Low physical activity, fatigue and depression in breast cancer survivors: Moderation by levels of IL-6 and IL-8.

BACKGROUND AND AIMS: Although previous studies suggested that depressed mood and fatigue among cancer survivors are associated with chronic inflammation, the effect of cytokines on the relation between physical activity and fatigue and depressed mood is characterized by inconsistent results. The aim was to examine levels of pro-inflammatory (IL-6, IL-8, TNFα, IL-12) and anti-inflammatory (IL-10) cytokines in relation to the effects of physical activity on fatigue and depressed mood. METHODS: Breast cancer survivors (n = 108; stages I-III), aged >20 and who were 1-6 months postchemotherapy were recruited consecutively. Participants completed the Fatigue Symptom Inventory and Center for Epidemiologic Studies Depression Scale and reported physical activity details; 10 cc of blood were drawn for assessment of levels of IL-6, IL-8, IL-10, Il-12, and TNFα in serum. RESULTS: Only IL-6 and IL-8 were associated with fatigue and depressed mood. Controlling for background variables, physical activity and IL-6 were significantly associated with fatigue, but only physical activity was significantly associated with depressed mood. A moderated effect of IL-6 and IL-8 was found in the association of physical activity and fatigue, indicating that this association is significant only in individuals with lower levels of IL-6 or IL-8. CONCLUSIONS: Fatigue and depressed mood are differently associated with pro-inflammatory cytokines. In addition, IL-6 and IL-8 are main cytokines affected by physical activity. The study stresses the need to provide information and tailored guidance for cancer survivors for maintaining an active lifestyle into survivorship and the importance of allocating resources for programs to encourage active lifestyles among cancer survivors. Caution should be exercised in the interpretation of the results due to the cross-sectional design and possibility of bidirectional associations between the study variables.

Stability and change of postchemotherapy symptoms in relation to optimism and subjective stress: A prospective study of breast cancer survivors.

OBJECTIVES: Inconsistent findings were reported about the course of postchemotherapy symptoms; specifically, the effect of changes in optimism and perception of subjective stress on the evolution of symptoms remains understudied. This prospective study aimed (a) to examine the course of postchemotherapy symptoms of emotional distress, fatigue, and cognitive difficulties among breast cancer survivors and (2) to assess the effect of changes in optimism and subjective stress on the trajectory of these symptoms. METHODS: Ninety-eight breast cancer survivors, diagnosed at stages I to III, aged 30 to 74, recruited consecutively (response rate 84.7%) completed fatigue, emotional distress, self-reported cognitive difficulties, optimism, and subjective stress questionnaires at three points in time: upon enrollment (1-6 months after completing treatment, Time 1) posttreatment, 6 months (Time 2), and 12 months (Time 3). A linear mixed-effects model was used to analyze the data. RESULTS: Emotional distress decreased between time-points, level of cognitive difficulties remained stable, and a marginal decrease in fatigue was evident. Optimism or subjective stress predicted changes in each of the symptoms (P<.01), except for the effect of optimism on cognitive difficulties (P=.06). The interactions between time and optimism and between time and subjective stress were only significant regarding their effect on emotional distress (P<.05), showing that the strongest effect of these variables was at Time 2. CONCLUSION: The course of postchemotherapy symptoms shows patterns of stability and change over a 1-year period. Optimism and subjective perceptions of stress were shown to affect the decrease of symptoms. Therefore, these two factors should be specifically targeted in psycho-social interventions.

Cancer-related fatigue and depression in breast cancer patients postchemotherapy: Different associations with optimism and stress appraisals.

OBJECTIVE: Symptoms of depression and cancer-related fatigue (CRF) are common among breast cancer patients postchemotherapy and may seriously impair quality of life (QoL). This study aimed to assess the relationship between depression and CRF in breast cancer patients postchemotherapy and to examine their relationships to optimism and to threat and challenge appraisals. METHOD: Participants included 95 breast cancer patients (stages 1-3) 1 to 6 months after completion of chemotherapy. Patients submitted personal and medical details and completed the following: physical symptom questionnaires (EORTC QLQ-C30, and QLQ-BR23), a symptoms of depression questionnaire (CES-D), the Fatigue Symptom Inventory (FSI), the Life Orientation Test (LOT-R), and a stress appraisals questionnaire. RESULTS: We found levels of depression, CRF, and appraisals of cancer as a threat to bemoderate and levels of optimism and appraisals of cancer as a challenge to be high. Depression and CRF were positively associated. A multivariate regression analysis revealed that 51% of the CRF variancewas explained; physical symptoms and threat appraisal were significantly associated with CRF. A 67% of the CRF variance of depression was explained; challenge and threat appraisals were significantly associated with depression [corrected]. SIGNIFICANCE OF RESULTS: Although CRF and depression were often experienced simultaneously and both were found to be higher among individuals who gave higher appraisals of cancer as a threat, only depression was related to optimism and challenge appraisals, while CRF was related mainly to intensity of physical symptoms. The different pattern of associations between optimism and appraisals warrants further clinical attention as well as future study.

Human amnion membrane as a substrate for the detection of autoantibodies in pemphigus vulgaris and bullous pemphigoid.

BACKGROUND: Human amnion membrane (HAM) was suggested to be a superior antigenic substrate for immunoblotting in detecting autoantibodies of autoimmune bullous skin diseases. OBJECTIVES: To determine the properties of HAM as an antigenic substrate for the detection of autoantibodies in pemphigus vulgaris and bullous pemphigoid. METHODS: Immunomapping and tandem liquid chromatography mass spectrometry were used to delineate the antigenic structure of HAM. Immunoblotting and indirect immunofluorescence were used to study the diagnostic utility of HAM in 25 pemphigus patients, 41 pemphigoid patients, and 36 controls, and the results were compared to those of indirect immunofluorescence on monkey esophagus, immunoblotting using normal human skin, and enzyme-linked immunosorbent assay. RESULTS: Immunomapping demonstrated the presence of all the antigens known to be targeted in autoimmune bullous skin diseases, in both normal human skin and HAM, except for the absence of BP230, and low threshold levels of Dsg1, Dsg3 and Dsc3 in HAM. HAM indirect immunofluorescence demonstrated anti-basement membrane zone antibodies in 48.7% of the pemphigoid patients, and anti-intercellular space antibodies in 72.0% of the pemphigus patients. HAM immunoblotting did not demonstrate anti-BP230 antibodies, but detected anti-BP180 antibodies in 53.7% of the pemphigoid patients. It did not demonstrate anti-Dsg1 and/ or anti-Dsg3 antibodies in any of the pemphigus patients. These results were inferior to those of ELISA and monkey esophagus indirect immunofluorescence. CONCLUSIONS: Compared to other studied methods, HAM does not offer advantages in detecting autoantibodies in bullous pemphigoid and pemphigus vulgaris.

Cytokine levels (IL-4, IL-6, IL-8 and TGFß) as potential biomarkers of systemic inflammatory response in trauma patients.

PURPOSE: Much research is now being conducted in order to understand the role of cytokines in the development of the inflammatory response following trauma. The purpose of this study was to evaluate whether serum levels of certain cytokines, measured immediately after initial injury, can be used as potential biomarkers for predicting the development and the degree of severity of the systemic inflammatory response (SIRS) in patients with moderate and severe trauma. METHODS: We conducted a prospective study with 71 individuals of whom 13 (18.3 %) were healthy controls and 58 (81.7 %) were traumatized orthopaedic patients who were categorized into two groups: 31 (43.6 %) with moderate injuries and 27 (38.1 %) patients with severe orthopaedic trauma. Thirty cc of heparinized blood were drawn from each individual within a few hours after the injury. Serum levels of pro-inflammatory, regulatory and anti-inflammatory cytokines were measured in each individual participant. RESULTS: High levels of pro-inflammatory cytokines IL-1ß,-6,-8,-12, tumour necrosis factor alpha and interferon gamma were found in all injured patients compared to healthy controls. Only IL-6 and IL-8 were significantly higher in the injured patients. Levels of the regulatory cytokines, transformed growth factor beta (TGF-ß) and IL-10 were higher in the injured patients, but significant only for TGF-ß. Levels of IL-4 were significantly lower in the injured groups as compared to the controls. CONCLUSIONS: Secretion of large amounts of pro-inflammatory cytokines and decreased level of anti-inflammatory cytokines during the acute phase of trauma may lead to the development of systemic inflammatory response syndrome (SIRS) in unstable polytraumatized patients. SIRS may result in life threatening conditions as acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF). High levels of IL-6, IL-8, TGFß and low levels of IL-4 were found to be reliable markers for the existence of immune reactivity in trauma patients. More research is needed to study pattern of cytokine levels along the acute period of injury, after surgical interventions and during recovery.

Possible association of Toll-like receptor 9 polymorphisms with cytokine levels and posttraumatic symptoms in individuals with various types of orthopaedic trauma: early findings.

BACKGROUND: Although TLR9 polymorphisms may be associated with cytokine dysregulation, its role in regulation of cytokines due to bodily trauma or in relation to acute stress symptoms or posttraumatic stress symptoms (ASS/PTS) has not been evaluated. AIMS: To assess serum cytokine levels and levels of ASS and PTS in relation to four common TLR9 single-nucleotide polymorphisms (SNPs) in individuals with various types of orthopaedic trauma. METHODS: Forty-eight accident-injured individuals, aged 20-60 years were studied. Serum cytokine levels and TLR9 SNPS (1486T/C, 1237T/C, 1174G/A and 2848G/A) were assessed together with intensity of ASS and PTS symptoms. RESULTS: Statistically significant higher serum levels of IL-12 and IL-1ß (p<.05) were found in individuals heterozygous for TLR9-1237 (TC) than in individuals expressing the most common TLR9-1237 type (TT), while differences in levels of IL-6 were not significant. Also, marginally significant levels of IL-6 were found in individuals expressing the common TLR9-1174 (GG) compared with individuals homozygous (AA) or heterozygous (GA) for this SNP. They also had non-significant higher intensity of ASS symptoms. A trend of higher PTS levels in individuals expressing the most common type TLR9-1174 (GG) was found, contrary to homozygous (AA) and heterozygous individuals (GA). CONCLUSIONS: The results of this pilot study suggest that accident-injured individuals with certain TLR9 polymorphisms express higher levels of pro-inflammatory cytokines (IL-1ß, IL-6 and IL-12). The associations of TLR9 SNPSs with increased risk of ASS or PTS should be further studied in larger groups of such patients.

[Crucial risk factors for renal function deterioration of HIV-infected patients at the AIDS Clinic in Rambam Hospital].

BACKGROUND: Since the introduction of new and efficient antiretroviraL treatment (ART), mortality and morbidity due to HIV infections have been greatly reduced. However, there is a growing incidence of chronic diseases, such as cardiovascular, metabolic, bone and renal diseases. OBJECTIVES: To examine the impact of HIV infection on renal functions over time and to define risk factors which contribute to the change in renal functions. METHODS: We screened 600 out of the 800 patients who are registered in the Institute for Immunology, Allergy and AIDS at the Rambam Medical Center, Haifa. We collected data from the typed and computerized medical fites of the patients. Finally, for 136 patients under surveillance between the years 2005-2010 there was sufficient data to meet the inclusion and exclusion criteria. We followed the renal function, presented by the estimated glomerular filtration rate (eGFR) and quantified the change in GFR each year. Then, we determined the risk factors contributing to the change in renal function, by using a multi-variant model. RESULTS: We found an average yearly decline of 4.83 mt/ min/1.73 m2 body surface area during the period 2005- 2010. We also found that co-infection with HCV and treatment by the antiretrovirat drug Tenofovir are significantly associated with the decline in renal function among our patients [p=0. 0.14 and 0.045 respectively). CONCLUSIONS: There is a persistent decline in renal function, overtime, in HIV patients. This decline is significantly higher than the change observed in age- and sex-matched healthy general populations. Co-infection with HCV and treatment by the antiretroviral drug Tenofovir are substantial risk factors for eGFR.

[Fertility and HIV: equal opportunity for everyone].

Highly active antiretroviral treatment (HAART), the increase in life expectancy and improved HIV viral detection methods, have all led to a change in attitude towards fertility in people living with HIV. There is now acknowledgment of the fundamental rights of HIV patients to parenthood and growing implementation of assisted fertility in this group. The aims of fertility treatment are prevention of infection in HIV-discordant couples, and treatment for fertility problems, identical to the general population. We review the influence of HIV on the reproduction systems of males and females, conditions requiring fertility intervention, various methods that are possible and describe the optional treatment existing in Israel for patients with viral infection, and specifically HIV.

Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy.

BACKGROUND: HIV subtypes A and CRF01_AE (A/AE) became prevalent in Israel, first through immigration of infected people, mostly intravenous-drug users (IVDU), from Former Soviet-Union (FSU) countries and then also by local spreading. We retrospectively studied virus-transmission patterns of these subtypes in comparison to the longer-established subtype B, evaluating in particular risk-group related differences. We also examined to what extent distinct drug-resistance patterns in subtypes A/AE versus B reflected differences in patient behavior and drug-treatment history. METHODS: Reverse-transcriptase (RT) and protease sequences were retrospectively analyzed along with clinical and epidemiological data. MEGA, ClusalX, and Beast programs were used in a phylogenetic analysis to identify transmission networks. RESULTS: 318 drug-naive individuals with A/AE or patients failing combination antiretroviral therapy (cART) were identified. 61% were IVDU. Compared to infected homosexuals, IVDU transmitted HIV infrequently and, typically, only to a single partner. 6.8% of drug-naive patients had drug resistance. Treatment-failing, regimen-stratified subtype-A/AE- and B-patients differed from each other significantly in the frequencies of the major resistance-conferring mutations T215FY, K219QE and several secondary mutations. Notably, failing boosted protease-inhibitors (PI) treatment was not significantly associated with protease or RT mutations in either subtype. CONCLUSIONS: While sizable transmission networks occur in infected homosexuals, continued HIV transmission among IVDU in Israel is largely sporadic and the rate is relatively modest, as is that of drug-resistance transmission. Deviation of drug-naive A/AE sequences from subtype-B consensus sequence, documented here, may subtly affect drug-resistance pathways. Conspicuous differences in overall drug-resistance that are manifest before regimen stratification can be largely explained in terms of treatment history, by the different efficacy/adherence limitations of older versus newer regimens. The phenomenon of treatment failure in boosted-PI-including regimens in the apparent absence of drug-resistance to any of the drugs, and its relation to adherence, require further investigation.

Vitamin D status in young HIV infected women of various ethnic origins: incidence of vitamin D deficiency and possible impact on bone density.

BACKGROUND: Decreased bone mineral density (BMD) was reported in HIV infected patients. Mechanisms leading to this decrease are poorly understood. AIMS: To assess factors relating to BMD in young HIV infected Israeli women of Ethiopian and Caucasian origin. PATIENTS AND METHODS: 75 young HIV infected women aged 34.5 ± 8.5 followed up at the Institute of Allergy, Clinical Immunology & AIDS filled a questionnaire about sun exposure, daily calcium intake and dress habits. Data about HIV status and treatment regimens were collected from the patients' charts. Serum hydroxyvitamin D [25(OH)D] levels, bone turnover markers and bone densitometry were evaluated. RESULTS: 28 (65%) of Ethiopians and 2 (6.25%) of Caucasians had 25(OH)D serum levels <10 ng/ml (vitamin D deficiency), p = 0.001. 21 (67.7%) Ethiopians and 16 (39%) Caucasians avoided sun exposure, p = 0.019. Mean daily calcium intake was 491 ± 268.6 mg and 279 ± 252.6 mg, respectively, p = 0.001. Z scores < -1 found at Lumbar spine in 26 (89.7%), at Femoral neck in 20 (69%) at Total hip in 17 (58.6%) of vitamin D deficient patients compared to 20 (48.8%), 17 (41.5%), 9 (22%), in patients with 25(OH)D > 10 ng/ml, p < 0.01, <0.03, <0.001, respectively. Significantly more Ethiopian than Caucasian women covered their face (32.3% and 9.5%, p = 0.003) and hands (58.1% and 30.9%, p = 0.03). There was no difference in bone turnover markers levels. CONCLUSION: Poorer vitamin D status was observed in Ethiopian women might be one of the important factors related to lower BMD in this group.

Human factors-focused reporting system for improving care quality and safety in hospital wards.

OBJECTIVE: The aim was to develop a reporting system for collecting human factors problem reports to establish a database to guide activities for improving health care quality and patient safety. BACKGROUND: The current error and incident report systems do not provide sufficient and adequate coverage of the factors contributing to impaired safety and care quality. They fail to examine the range of difficulties that clinical staff encounters in the conduct of daily work. METHOD: A voluntary problem-reporting system was developed to be used by hospital wards' clinicians and was tested in four wards of two hospitals in Israel. The system is based on human factors--formatted problem reports submitted by physicians and nurses on difficulties and hazards they confront in their daily work. Reports are grouped and evaluated by a team of human factor professionals. RESULTS: A total of 359 reports were collected in the wards during 12 weeks, as compared with a total of 200 incidents reports that were collected during a period of 5 years with the existing obligatory incident reporting system. In-depth observational studies conducted on the wards confirmed the ability of the new system to highlight major human factors problems, differentially identifying specific problems in each of the wards studied. Problems reported were directly related to general factors affecting care quality and patient safety. CONCLUSION: Validation studies confirmed the reliability of the reporting system in pinpointing major problems per investigated unit according to its specific characteristics. APPLICATION: This type of reporting system could fill an important information gap with the potential to be a cost-effective initial database source to guide human factors efforts to improve care quality, reduce errors, and increase patient safety.

[Outcome of treatment with peg-interferon and ribavirin in HIV-HCV co-infected patients: "real life" single center experience].

BACKGROUND AND AIM: Recently, with the emergence of highly effective antiretroviral treatment (ART), chronic liver disease has become the leading cause of morbidity and mortality in co-infected HIV-HCV (Human immunodeficiency virus-Hepatitis C virus) patients. The overall SVR rate in this population remains unsatisfactory. The aim of this study was to evaluate the response to therapy in HIV-HCV co-infected patients in a single center. PATIENTS AND METHODS: Consecutive HIV-HCV co-infected patients were evaluated in the liver clinic between 2003 -2010. Liver needle biopsy was conducted in 100% of the patients. The patients were treated by a multidisciplinary team consisting of immunologists, hepatologists, social workers and nurses and a close follow-up was conducted. The 48 weeks duration of peg-interferon and ribavirin combination was used for all genotypes according to recent guidelines. Weight-adjusted ribavirin doses were applied. Treatment was initiated after stabilization of HIV parameters and successful weaning from drug and alcohol addiction. RESULTS: A total of 86 out of 143 HIV- HCV co-infected patients, were evaluated; 39 completed treatment. Of those 31 (77%) achieved SVR. Out of 22 genotype 1 patients, 18 (82%) achieved SVR. Six patients had spontaneous viral clearance and 8 are still receiving treatment. In 17 non-one genotype patients, the SVR rate was 76.4% (13 of 17 patients); 6 patients were defined as relapsers and non-responders. Overall adherence to the treatment was high. CONCLUSION: Measures, such as the use of a multidisciplinary approach, high adherence of physicians to the guidelines, weight-based ribavirin dose, and selecting patients who are ready to start therapy, can significantly improve the SVR rate in this difficult-to-treat patient population.

Accelerated Aging in HIV Patients.

Life expectancy has been increasing in the last few decades in the Western world and is accompanied by higher occurrence of age-related diseases like metabolic, cardiovascular, and renal diseases and also with a decline in immune functions. In HIV-infected people, due to the use of combination antiretroviral therapy (cART), life expectancy has increased. As a result, non-AIDS conditions which are age-associated have become more prevalent and appear earlier, resulting in accelerated aging in HIV patients. These non-AIDS conditions in HIV patients are associated with CD4+ T cell counts: lower counts are associated with higher rates of liver, cardiovascular, renal, and neurocognitive disorders. The effect of viral load and cART on the earlier occurrence of age-associated diseases is less significant than the CD4 count effect. Thus, the loss of immune functions in HIV-infected patients may enhance aging.

Absence of APOL1 risk variants protects against HIV-associated nephropathy in the Ethiopian population.

BACKGROUND: Susceptibility to end-stage kidney disease (ESKD) among HIV-infected Americans of African ancestral heritage has been attributed to APOL1 genetic variation. We determined the frequency of the APOL1 G1 and G2 risk variants together with the prevalence of HIV-associated nephropathy (HIVAN) among individuals of Ethiopian ancestry to determine whether the kidney disease genetic risk is PanAfrican or restricted to West Africa, and can explain the previously reported low risk of HIVAN among Ethiopians. METHODS: We studied a cohort of 338 HIV-infected individuals of Ethiopian ancestry treated in one Israeli and one Ethiopian center. We sought clinical evidence for HIVAN (serum creatinine >1.4 mg/dl or proteinuria >30 mg/dl in a spot urine sample). Genetic analyses included the genotyping of the APOL1 G1 and G2 variants, and a panel of 33 genomic ancestry-informative markers. Statistical analysis compared clinical and genetic indices for HIV-infected individuals of Ethiopian ancestry and overall Ethiopians to those reported for HIV-infected African-Americans, overall African-Americans, West Africans and non-Africans. FINDINGS: Three (0.8%) of 338 HIV-infected patients of Ethiopian ancestry showed clinical criteria compatible with renal impairment. Two of these 3 patients also have severe poorly controlled diabetes mellitus. The third nondiabetic patient underwent renal biopsy which ruled out HIVAN. This absence of clinically apparent HIVAN was significantly different from that reported for African-Americans. The APOL1 G1 and G2 risk variants were found, respectively, in 0 and 2 (heterozygote state) of the 338 HIV-infected individuals. Global ancestry and the frequencies of the APOL1 G1 and G2 variants are not statistically different from their frequencies in the general Ethiopian population, but are significantly and dramatically lower than those observed among HIV-infected African-Americans, African-Americans and West Africans. INTERPRETATION: The coinciding absence of HIVAN and the APOL1 risk variants among HIV-infected individuals of Ethiopian ancestry support a Western rather than Pan-African ancestry risk for ESKD, and can readily explain the lack of HIVAN among individuals of Ethiopian ancestry.

Men who have sex with men, risk behavior, and HIV infection: integrative analysis of clinical, epidemiological, and laboratory databases.

BACKGROUND: Centralized data collection and analytic tools facilitate tracing HIV transmission trends at the patient-population level with increasing resolution, complementing behavioral studies while avoiding sampling biases. By several measures, the rate of HIV infection among men who have sex with men (MSM) in Israel increased in the past several years more rapidly than was expected. We describe features of the data that connect this increase to behavioral changes. METHODS: We retrospectively analyzed data from the national HIV reference laboratory and the national HIV and sexually transmitted infections registries. We examined changes in selected epidemiologic and clinical parameters and in the pattern of drug-resistant virus transmission among MSM in Israel. In particular, virus isolates from 296 MSM (23.8% of all MSM who received a diagnosis) were genotyped, drug-resistance conferring mutations were characterized, and phylogenetic trees were constructed. RESULTS: Compared with earlier years, during 2007-2009 MSM were more often infected with drug-resistant virus before treatment initiation, were coinfected with syphilis, and received a diagnosis during acute retroviral syndrome. Phylogenetic analysis suggested frequent transmission of drug-resistant HIV by drug-treated individuals to >1 partner. Secondary transmission of resistant virus by drug-naive patients is also consistent with the phylogenetic patterns. In addition, non-B HIV subtypes began to appear among MSM. CONCLUSIONS: Together, our findings suggest that the sexual behavior of MSM, both HIV-infected and uninfected, has become riskier, contributing to the number of those seeking early clarification of status, to syphilis comorbidity, and to the spread of drug resistance. These findings call for action by public health planners and community-based organizations aimed at increasing awareness of the risks, bringing a change in attitude and establishing safe sex norms.

Cell derived liposomes expressing CCR5 as a new targeted drug-delivery system for HIV infected cells.

Anti-retroviral-therapies against HIV/AIDS focus on inhibiting viral growth and may slow AIDS progression, but not cure the disease. Here we describe an approach to treat HIV as a cellular pathology by targeting cell derived liposomes against HIV-infected cells. Cell-derived-liposomes were prepared from the cytoplasmatic membranes of cells expressing CCR5, the human receptor for gp120, that is found on the surface of virions and HIV-infected cells. The specific targeting and cytotoxicity of the cell-derived liposomes towards gp120-expressing cells were studied. Cell-derived liposomes exhibited unilamellar morphology and were found to be of 100-200 nm in diameter. Moreover, CCR5 that was expressed on the surface of the cell-derived liposomes was biologically active and correctly oriented. Cell-derived liposomes incubated with HIV-infected model cells exhibited significant and specific targeting to those gp120-expressing cells. To demonstrate the system efficacy, EDTA was selected as liposomal encapsulate and was shown to cause high cytotoxic effect when introduced into the cell cytoplasm. Finally, cell-derived liposomes containing EDTA led to a 60% reduction in the viability of gp120-expressing cells compared to no effect on control cells that do not express gp120. These results demonstrate the specific targeting and cytotoxic effect of CCR5-conjugated cell-derived liposomes towards gp120-expressing HIV model cells, suggesting for a potential new therapeutic approach.

Cytokine levels as potential biomarkers for predicting the development of posttraumatic stress symptoms in casualties of accidents.

BACKGROUND: Traumatic injuries are usually associated with increased secretion of pro-inflammatory cytokines, and are sometimes followed by the development of acute stress symptoms (ASS) and posttraumatic stress symptoms (PTSS). AIMS: To measure serum pro- and anti-inflammatory cytokines in accident casualties and to associate it with ASS at hospitalization, and with PTSS 1 month later. METHODS: Participants were 48 patients, aged 20-60, hospitalized following various orthopedic injuries including bone fractures, and 13 healthy volunteers matched for gender. At hospitalization (Time 1), 30 ml heparinized venous blood were drawn and cytokines levels in serum were assessed; participants filled out the Acute Stress Disorder Inventory (ASDI), COPE, and injury-related questionnaires. One month later (Time 2), 26 participants filled out the Posttraumatic Disorder Symptom Scale (PDS). RESULTS: High serum levels of IL-6, IL-8, and TGF-beta and low levels of serum IL-4 and IL-10 were found in injured patients as compared with controls, When controlling for age and severity of injury in the regression analysis, higher levels of IL-6 and IL-8 and lower TGF-beta were predicted by higher ASS and higher use of and emotion-focused coping. Higher PTSS scores at Time 2 were predicted by higher levels of IL-8, lower levels of TGF-beta, and higher ASS measured at Time 1. CONCLUSIONS: High levels of the pro-inflammatory cytokine IL-6 and IL-8 and lower levels of the regulatory cytokine TGF-beta should be further assessed as a possible risk factor or a bio-marker of PTSS in accident casualties.

Iatrogenic Cushing's syndrome due to coadministration of ritonavir and inhaled budesonide in an asthmatic human immunodeficiency virus infected patient.

INTRODUCTION: Iatrogenic Cushing's syndrome (CS) is caused by exposure to glucocorticoids and may be promoted by interaction with additional drugs. It is well known in asthmatic human immunodeficiency virus (HIV)-infected patients treated with inhaled fluticasone with ritonavir-containing antiretroviral regimen (cART). CASE REPORT: The authors present an asthmatic HIV-infected Ethiopian woman, treated with fluticasone/salmeterol, commencing cART with tenofovir, emtricitabine, and lopinavir/ritonavir. During 7 months she gained 9 kg and hyperpigmentation, mild edema, marked abdominal striae, and increase in blood pressure were noted. Plasma am and urine free cortisol levels confirmed CS diagnosis and fluticasone was discontinued. Complete resolution of CS occurred within 2 months. However, frequent asthma symptoms required resumption of inhaled corticosteroid (ICS) treatment, and budesonide/formeterol was prescribed. Soon reemergence of symptomatic CS was noted. Ritonavir dose was halved, but CS symptoms continued to develop. Budesonide was stopped and montelukast initiated. Resolution of cushingoid symptoms was observed within weeks. DISCUSSION: Corticosteroids are metabolized by cytochrome P450 3A4 (CYP3A4). Fluticasone has the longest glucocorticoid receptor-binding half-life and is 300 times more lipophilic than budesonide. Inhaled fluticasone possesses a high suppression rate of hypothalamic-pituitary-adrenal axis. Ritonavir, a potent CYP3A4 inhibitor, may inhibit corticosteroid degradation and increase its accumulation. Inhaled budesonide is less likely to cause adrenal suppression. Diagnosing Cushing's syndrome presents a clinical challenge due to similarities with clinical manifestations and side effects related to cART. In patients treated with inhaled or intranasal corticosteroids together with cART there may be a higher incidence of iatrogenic CS. CS should be looked for, and management considered carefully.