and the treatment group was inferior to the control group （<italic>P</italic><0.05）. The serum MTL levels of the two groups were both higher than those before treatment （<italic>P</italic><0.05）， and the treatment group was superior to the control group （<italic>P</italic><0.05）. After treatment， the level of 5-HT in the treatment group was higher than that in the control group （<italic>P</italic><0.05）. The post-treatment 5-HT4R level in the treatment group slightly increased （<italic>P</italic><0.05）， but no significant difference in 5-HT4R levels between the two groups after treatment was observed. During the eight-week follow-up， the recurrence rate in the treatment group was significantly lower than that in the control group at the 2nd and 4th weeks （<italic>P</italic><0.05）. There was no significant difference in the recurrence rate between the treatment group ［57.14% （40/70）］ and the control group ［64.81% （35/54）］ after eight weeks. Conclusion:Modified Qilang prescription was superior to lactulose in the short- and mid-term efficacy on drug-dependent constipation with Qi and Yin deficiency. No significant difference in the long-term efficacy was observed. The underlying therapeutic mechanism might be related to the regulation of serum VIP， MTL， 5-HT， and 5-HT4R levels.

Drug-induced immune hemolytic anemia investigation: Comparison between tube test and microcolumn agglutination (gel test) for the detection of drug-dependent antibodies in the presence of soluble drug.

OBJECTIVES: Testing for drug-dependent antibodies is traditionally performed with the tube method either with drug-treated red blood cells or with untreated red blood cells in the presence of soluble drug. Gel microcolumn agglutination method was compared to tube testing for the demonstration of drug-dependent antibodies in the presence of soluble drug. MATERIALS AND METHODS: Patient's samples were tested in parallel by tube and gel microcolumn agglutination method with untreated and/or enzyme-treated red blood cells in the presence of soluble drug. RESULTS: Twenty six different patient's samples were studied and thirty nine tests performed to investigate antibodies directed against fifteen different drugs. There was a good correlation between the results obtained by tube and gel method in terms of analytical sensitivity and specificity. Reactions appeared to be stronger with the gel test than seen with the conventional tube method for most of the drug antibodies investigated. Enzyme-treated cells should be used in addition to untreated cells to improve the sensitivity of the method for detecting drug-dependent antibodies especially those directed against drugs that do not bind firmly to red blood cells. CONCLUSIONS: Gel method appeared to be sensitive, reliable, reproducible, and comparable to the conventional tube method for the detection of all the drug-dependent antibodies investigated in this study. Further studies need to be performed to evaluate gel testing for the detection of drug-dependent antibodies that only react with drug-treated red blood cells.

Acquired Glanzmann thrombasthenia: From antibodies to anti-platelet drugs.

In contrast to the inherited platelet disorder given by mutations in the ITGA2B and ITGB3 genes, mucocutaneous bleeding from a spontaneous inhibition of normally expressed αIIbß3 characterizes acquired Glanzmann thrombasthenia (GT). Classically, it is associated with autoantibodies or paraproteins that block platelet aggregation without causing a fall in platelet count. However, inhibitory antibodies to αIIbß3 are widely associated with primary immune thrombocytopenia (ITP), occur in secondary ITP associated with leukemia and related disorders, solid cancers and myeloma, other autoimmune diseases, following organ transplantation while cytoplasmic dysregulation of αIIbß3 function features in myeloproliferative and myelodysplastic syndromes. Antibodies to αIIbß3 occur during viral and bacterial infections, while drug-dependent antibodies reacting with αIIbß3 are a special case. Direct induction of acquired GT is a feature of therapies that block platelets in coronary artery disease. This review looks at these conditions, emphasizing molecular mechanisms, therapy, patient management and future directions for research.

Metronidazole caused profound drug-induced immune thrombocytopenia.

Metronidazole is commonly prescribed and has not been known to cause drug-induced immune thrombocytopenia. We have provided clinical and laboratory evidence with DDabs that metronidazole can cause drug-induced immune thrombocytopenia (DITP). Providers must be aware of metronidazole causing DITP because recognition of thrombocytopenia is critical and cessation of the drug should occur promptly.

Overdose prevention training with naloxone distribution in a prison in Oslo, Norway: a preliminary study.

BACKGROUND: Prison inmates face a ten times increased risk of experiencing a fatal drug overdose during their first 2 weeks upon release than their non-incarcerated counterparts. Naloxone, the antidote to an opioid overdose, has been shown to be feasible and effective when administered by bystanders. Given the particular risk that newly released inmates face, it is vital to assess their knowledge about opioid overdoses, as well as the impact of brief overdose prevention training conducted inside prisons. METHODS: Prison inmates nearing release (within 6 months) in Oslo, Norway, voluntarily underwent a brief naloxone training. Using a questionnaire, inmates were assessed immediately prior to and following a naloxone training. Descriptive statistics were performed for main outcome variables, and the Wilcoxon signed-rank test was used to compare the participants' two questionnaire scores from pre-and post-training. RESULTS: Participating inmates (n = 31) were found to have a high baseline knowledge of risk factors, symptoms, and care regarding opioid overdoses. Nonetheless, a brief naloxone training session prior to release significantly improved knowledge scores in all areas assessed (p < 0.001). The training appears to be most beneficial in improving knowledge regarding the naloxone, including its use, effect, administration, and aftercare procedures. CONCLUSIONS: Given the high risk of overdosing that prison inmates face upon release, the need for prevention programs is critical. Naloxone training in the prison setting may be an effective means of improving opioid overdose response knowledge for this particularly vulnerable group. Naloxone training provided in the prison setting may improve the ability of inmates to recognize and manage opioid overdoses after their release; however, further studies on a larger scale are needed.

Fabrication of SnO2/porous silica/polyethyleneimine nanoparticles for pH-responsive drug delivery.

To create novel nanocarriers for achieving excellent drug delivery performance, pH-responsive fluorescent porous silica (PS) nanocarriers were developed by encapsulating SnO2 nanoparticles and coating polyethyleneimine (PEI) layer. SnO2/porous silica (SnO2/PS) nanoparticles have an average diameter of 80nm and center-radial large pore channels. The large channels endow them high surface area with a Brunauer-Emmett-Teller (BET) area of 939m(2)g(-1). Aspirin was used as test drug to evaluate the releasing behavior of SnO2/porous silica/polyethyleneimine (SnO2/PS/PEI) nanoparticles. Results indicated that aspirin can be successfully incorporated into the SnO2/PS/PEI nanoparticles and the SnO2/PS/PEI nanoparticles displayed excellent pH-responsive release. The release rate in pH7.4 buffer is higher than that in pH5.5 buffer, which attributed to the PEI structure change in varied pH buffer. In addition, the SnO2/PS/PEI nanoparticles presented novel drug-dependent fluorescence, which could be used to trace the drug release.

Variability of Findings in Drug-Induced Immune Haemolytic Anaemia: Experience over 20 Years in a Single Centre.

BACKGROUND: Drug-induced immune haemolytic anaemia (DIHA) is difficult to diagnose, and its true incidence remains obscure. Here, we present cases of DIHA identified at our institute over the last two decades. METHODS: Serological tests were performed according to standard procedures. Detection of drug-dependent antibodies was performed in the presence and absence of the relevant drug and/or their ex vivo antigens. RESULTS: Over the last 20 years, 73 patients have been identified with DIHA in our institute, which was related to 15 different drugs. The most common single drugs identified were diclofenac (n = 23), piperacillin (n = 13), ceftriaxone (n = 12) and oxaliplatin (n = 10). As far as data were available, haemolysis was acute in all patients, and signs of intravascular haemolysis were present in 90% of the cases. Haemolysis resulted in death in 17 patients (23%). The remaining patients recovered, but haemolysis was complicated by transitory renal and/or liver failure or shock in 11 patients. Upon initial evaluation, the antibody screening test was positive in 36 cases. A positive direct antiglobulin test (DAT) at least with anti-C3d was found in 65 cases, with anti-IgG only in 6 cases, and with anti-IgA only in 1 case. CONCLUSION: DIHA is a rare but potentially life-threatening disorder that should be considered if a patient develops haemolysis under drug treatment. The main serological finding is a positive DAT, primarily with anti-C3d.

Serviços de saúde e comunidades terapêuticas: há uma relação em prol do dependente químico? / Health services and therapeutic communities: is there a relationship for the drug-dependent patient?

O uso de droga é um dos principais problemas de saúde pública em todo o mundo. Para o auxílio no tratamento aos dependentes químicos existem no Brasil alguns serviços, dentre eles se encontram as comunidades terapêuticas que são instituições não governamentais que devem funcionar de forma articulada com a atenção básica de saúde e com os Centros de Atenção Psicossocial (CAPS). O objetivo deste estudo foi analisar o relacionamento entre as Comunidades Terapêuticas com os serviços de atenção à saúde. Foram pesquisadas 43 comunidades localizadas no município de Goiânia-GO, sua região metropolitana e também a cidade de Anápolis-GO. O trabalho de campo foi realizado por meio da aplicação do questionário. Todas as comunidades visitadas faziam uso do Sistema Único de Saúde (SUS) e, na contramão desse constante uso, identificou-se que não há uma relação efetiva entre as comunidades e os CAPS. As comunidades possuem o direito e o dever de proporcionar aos residentes o acesso ao SUS garantidos por lei. Já o CAPS como instituição de serviço voltado para o tratamento e reinserção social dos usuários de drogas serviria como um pilar, juntamente, com as comunidades no auxílio ao dependente químico. A relação entre os serviços de saúde e as comunidades pesquisadas se apresenta, em princípio, a favor dos dependentes químicos. No entanto, há a necessidade de haver uma maior interlocução entre os serviços de saúde, principalmente os CAPS e as comunidades visando a reabilitação integral dos residentes.

One of the main problems in public health is the use of illicit drugs. Several services are an aid in the treatment of illicit drugdependent people among which may be mentioned the therapeutic communities. They are non-governmental organizations which function together with the Basic Health Care and with Centers for Psychosocial Care (SAPS). Current analysis deals with the relationship between therapeutic communities and Health Services available at the National Health Service (SUS). Forty-three communities were researched in the municipality of Goiânia GO Brazil, the metropolitan region and the city of Anápolis GO Brazil. Field work was undertaken with a questionnaire. All communities visited use SUS services, but there is no relationship between the communities and CAPS. Communities have the right and the duty to provide resident people access to SUS, which is warranted by law. As a service institution for the treatment and social reinsertion of illicit drug users, CAPS is an important institution for communities in their aid for the drug user. The relationship between health service and communities is primarily for drug dependent people. However, greater interlocution must exist between the communities and CAPS for the integral rehabilitation of residents.

Platelet-activating protamine-heparin-antibodies lead to higher protamine demand in patients undergoing cardiac surgery.

OBJECTIVES: Platelet-activating antibodies against protamine-heparin-complexes were described in patients undergoing cardiac surgery, but their clinical consequences remain unclear. This prospective single-center observational study aimed to describe the prevalence and clinical consequences of protamine-heparin-complex antibodies in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: A total of 200 patients undergoing cardiac surgery with cardiopulmonary bypass were included. Blood samples were collected preoperatively and 1 hour, 24 hours, and 7 days after weaning from cardiopulmonary bypass. All sera were tested for the presence of protamine-heparin-complex antibodies using a modified heparin-induced platelet-activation assay. Specific Fcγ receptor IIa-dependent platelet activation was confirmed by repeated testing in the presence of the Fcγ receptor IIa-blocking antibody IV.3. RESULTS: Samples from 185 patients were obtained, of whom 24 patients (13%) were positive for protamine-heparin-complex antibodies preoperatively. In all positive samples, functional reactivity was reversible in the presence of IV.3. Although patients with a preoperative presence of protamine-heparin-complex antibodies were significantly older compared with patients negative for protamine-heparin-complex antibodies (73 ± 9.8 years vs 68 ± 10 years, P = .037), no other potential risk factors were identified at 1 day before operation. Patients with protamine-heparin-complex antibodies required significantly more protamine to neutralize heparin (47.66 mg vs 41.67 mg, P = .027). Protamine-heparin-complex antibodies have no significant influence on perioperative platelet numbers, bleeding complications, transfusion requirement, thromboembolic events, major cardiovascular and cerebrovascular events, inflammation parameters, or kidney function. CONCLUSIONS: Protamine-heparin-complex antibodies occur frequently in patients undergoing cardiac surgery on cardiopulmonary bypass, resulting in specific platelet activation in vitro. Protamine-heparin-complex antibodies are associated with increased protamine requirement after cardiopulmonary bypass and possibly slower recovery of platelet numbers.

Drug-dependent behaviors and nicotinic acetylcholine receptor expressions in Caenorhabditis elegans following chronic nicotine exposure.

Nicotine, the major psychoactive compound in tobacco, targets nicotinic acetylcholine receptors (nAChRs) and results in drug dependence. The nematode Caenorhabditis elegans' (C. elegans) genome encodes conserved and extensive nicotinic receptor subunits, representing a useful system to investigate nicotine-induced nAChR expressions in the context of drug dependence. However, the in vivo expression pattern of nAChR genes under chronic nicotine exposure has not been fully investigated. To define the role of nAChR genes involved in nicotine-induced locomotion changes and the development of tolerance to these effects, we characterized the locomotion behavior combining the use of two systems: the Worm Tracker hardware and the WormLab software. Our results indicate that the combined system is an advantageous alternative to define drug-dependent locomotion behavior in C. elegans. Chronic (24-h dosing) nicotine exposure at 6.17 and 61.7µM induced nicotine-dependent behaviors, including drug stimulation, tolerance/adaption, and withdrawal responses. Specifically, the movement speed of naïve worms on nicotine-containing environments was significantly higher than on nicotine-free environments, suggesting locomotion stimulation by nicotine. In contrast, the 24-h 6.17µM nicotine-treated worms exhibited significantly higher speeds on nicotine-free plates than on nicotine-containing plates. Furthermore significantly increased locomotion behavior during nicotine cessation was observed in worms treated with a higher nicotine concentration of 61.7µM. The relatively low locomotion speed of nicotine-treated worms on nicotine-containing environments also indicates adaption/tolerance of worms to nicotine following chronic nicotine exposure. In addition, this study provides useful information regarding the comprehensive in vivo expression profile of the 28 "core" nAChRs following different dosages of chronic nicotine treatments. Eleven genes (lev-1, acr-6, acr-7, acr-11, lev-8, acr-14, acr-16, acr-20, acr-21, ric-3, and unc-29) were significantly up-regulated following 61.7µM nicotine treatment, in which worms showed significantly increased locomotion behavior. This study provides insights into the linkage between nicotine-induced locomotion behavior and the regulation of nicotinic acetylcholine receptors.

A case of oxaliplatin-induced immune-mediated thrombocytopenia.

Oxaliplatin is a platinum compound used in patients with gastrointestinal malignancies. It is known to evoke a drug-induced immune-mediated thrombocytopenia, which has not been reported in Korea. We describe a 53-year-old man who developed oxaliplatin-induced immune-mediated thrombocytopenia during chemotherapy for colon cancer. Oxaliplatin-dependent IgG platelet antibodies were detected in his serum on flow cytometry. He was treated with immunoglobulin and corticosteroids without any complications. Physicians should consider oxaliplatin-induced immune-mediated thrombocytopenia, when a sudden, isolated thrombocytopenia develops during chemotherapy with oxaliplatin.

CHIP-MYTH: a novel interactive proteomics method for the assessment of agonist-dependent interactions of the human ß2-adrenergic receptor.

G-protein coupled receptors (GPCRs) are involved in a variety of disease processes and comprise major drug targets. However, the complexity of integral membrane proteins such as GPCRs makes the identification of their interacting partners and subsequent drug development challenging. A comprehensive understanding of GPCR protein interaction networks is needed to design effective therapeutic strategies to inhibit these drug targets. Here, we developed a novel split-ubiquitin membrane yeast two-hybrid (MYTH) technology called CHIP-MYTH, which allows the unbiased characterization of interaction partners of full-length GPCRs in a drug-dependent manner. This was achieved by coupling DNA microarray technology to the MYTH approach, which allows a quantitative evaluation of interacting partners of a given integral membrane protein in the presence or absence of drug. As a proof of principle, we applied the CHIP-MYTH approach to the human ß2-adrenergic receptor (ß2AR), a target of interest in the treatment of asthma, chronic obstructive pulmonary disease (COPD), neurological disease, cardiovascular disease, and obesity. A CHIP-MYTH screen was performed in the presence or absence of salmeterol, a long-acting ß2AR-agonist. Our results suggest that ß2AR activation with salmeterol can induce the dissociation of heterotrimeric G-proteins, Gαßγ, into Gα and Gßγ subunits, which in turn activates downstream signaling cascades. Using CHIP-MYTH, we confirmed previously known and identified novel ß2AR interactors involved in GPCR-mediated signaling cascades. Several of these interactions were confirmed in mammalian cells using LUminescence-based Mammalian IntERactome (LUMIER) and co-immunoprecipitation assays. In summary, the CHIP-MYTH approach is ideal for conducting comprehensive protein-protein interactions (PPI) screenings of full-length GPCRs in the presence or absence of drugs, thus providing a valuable tool to further our understanding of GPCR-mediated signaling.

A case of oxaliplatin-induced immune-mediated thrombocytopenia

Oxaliplatin is a platinum compound used in patients with gastrointestinal malignancies. It is known to evoke a drug-induced immune-mediated thrombocytopenia, which has not been reported in Korea. We describe a 53-year-old man who developed oxaliplatin-induced immune-mediated thrombocytopenia during chemotherapy for colon cancer. Oxaliplatin-dependent IgG platelet antibodies were detected in his serum on flow cytometry. He was treated with immunoglobulin and corticosteroids without any complications. Physicians should consider oxaliplatin-induced immune-mediated thrombocytopenia, when a sudden, isolated thrombocytopenia develops during chemotherapy with oxaliplatin.

Colonization of Bacteria on Pharynx among Different Groups of People / 中华医院感染学杂志

OBJECTIVE To understand the pharynx colonization and drug resistance among normal population,drug-dependent people and mentally ill people.METHODS There were 3 groups divded.The health care workers were the randomly selected to group A of forced detoxification 299 specimen from throat swab were collected from the drug dependent people(in stage group B 199 examples),and the mentally ill people(group C,99 examples).The throat swab samples were inoculated into the blood agar,MacConkey and XV/phenylethanol double-plate,and cultured commonly and anaerobic allg at the same time,and the strains were identified and the sensitivity was tested.RESULTS From the three groups,Haemophilus influenzae,H.parainfluenzae,Staphylococcus aureus and other strains.were detected out But in group B were detected out Haemophilus paranaemolyticus,Klebsiella pneumoniae subsp ozaenae and Pseudomonas aeruginosa strains.Pantoea agglomerans,Serratia marcescens,and A streptococcus were detected out in group C.CONCLUSIONS In the three group similar types of pharyngeal bacteria were found the colonization rates of different strains among the three groups are different,the resistance is also different,The work is in favor to provide a reliable basis for clinical treatment.