Prevalence and factors associated with the correlation between malnutrition and pain in hemodialysis patients.

Malnutrition and pain are common in patients with chronic kidney disease who undergo hemodialysis. Although both pain and malnutrition are associated with increased morbidity and mortality, few studies have explored the correlation between pain and nutritional status. This study aimed to investigate the factors associated with pain intensity in patients undergoing hemodialysis, focusing on the risk of malnutrition. This was a cross-sectional study conducted at a regional dialysis center in a large tertiary hospital. Convenience sampling was used to recruit adult patients who had undergone hemodialysis for more than three months. An interviewer-administered questionnaire was used to gather sociodemographic and clinical data related to dialysis status, comorbidities, and body mass index (BMI). Pain severity and pain interference with functioning domains of the Brief Pain Index (BPI) were used to assess pain, and the malnutrition inflammation score (MIS) was used to assess nutritional status. Descriptive and inferential statistics were used to report the findings. The data were analyzed using the 25th version of the Statistical Package for the Social Sciences (IBM-SPSS) software. Of the final sample of 230 patients, 63.0% were males and 37.0% were females, with an average age of 58.3 years. Almost one-third of the participants had a BMI within the normal range (33.9%), and nearly one-third had a BMI within the underweight range (33.9%). Slightly more than half had a normal nutritional status or mild malnutrition (54.8%), while just under half had moderate or severe malnutrition (45.2%). The prevalence of pain was 47.0%. At the multivariate level, the severity of pain was associated with malnutrition (p < 0.001). Pain interference with function was associated with marital status (p = 0.045), number of comorbidities (p = 0.012), and malnutrition (p < 0.001). The MIS was positively correlated with both the severity of pain and the interference score. Pain and malnutrition were found to be prevalent in patients undergoing hemodialysis. Pain severity was associated with malnutrition, and pain interference was associated with malnutrition, marital status, and the number of comorbidities. Hemodialysis treatment should follow a patient-tailored approach that addresses pain, nutritional status, and associated chronic conditions. In addition, pain assessment and management should be included in the curriculum of nephrology training programs.

Epidemiology and clinical characteristics of patients with healthcare-acquired multidrug-resistant Gram-negative bacilli: a retrospective study from a tertiary care hospital.

The numbers of infections caused by Gram-negative bacteria (GNB) that produce extended-spectrum beta-lactamases (ESBLs) and those that are carbapenem resistant, especially Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae), are increasing, and these infections are becoming a global public health problem. The aim of this study was to assess the prevalence of infections caused by ESBL-producing and carbapenem-resistant Gram-negative bacilli in patients hospitalized at An-Najah National University Hospital in Nablus, Palestine, and to provide healthcare workers with valuable information on the treatment of these infections. A retrospective cross-sectional investigation was conducted at a large tertiary care teaching hospital. The study included patients admitted to the hospital between January and December 2021, from whom ESBL-producing and carbapenem-resistant Gram-negative bacilli were isolated. The patients' clinical and demographic information was obtained from the hospital information system. In addition, information regarding the bacterial isolates and antibiotic resistance was obtained from the hospital's microbiology laboratory. This study included a total of 188 patients-91 males (48.4%) and 97 females (51.6%). The general surgical ward accounted for the highest proportion of infections (30.9%), followed by the surgical ICU (12.2%). The most common infections were caused by ESBL-producing E. coli, which accounted for 62.8% of the cases. Among them, urinary tract infections caused by this microorganism were the most prevalent (44.7% of patients). Over 50% of the patients (54.2%) had a history of antibiotic use, and 77.8% had been hospitalized within the past three months. ESBL-producing E. coli was significantly isolated from blood cultures (p-value = 0.000), and CR-K. pneumoniae was significantly isolated from endotracheal isolates (p-value = 0.001). This study emphasizes the concerning frequency of healthcare-acquired infections caused by ESBL-producing and carbapenem-resistant GNB in a tertiary care hospital. The substantial prevalence of antibiotic resistance presents considerable obstacles to the successful administration of routinely employed antibiotics. The results highlight the immediate need for improved antimicrobial stewardship and the implementation of infection control strategies to reduce the effects of multidrug-resistant GNB on patient well-being and public health.

Antibiotic resistance profiles and associated factors of Pseudomonas Infections among patients admitted to large tertiary care hospital from a developing country.

BACKGROUND: Pseudomonas infections are among the most common infections encountered in hospitalized patients, especially those with chronic illnesses or an immunocompromised state. Management of these infections has become challenging due to increased antibiotic resistance. Therefore, this study examines the antibiotic resistance profiles of Pseudomonas spp. and the associated factors among patients admitted to a large tertiary hospital in a developing country. METHODS: This retrospective observational chart review study assessed patients admitted to a large tertiary hospital in a developing country with a positive culture growth of Pseudomonas from anybody site. Antibiotic susceptibility of the isolated Pseudomonas and patient characteristics were studied from the start of 2021 to the end of 2022. The study ground consisted of 185 patients. RESULTS: The study included 185 patients with positive Pseudomonas isolates. Males constituted 54.6% of the sample, while 45.4% were females. The median age of the patients was 53 years. Patient comorbidities and risk factors for Pseudomonas infection and multidrug resistance were assessed. Antibiotic resistance to the Pseudomonas regimens showed the highest resistance to meropenem and ciprofloxacin (23.4%, similarly) among isolates of Pseudomonas aeruginosa. Multidrug resistance (MDR) was found in 108 (58.4%) isolates. The most commonly used antibiotic for treatment was piperacillin-tazobactam, accounting for 33.3% of cases, followed by aminoglycosides at 26.6%. CONCLUSIONS: Pseudomonas aeruginosa isolates were resistant to meropenem and ciprofloxacin. Over half of the isolates were multidrug-resistant, which was worrying. Piperacillin-tazobactam and aminoglycosides were the most often utilized antibiotics, highlighting the significance of susceptibility testing. Implementing antimicrobial stewardship programs and infection control measures can help reduce drug resistance and improve outcomes in Pseudomonas infections.

Nosocomial infections in the surgical intensive care unit: an observational retrospective study from a large tertiary hospital in Palestine.

BACKGROUND: Nosocomial infections or hospital-acquired infections are a growing public health threat that increases patient morbidity and mortality. Patients at the highest risk are those in intensive care units. Therefore, our objective was to provide a pattern analysis of nosocomial infections that occurred in an adult surgical intensive care unit (ICU). METHODS: This study was a retrospective observational study conducted in a 6-bed surgical intensive care unit (SICU) at An-Najah National University Hospital (NNUH) to detect the incidence of nosocomial infections from January 2020 until December 2021. The study group included 157 patients who received antibiotics during their stay in the SICU. RESULTS: The incidence of nosocomial infections, either suspected or confirmed, in the SICU was 26.9% (95 out of 352 admitted patients). Pneumonia (36.8%) followed by skin and soft tissue infections (35.8%) were the most common causes. The most common causative microorganisms were in the following order: Pseudomonas aeruginosa (26.3%), Acinetobacter baumannii (25.3%), extended-spectrum beta lactamase (ESBL)-Escherichia coli (23.2%) and Klebsiella pneumonia (15.8%). The average hospital stay of patients with nosocomial infections in the SICU was 18.5 days. CONCLUSIONS: The incidence of nosocomial infections is progressively increasing despite the current infection control measures, which accounts for an increased mortality rate among critically ill patients. The findings of this study may be beneficial in raising awareness to implement new strategies for the surveillance and prevention of hospital-acquired infections in Palestinian hospitals and health care centers.

Prevalence of chronic pain in hemodialysis patients and its correlation with C-reactive protein: a cross-sectional study.

End-stage renal disease (ESRD) is a common chronic disease worldwide that requires hemodialysis. Patients may face chronic pain and poor quality of life. Therefore, a better understanding of these variables in hemodialysis patients is essential to provide a good intervention. We aim to determine how common chronic pain is in hemodialysis patients and its correlation with sociodemographics, C-reactive protein (CRP), calcium, phosphorus, albumin, and parathyroid hormone. A cross-sectional study of hemodialysis patients was conducted in Palestine. Data collection took place between November 2020 and May 2021. We used the brief pain inventory score to assess chronic pain, and lab tests detected CRP levels. Data were collected using a convenience sampling technique. There were two hundred sixty-one patients in the present study. The mean age of the patients was 51 years, with 63.6% being men. 47.1% of them reported having chronic pain. Gender (p = 0.011), social status (p = 0.003), educational status (p = 0.010), and number of chronic diseases (p = 0.004) indicated a significant relationship with the severity score of pain. Furthermore, sex (p = 0.011), social status (p = 0.003), and number of chronic diseases (p = 0.002) were significantly associated with the pain interference score. Additionally, Person's test indicated significant correlations between CRP and pain severity (p < 0.001) and with pain interference (p < 0.001). Albumin was significantly and negatively correlated with pain severity (p = 0.001) and pain interference (p < 0.001). Multiple linear regression analysis revealed that patients who had a higher CRP level and many chronic diseases were more likely to have a higher pain severity score. However, pain severity was the only predictor for pain interference. Our results suggest that there is a significant correlation between the existence of chronic pain in hemodialysis patients and increased CRP levels. However, further investigations are needed with a larger number of patients in more than one dialysis unit to confirm this correlation and management of chronic pain in patients with HD.

Prevalence and Risk Factors of Group B Streptococcus Colonization in Pregnant Women: A Pilot Study in Palestine.

BACKGROUND: Maternal Streptococcus agalactiae (Group B Streptococcus (GBS)) colonization is an important cause of complications in mothers and neonates during gestation and after delivery. The data regarding GBS colonization among pregnant women in Palestine is scarce. The aim of this study is to determine the prevalence of GBS colonization, its associated risk factors, and the antibiotic sensitivity patterns in Nablus, West Bank, Palestine. METHODS: A cross-sectional, single center study conducted at Rafidia Governmental Hospital in Nablus, West Bank, Palestine. Samples were collected between November 2019 and January 2020. Vaginal swabs from 200 pregnant women (≥35 weeks of gestation) attending the labor and delivery department were plated directly on CHROMagarTM StrepB (CHROM agar, France) and placed in an incubator at 35-37°C. After 24 and 48 hours, the plates were checked for growth and classified into three categories: growth of GBS with mauve colonies on chromogenic media, no growth, or other growth. The identification of the mauve colonies was confirmed by the CAMP test. Identified GBS isolates were tested for susceptibility to vancomycin, ampicillin, clindamycin, cefotaxime, erythromycin, and levofloxacin using the disc diffusion method. Clinical and demographic information were collected using a questionnaire. RESULT: The overall prevalence of GBS colonization was 12%. The median age of the study population was 27 years. GBS colonization was significantly associated with age (p=0.013), history of previous preterm delivery (p=0.013), and parity (p=0.015). No association was noted with smoking, previous abortion, previous history of fetal demise, vaginitis, or urinary tract infection. Resistance to ampicillin, vancomycin, cefotaxime, erythromycin, clindamycin, and levofloxacin was found to be 91.7%, 54.2%, 45.8%, 29.2%, 25%, and 8.3%, respectively. CONCLUSION: The prevalence of vaginal GBS in this study was 12% from Nablus, West Bank. Further research is needed to determine the GBS serotypes common in West Bank and the burden they cause on the health system. Moreover, this study also highlights the need to establish a screening program suited to a developing country with low control on the antibiotic's prescription protocols.

Bibliometric analysis of global publications in medication adherence (1900-2017).

OBJECTIVES: Medication non-adherence is a worldwide problem. The aim of this study was to assess the global research output, research trends and topics that shaped medication adherence research. METHODS: A bibliometric methodology was applied. Keywords related to 'medication adherence' were searched in Scopus database for all times up to 31 December 2017. Retrieved data were analyzsd, and bibliometric indicators and maps were presented. KEY FINDINGS: In total, 16 133 documents were retrieved. Most frequently encountered author keywords, other than adherence/compliance, were HIV, hypertension, diabetes mellitus, schizophrenia, depression, osteoporosis, asthma and quality of life. The number of documents published from 2008 to 2017 represented 62.0% (n = 10 005) of the total retrieved documents. The h-index of the retrieved documents was 223. The USA ranked first (43.1%; n = 6959), followed by the UK (8.6%; n = 1384) and Canada (4.5%; n = 796). The USA dominated the lists of active authors and institutions. Top active journals in publishing research on medication adherence were mainly in the field of AIDS. Top-cited articles in the field focused on adherence to anti-HIV medications, the impact of depression on medication adherence and barriers to adherence. CONCLUSION: Adherence among HIV patients dominated the field of medication adherence. Research on medication adherence needs to be strengthened in all countries and in different types of chronic diseases. Research collaboration should also be encouraged to increase research activity on medication adherence in developing countries.

Bibliometric Analysis of Worldwide Publications on Antimalarial Drug Resistance (2006-2015).

BACKGROUND: In response to international efforts to control and eradicate malaria, we designed this study to give a bibliometric overview of research productivity in antimalarial drug resistance (AMDR). METHODS: Keywords related to AMDR were used to retrieve relevant literature using Scopus database. RESULTS: A total of 976 publications with an h-index of 63 were retrieved. The number of publications showed a noticeable increase starting in the early 1990s. The USA was the most productive country with 337 publications equivalent to one-third of worldwide publications in this field. More than two-thirds of publications by the USA (236, 70.03%) were made by international collaboration. Of the top ten productive countries, two countries were from Mekong subregion, particularly Thailand and Cambodia. The Malaria Journal was the most productive journal (136, 13.93%) in this field. Mahidol University (80, 8.20%) in Thailand was the most productive institution. Seven articles in the top-ten list were about artemisinin resistance in Plasmodium falciparum, one was about chloroquine resistance, one was about sulfadoxine-pyrimethamine resistance, and the remaining one was about general multidrug resistance. CONCLUSION: Eradication and control of AMDR require continuing research activity to help international health organizations identify spots that require an immediate action to implement appropriate measures.

Bibliometric analysis of worldwide scientific literature in mobile - health: 2006-2016.

BACKGROUND: The advancement of mobile technology had positively influenced healthcare services. An emerging subfield of mobile technology is mobile health (m-Health) in which mobile applications are used for health purposes. The aim of this study was to analyze and assess literature published in the field of m-Health. METHODS: SciVerse Scopus was used to retrieve literature in m-Health. The study period was set from 2006 to 2016. ArcGIS 10.1 was used to present geographical distribution of publications while VOSviewer was used for data visualization. Growth of publications, citation analysis, and research productivity were presented using standard bibliometric indicators. RESULTS: During the study period, a total of 5465 documents were published, giving an average of 496.8 documents per year. The h-index of retrieved documents was 81. Core keywords used in literature pertaining to m-Health included diabetes mellitus, adherence, and obesity among others. Relative growth rate and doubling time of retrieved literature were stable from 2009 to 2015 indicating exponential growth of literature in this field. A total of 4638 (84.9%) documents were multi-authored with a mean collaboration index of 4.1 authors per article. The United States of America ranked first in productivity with 1926 (35.2%) published documents. India ranked sixth with 183 (3.3%) documents while China ranked seventh with 155(2.8%) documents. VA Medical Center was the most prolific organization/institution while Journal of Medical Internet Research was the preferred journal for publications in the field of m-Health. Top cited articles in the field of m-Health included the use of mobile technology in improving adherence in HIV patients, weight loss, and improving glycemic control in diabetic patients. CONCLUSION: The size of literature in m-Health showed a noticeable increase in the past decade. Given the large volume of citations received in this field, it is expected that applications of m-Health will be seen into various health aspects and health services. Research in m-Health needs to be encouraged, particularly in the fight against AIDS, poor medication adherence, glycemic control in Africa and other low income world regions where technology can improve health services and decrease disease burden.

Bibliometric analysis of publications on Campylobacter: (2000-2015).

BACKGROUND: Campylobacter species are widespread zoonotic pathogens. Campylobacter jejuni causes a form of gastroenteritis called campylobacteriosis. Campylobacter drug resistance is considered a serious threat. In order to better understand national and international research output on Campylobacter, we conducted this bibliometric overview of publications on Campylobacter. This study can be used to assess extent of interaction and response of researchers, food regulators, and health policy makers to global burden of campylobacateriosis. METHODS: Scopus database was used to retrieve publications with the following keywords (Campylobacter/campylobacteriosis, C. jejuni, C. coli). The study period was set from 2000 to 2015. All types of journal documents, excluding errata, were considered. Bibliometric indicators such as annual growth of publications, country contribution, international collaboration, and citation analysis were presented. The quality of retrieved data was indirectly assessed by Hirsch index and impact factor of journals. RESULTS: A total of 5522 documents were retrieved with median (Q1-Q3) citations of 9 (2-23) and h-index of 113. Annual number of publications showed a fluctuating increase. The core leading journals were Applied and Environmental Microbiology journal and Journal of Food Protection with 246 (4.46%) publications for each. The USA (1309; 23.6%) was the most productive country while Danmarks Tekniske Universitet (150; 2.7%) was the most productive institution. Half of the top ten productive countries were European. France had the lowest percentage (33.5%) of articles with international collaboration while Netherlands (57.7%) had the highest percentage of articles with international collaboration. Approximately half (50.1%) of retrieved articles were published in journals under the subject area of "immunology/microbiology". Main themes in highly cited articles were molecular biology/genetics and public health burden of campylobacteriosis. There were 728 (13.1%) articles on campylobacter-related drug resistance, and the top cited articles focused mainly on increasing resistance to quinolones and fluoroquinolones. CONCLUSIONS: There was a clear increase in number of publications on Campylobacter. Rational use of antimicrobials in humans, poultry, and animals is highly recommended. International collaboration is highly required particularly in implementing new diagnostic screening technologies to minimize global health burden of Campylobacter and ensure food safety.

Bibliometric analysis of medicine-related publications on poverty (2005-2015).

BACKGROUND: Poverty is a global problem. The war against poverty requires not only financial support, but also poverty-related research to pinpoint areas of high need of intervention. In line with international efforts to fight poverty and negative consequences, we carried out this study to give a bibliometric overview of medicine-related literature on poverty. Such a s study is an indicator of the extent of interaction of various international key players on the war against poverty-related health problems. METHODS: Scopus was used to achieve the objective of this study. The time span set for this study was 2005-2015. Poverty-related articles under the subject area "Medicine" were used to give bibliometric indicators such as annual growth of publications, international collaboration, highly cited articles, active countries, institutions, journals, and authors. RESULTS: The total number of retrieved articles was 1583. The Hirsh-index of retrieved articles was 56. A modest and fluctuating increase was seen over the study period. Visualization map of retrieved articles showed that "HIV", infectious diseases, mental health, India, and Africa were most commonly encountered terms. No significant dominance of any particular author or journal was observed in retrieved articles. The United States of America had the largest share in the number of published articles. The World Health Organization and Centers for Disease Prevention and Control were among top active institutions/organizations. International collaboration was observed in less than one third of publications. Top cited articles focused on three poverty-related health issues, mainly, infectious diseases, malnutrition, and child development/psychology. Most of top articles were published in high impact journals. CONCLUSIONS: Data indicated that articles on poverty were published in high influential medical journals indicative of the importance of poverty as a global health problem. However, the number publications and the extent of international collaborations was lower than expected given the huge burden of poverty-related health problems.

Bibliometric analysis of global scientific research on carbapenem resistance (1986-2015).

BACKGROUND: Antimicrobial resistance is a global public health challenge and carbapenem resistance, in particular, is considered an urgent global health threat. This study was carried out to give a bibliometric overview of literature on carbapenem resistance. In specific, number of publications, top productive countries and institutes, highly cited articles, citation analysis, co-authorships, international collaboration, top active authors, and journals publishing articles on carbapenem resistance were analyzed and discussed. METHODS: Specific keywords pertaining to carbapenem resistance were used in Scopus database. Quantitative and qualitative analysis of retrieved data were presented using appropriate bibliometric indicators and visualization maps. RESULTS: A total of 2617 journal articles were retrieved. The average number of citations per article was of 21.47. The growth of publications showed a dramatic increase from 2008 to 2015. Approximately 9 % of retrieved articles on carbapenem resistance were published in Antimicrobial Agents and Chemotherapy journal. Retrieved articles were published by 102 different countries. The United States of America (USA) contributed most with 437 (16.70 %) articles followed by China with 257 (9.82 %) articles. When productivity was stratified by population size, Greece ranked first followed by France. Greece also ranked first when data were stratified by gross domestic product (GDP). Asian countries have lesser international collaboration compared with other countries in the top ten list. Five of top ten productive institutes were Europeans (France, the UK, Greece, Italy, and Switzerland) and two were Asians (China and South Korea). Other active institutes included an Israeli and a Brazilian institute. Four of the top ten cited articles were published in Antimicrobial Agents and Chemotherapy journal and two were published in The Lancet Infectious Diseases. CONCLUSION: There was a dramatic increase in number of publications on carbapenem resistance in the past few years. These publications were produced from different world regions including Asia, Europe, Middle East, and Latin America. International collaboration needs to be encouraged particularly for researchers in Asia. Molecular biology and epidemiology dominated the theme of the top ten cited articles on carbapenem resistance. This bibliometric study will hopefully help health policy makers in planning future research and allocating funds pertaining to carbapenem resistance.

Bibliometric analysis of worldwide publications on multi-, extensively, and totally drug - resistant tuberculosis (2006-2015).

BACKGROUND: The year 2015 marked the end of United Nations Millennium Development Goals which was aimed at halting and reversing worldwide tuberculosis (TB). The emergence of drug resistance is a major challenge for worldwide TB control. The aim of this study was to give a bibliometric overview of publications on multi-, extensively, and totally drug-resistant TB. METHODS: Scopus database was used to retrieve articles on multidrug resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) tuberculosis for the study period (2006-2015). The number of publications, top productive countries and institutions, citation analysis, co-authorships, international collaboration, active authors, and active journals were retrieved and analyzed. RESULTS: A total of 2260 journal articles were retrieved. The mean ± SD citations per article was 7.04 ± 16.0. The h-index of retrieved data was 76. The number of publications showed a three - fold increase over the study period compared with less than two - fold increase in tuberculosis research during the same study period. Stratified by number of publications, the United States of America ranked first while Switzerland ranked first in productivity per 100 million people, and South Africa ranked first in productivity stratified per one trillion Gross Domestic Product. Three of the High Burden Countries (HBC) MDR-TB (India, China, and South Africa) were present in top productive countries. High percentage of international collaboration was seen among most HBC MDR-TB. Except for Plos One journal, most active journals in publishing articles on MDR, XDR, TDR-TB were in infection - related fields and in general medicine. Top 20 cited articles were published in prestigious journal such as Lancet and New England Journal of Medicine. The themes in top 20 cited articles were diverse, ranging from molecular biology, diagnostic tools, co-infection with HIV, and results of new anti-TB drugs. CONCLUSION: Publications on MDR, XDR and TDR - TB are increasing in the past decade. International collaboration was common. Many low resourced African and Asian countries will benefit from research leading to new diagnostic and screening technology of TB. The exchange of expertise, ideas and technology is of paramount importance in this field.

Assessment of research productivity of Arab countries in the field of infectious diseases using Web of Science database.

BACKGROUND: To meet the future challenges of infectious diseases and limit the spread of multidrug resistant microorganisms, a better understanding of published studies in the field of infectious diseases is needed. The objective of this study was to analyze the quantity and quality of research activity in the field of infectious diseases in Arab countries and compare it with that in non-Arab countries. METHODS: Documents published in Arab countries within the research category of "infectious diseases" were extracted and analyzed using the Web of Science database. The data analyzed represent research productivity during the time interval between 1900 - 2012. RESULTS: Worldwide, the total number of documents published in the field of infectious diseases up to 2012 was 227,188. A total of 2,408 documents in the field of infectious diseases were published in Arab countries, which represents 1.06% of worldwide research output. Research output from Arab countries in the field of infectious diseases was low for decades. However, approximately a five-fold increase was observed in the past decade. Arab countries ranked 56(th) to 218(th) on the standard competition ranking (SCR) in worldwide publications in the field of infectious diseases. Egypt, with a total publication of 464 (19.27%) documents ranked first among Arab countries, while Kuwait University was the most productive institution with a total of 158 (6.56%) documents. Average citation per document published in Arab countries was 13.25 and the h-index was 64. Tuberculosis (230; 9.55%), malaria (223; 9.26%), and hepatitis (189; 7.8%) were the top three infectious diseases studied as according to the retrieved documents. CONCLUSION: The present data reveals that some Arab countries contribute significantly to the field of infectious diseases. However, Arab countries need to work harder to bridge the gap in this field. Compared with non-Arab countries in the Middle East, research output from Arab countries was high, but more efforts are needed to enhance the quality of this output. Future research in the field should be encouraged and correctly directed.

Gene regulation of alpha4beta2 nicotinic receptors: microarray analysis of nicotine-induced receptor up-regulation and anti-inflammatory effects.

alpha4beta2 Nicotinic acetylcholine receptors play an important role in the reward pathways for nicotine. We investigated whether receptor up-regulation of alpha4beta2 nicotinic acetylcholine receptors involves expression changes for non-receptor genes. In a microarray analysis, 10 muM nicotine altered expression of 41 genes at 0.25, 1, 8 and 24 h in halpha4beta2 SH-EP1 cells. The maximum number of gene changes occurred at 8 h, around the initial increase in (3)[H]-cytisine binding. Quantitative RT-PCR corroborated gene induction of endoplasmic reticulum proteins CRELD2, PDIA6, and HERPUD1, and suppression of the pro-inflammatory cytokines IL-1beta and IL-6. Nicotine suppresses IL-1beta and IL-6 expression at least in part by inhibiting NFkappaB activation. Antagonists dihydro-beta-erythroidine and mecamylamine blocked these nicotine-induced changes showing that receptor activation is required. Antagonists alone or in combination with nicotine suppressed CRELD2 message while increasing alpha4beta2 binding. Additionally, small interfering RNA knockdown of CRELD2 increased basal alpha4beta2 receptor expression, and antagonists decreased CRELD2 expression even in the absence of alpha4beta2 receptors. These data suggest that endoplasmic reticulum proteins such as CRELD2 can regulate alpha4beta2 expression, and may explain antagonist actions in nicotine-induced receptor up-regulation. Further, the unexpected finding that nicotine suppresses inflammatory cytokines suggests that nicotinic alpha4beta2 receptor activation promotes anti-inflammatory effects similar to alpha7 receptor activation.