Angiotensin-(1–7) stimulates hematopoietic progenitor cells in vitro and in vivo

Effects of angiotensin (Ang)-(1–7), an AngII metabolite, on bone marrow-derived hematopoietic cells were studied. We identified Ang-(1–7) to stimulate proliferation of human CD34⁺ and mononuclear cells in vitro. Under in vivo conditions, we monitored proliferation and differentiation of human cord blood mononuclear cells in NOD/SCID mice. Ang-(1–7) stimulated differentially human cells in bone marrow and accumulated them in the spleen. The number of HLA-I⁺ and CD34⁺ cells in the bone marrow was increased 42-fold and 600-fold, respectively. These results indicate a decisive impact of Ang-(1–7) on hematopoiesis and its promising therapeutic potential in diseases requiring progenitor stimulation.     

Changes in Chemosensitivity and Mechanosensitivity in Aging and Parkinson’s Disease

The risk of aspiration pneumonia in Parkinson’s disease (PD) may be increased by sensory loss in the laryngopharynx and a reduced cough reflex. This study investigated changes in chemo- and mechanosensation with age and in PD and documented cough thresholds and cortical influences over cough. Single-breath citric acid inhalation cough challenge and flexible nasendoscopy were performed in 32 participants with idiopathic PD (mean age = 68.5 years, range = 45.8–82.5) and 16 healthy young adults (8 males, mean age = 25.1 years, range = 21.3–32.4), and 16 healthy elders (8 males, mean age = 72.8 years, range = 61.5–84.7) as controls. Individuals with PD had reduced sensation at the base of the tongue compared to age- and gender-matched counterparts (p < 0.005). All groups demonstrated lower natural cough thresholds than suppressed cough thresholds. No differences in natural cough thresholds were found across groups. Young adults demonstrated greater ability to suppress cough compared to healthy elders (p = 0.021). Tongue-base mechanosensory impairment in PD may account for vallecular residue and complaints of globus sensation. However, decreased cough response was not found to be a characteristic of PD. This study provided evidence for voluntary control of cough and the lack of decline of chemosensitivity with age or disease.     

Comparison of a Novel Liquid (Adcon-P®) and a Sodium Hyaluronate and Carboxymethylcellulose Membrane (Seprafilm™) in Postsurgical Adhesion Formation in a Murine Model

PURPOSE: Intra-abdominal administration of antiadhesive barriers may reduce the extent and severity of postoperative adhesions. This study aimed to compare the effectiveness of a novel liquid antiadhesive barrier with a conventional sheet (Seprafilm) antiadhesive barrier in a murine cecal abrasion model. METHODS: One hundred fifty Swiss-Wister mice underwent laparotomy and cecal abrasion and were randomly assigned to receive Adcon-P (n = 30) or Seprafilm (n = 30) or to a control group (n = 90). At postoperative Day 21, the mice underwent relaparotomy and complete adhesiolysis. An investigator who was blinded to the group assignment scored the extent of adhesion formation and the difficulty of adhesiolysis using a 6-point scale that ranged from 0 (no adhesions) to 5 (full-thickness intestinal injury with adhesiolysis). Results are reported as median (range). RESULTS: Median adhesion scores in mice receiving Adcon-P (0 (range, 0-1)) and Seprafilm (1 (range, 0-3)) were lower than in mice in the control group (2 (range, 0-5); P < 0.0001 for both comparisons). In addition, the median adhesion score for the Adcon-P group was significantly lower than that of the Seprafilm group (P = 0.02). CONCLUSION: This study suggests that both Adcon-P and Seprafilm trade mark decrease the incidence of postoperative adhesions and the difficulty of adhesiolysis in the murine cecal abrasion model. However, Adcon-P appeared to be superior to Seprafilm. This agent is an attractive device that requires additional studies.     

IL-17 and Regulatory Cytokines (IL-10 and IL-27) in L. braziliensis Infection

Cutaneous leishmaniasis (CL) is characterized by high production of pro‐inflammatory cytokines and development of pathology. Individuals with subclinical L. braziliensis infection (SC) have a positive skin test to leishmania, but do not develop disease. We evaluated whether the downregulation of inflammatory response in SC is mediated by IL‐10 and IL‐27 and whether IL‐17 is associated with control of infection. Participants include SC individuals, patients with CL and healthy subjects. Cytokines protein and mRNA were detected by ELISA and real‐time PCR. IFN‐γ and TNF‐α levels were higher in CL than in SC group. The IL‐10 levels and mRNA for IL‐10 were similar in both SC and CL. mRNA for IL‐27 was increased in cells from SC after stimulation with L. braziliensis antigen. There was a tendency for increased levels of IL‐17 in SC compared to CL. The weak type 1 immune response observed in SC L. braziliensis infection is not because of the regulatory effects of IL‐10 and IL‐27. The control of Leishmania infection may be mediated by innate immune response with participation of IL‐17. The results from this pilot study warrant further larger studies to investigate the potential contributions of IL‐17 and IL‐27 to the control of L. braziliensis infection.     

Enzyme linked immunosorbent assay (ELISA) in diagnosis and evaluation of therapeutic effect in schistosomiasis.

With the serum titer of 1: 32, the mean OD value (0.981±0.379) of antibodypositive reaction read spectrophotometrically in schistosomiasis patients was significantlyhigher than that (0.230±0.111) in residents of endemic area under control and in     

TNF-α and plasma D(-)-lactate levels in rats after intestinal ischemia and reperfusion

Objective To study the potential role of tumor necrosis factor-or(TNF-α)induction in the development ofmucosal barrier dysfunction in rats caused by acute intestinal ischemia-reperfusion injury,and to examine whetherpretreatment with monoclonal antibody against TNF-α(TNF-αMoAb)would affect the release of D(-)-lactate afterlocal gut ischemia followed by reperfusion.Methods Anesthetized Sprague-Dawley rats underwent superiormesenteric artery occlusion for 75 min followed by reperfusion for 6 hr.The rats were treated intravenonsly with eitherTNF-α MoAb(20 mg/kg)or albumin(20 mg/kg)30 min prior to the onset of ischemia.Plasma D(-)-lactate levelswere measured in both the portal and systemic blood by an enzymatic spectrophotometrie assay.Intestinal TNF-αmRNA expression as well as protein levels were also measured at various intervals.In addition,a postmortemexamination was performed together with a macropatholngical evaluation based on a four-grade scoring system.Results Intestinal ischemia resulted in a significant elevation in D(-)-lactate levels in the portal vein blood in boththe control and treatment groups(P<0.05).However,animals pretreated with TNF-α MoAb at 6 hr after reperfusionshowed significant attenuation of an increase in both portal and systemic D(-)-lactate levels when compared with thoseonly receiving albumin(P<0.05).In the control animals,a remarkable rise in intestinal TNF-α level was measuredat 0.5 hr after clamp release(P<0.01);however,prophylactic treatment with TNF-α MoAb completely annulled theincrease of local TNF-α levels seen in the control animals.Similarly,after anti-TNF-α MoAb administration,intestinalTNF-α mRNA expression was markedly inhibited,which showed significant differences when compared with the controlgroup at 0.5 hr,2 hr and 6 hr after the release of occlusion(P<0.05-0.01).In addition,the pathologicalexamination showed marked intestinal lesions that formed during ischemia,which were much worse upon reperfusion,particularly at the 6 hr time point.These acute injuries were obviously attenuated in animals receiving TNF-α MoAb.Conclusions It appeared that acute intestinal ischemia was associated with failure of the mucosal barrier,resulting inincreased plasma D(-)-lactate levels in both portal and systemic blood.These results suggest that TNF-α appears to beinvolved in the development of local damage associated with intestinal ischemic injury.Moreover,prophylactictreatment with TNF-α MoAb exerts preventive effects on ischemia/reperfusion-induced circulating D(-)-lactateelevation and gut injury.(J Geriatr Cardiol 2004;1(2):119-124.)     

FibroSURE~(TM) and FibroScan~ in relation to treatment response in chronic hepatitis C virus

AIM:To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus(HCV)cohort.METHODS:Patients with chronic HCV were randomized to receive interferon-based therapy for 24(genotypes 2/3)or 48(genotype 1)wk.FibroSURE～TM(FS)was assessed at baseline and at week-12 post-treatment follow-up.Baseline biopsy for METAVIR was assessed by a single pathologist.FibroScan～ transient elastogra-phy(TE)was performed during treatment in a patient subset.R...     

Intimate Partner Violence (IPV) and Associated Factors in HPTN 071 (PopART) Study Communities in Zambia and South Africa—A Comparison by HIV Status

AIDS and Behavior - The HPTN 071(PopART) study was a community-randomised trial in Zambia and South Africa, examining the impact of combination-prevention including universal testing and treatment...     

Effect of Sanguis draconis (a dragon's blood resin) on streptozotocin- and cytokine-induced β-cell damage, in vitro and in vivo

The study was to examine the effects of Sanguis draconis ethanol extract (SDEE) on streptozotocin (STZ)- and cytokine-induced β-cell damage. In vitro, SDEE did not cause cytotoxicity below 200 μg/ml, and can prevent STZ (5 mM)-induced cell death and apoptosis below 100 μg/ml on RIN-m5F cells. SDEE inhibits IL-1β/IFN-γ-stimulated NO, TNF-α release, and iNOS expression. Furthermore, SDEE suppressed the IL-1β/IFN-γ- or STZ-induced p65 expression of NF-κB, which is associated with inhibition of IκB-α degradation. In vivo, treatment of ICR mice with STZ (100 mg/kg, i.p. single injection) resulted in hyperglycemia and hypoinsulinemia, which was further evidenced by blood glucose and plasma insulin. The diabetogenic effects of STZ were completely prevented when mice were orally administered with SDEE for 3 weeks, however, the blood glucose and plasma insulin showed no significant change after SDEE administration alone. In addition, SDEE also can inhibit STZ-induced iNOS protein expression, pancreatic injury and lipid peroxidation. In conclusions, the molecular mechanism by which SDEE inhibits iNOS gene expression appears to involve the inhibition of NF-κB activation. These results suggest the possible therapeutic value of S. draconis and could be potentially developed into a novel drug for preventing the progression of diabetes mellitus.     

Crohn’s and colitis in children and adolescents

Crohn’s disease and ulcerative colitis can be grouped as the inflammatory bowel diseases (IBD). These conditions have become increasingly common in recent years, including in children and young people. Although much is known about aspects of the pathogenesis of these diseases, the precise aetiology is not yet understood, and there remains no cure. Recent data has illustrated the importance of a number of genes-several of these are important in the onset of IBD in early life, including in infancy. Pain, diarrhoea and weight loss are typical symptoms of paediatric Crohn’s disease whereas bloody diarrhoea is more typical of colitis in children. However, atypical symptoms may occur in both conditions: these include isolated impairment of linear growth or presentation with extra-intestinal manifestations such as erythema nodosum. Growth and nutrition are commonly compromised at diagnosis in both Crohn’s disease and colitis. Consideration of possible IBD and completion of appropriate investigations are essential to ensure prompt diagnosis, thereby avoiding the consequences of diagnostic delay. Patterns of disease including location and progression of IBD in childhood differ substantially from adult-onset disease. Various treatment options are available for children and adolescents with IBD. Exclusive enteral nutrition plays a central role in the induction of remission of active Crohn’s disease. Medical and surgical therapies need to considered within the context of a growing and developing child. The overall management of these chronic conditions in children should include multi-disciplinary expertise, with focus upon maintaining control of gut inflammation, optimising nutrition, growth and quality of life, whilst preventing disease or treatment-related complications.     

Assessment of resin perfusion in hepatic failure in vitro and in vivo

AIM:To observe the adsorbent effect of resin on endotoxin,cytokine,bilirubin in plasma of patients with hepatic failureand to determine the resin perfusion as an artificial liversupport system in the treatment of hepatic failure.METHODS:One thousand milliliters of discarded plasmawas collected from each of 6 severe hepatitis patients treatedwith plasma exchange.The plasma was passed through aresin perfusion equipment for 1-2 h via extracorporealcirculation,and then absorbent indicators of transaminase,bilirubin,blood ammonia,endotoxin and cytokines wereexamined.In the meantime,study of in vivo resin plasmaperfusion was performed on 7 severe hepatitis patients tocompare the changes of endotoxin and cytokines in bloodbefore and after perfusion.RESULTS:The levels of total bilirubin,endotoxin,interleukin1β and TNF-α in plasma were significantly decreased afterin vitro resin plasma perfusion.The levels of interleukin 1β,TNF-α and endotoxin in blood were also evidently declinedafter in vivo resin plasma perfusion.Nevertheless,no obviouschanges in IL-6,creatinine (Cr) and urea nitrogen (UN),bloodammonia and electrolytes were found both in vitroand in vivo.CONCLUSION:Bilirubin,endotoxin and cytokines in plasmaof patients with hepatic failure can be effectively adsorbedby resin in vitro.Most cytokines and endotoxin in plasma canalso be effectively removed by resin in vivo.It demonstratesthat resin perfusion may have good treatment efficacy onhepatic failure and can be expected to slow down theprogression of hepatic failure.     

Tear and saliva ferning tests in Sjögren's Syndrome (SS)

Summary The purpose of this study was to evaluate the tear ferning test (TFT) and the saliva ferning test (SFT) as diagnostic tests for xerophthalmia and xerostomia respectively in patients with SS. Dried samples of freshly produced tears and saliva from: (A) 36 healthy controls without sicca symptoms, (B) 61 patients with primary SS, (C) 53 patients with secondary SS and (D) 22 patients with psychiatric disorders receiving antidepressants, were examined by polarizing light microscopy. All individuals included in the study were postmenopausal women. The crystallization was classified into 4 types according to the ferning phenomenon: uniformity, branching, spreading and integrity (type I normal and II, III, IV abnormal). Abnormal TFT was found in tear samples of: (A) 8/72 normal control eyes, (B) 110/122 prim SS eyes, (C) 86/106 sec SS eyes and (D) 30/44 psychiatric patients' eyes. Abnormal SFT was found in: (A) 6/36 of normal controls, (B) 59/61 of prim SS, (C) 51/53 of sec SS patients and (D) 16/22 of psychiatric patients. The differences of both TFT and SFT of patients with prim SS and sec SS versus controls were significant (p<0.001). The sensitivity of TFT was found to be high both in prim SS (90%) and in sec SS (81%). In addition the specificities of TFT and SFT were high 89% and 83% respectively. On the other hand the differences of TFT and SFT in psychiatric patients receiving antidepressants versus normal controls were also significant (p<0.05 and p<0.025 respectively). According to our data TFT and SFT are simple, sensitive and specific tests to evaluate xerophthalmia and xerostomia in SS and probably in other conditions characterized by mucous membrane dryness.     

Terbutaline in COPD comparison between turbuhaler® and chlorofluorocarbon (CFC) inhaler

Patients with chronic obstructive pulmonary disease (COPD) often subjectively benefit from inhaled R2-agonists in spite of little or no demonstrable effect in forced expiratory volume in 1 second (FEV_1.0). A comparison between the effects of terbutaline administered via a dry powder inhaler (Turbuhaler®) and via a chlorofluorocarbon (CFC) inhaler in conjunction with a spacer device (Nebuhaler®) was performed in patients with regard to FEV_1.0, forced expiratory capacity (FVC), residual volume (RV), and specific conductance (s-Gaw). Fifteen hospitalised patients (11 male) with COPD were studied, each of whom had a diurnal variation in peak expiratory flow (PEF) not exceeding 15% and with a demonstrated volume response to inhaled ₂-agonists in FVC and/or RV of at least 15%. Patients were administered each of the following five treatments on a single occasion in a randomized order (latin square) in intervals of at least 2 days: placebo, terbutaline via Turbuhaler (1.0 and 2.5 mg) and terbutaline via a CFC inhaler (1.0 mg without and 2.5 mg with Nebuhaler). Inhalation of terbutaline in different doses and from different devices induced a decrease in RV, an increase in FVC, and s-Gaw and a less pronounced increase in FEV_1.0. No statistically significant differences between the four terbutaline treatments were seen, but all were significantly different from the placebo. These findings indicate that while patients with COPD may benefit from inhaled terbutaline through decreased hyperinflation, the choice of inhalation device seems to be of little importance for its efficacy.     

Oxidized LDL and anti-oxidized LDL antibodies in atherosclerosis – Novel insights and future directions in diagnosis and therapy,

We provide an up-to-date overview of current topics surrounding oxidized low-density lipoprotein (oxLDL) and its related antibodies in the quest to better identify the individuals at risk of cardiovascular disease and atherosclerotic plaques with unfavorable characteristics. We discuss the potential of oxLDL and anti-oxLDL antibodies as serum biomarkers of cardiovascular disease and emerging studies examining the targeting of arterial oxLDL for imaging and therapeutic delivery.     

Anti-MCV and anti-CCP antibodies—diagnostic and prognostic value in children with juvenile idiopathic arthritis (JIA)

The goal of the study was to evaluate the diagnostic and prognostic value of anti-mutated citrullinated vimentin (anti-MCV) antibodies in juvenile idiopathic arthritis (JIA) comparing to anti-cyclic citrullinated peptide (anti-CCP). Thirty children with confirmed JIA diagnosis and 20 children as a control group were included into the study. Serum and synovial fluid levels of anti-CCP, anti-MCV, and immunoglobulin M rheumatoid factor (IgM-RF) antibodies have been assessed. Anti-MCV was positive in 11/30 (36.6 %), whereas anti-CCP positivity was found in 12/30 (40 %) children with JIA. Among 11 children with JIA positive for anti-MCV, five (45.5 %) were also positive for anti-CCP and among 18 JIA children negative for anti-CCP, six (33.33 %) were also anti-MCV positive. Six out of 30 JIA children were found to be IgM-RF positive. In general, two out of all those 11 anti-MCV-positive patients demonstrated oligoarthritis and 9/11 had polyarticular type of onset. Anti-MCV serum concentration correlated positively with anti-CCP (p = 0.004). Almost 60 % of children in early stage of JIA were anti-MCV positive. Levels of anti-CCP antibodies correlated positively with the disease activity (p = 0.0014) and radiological outcome (p = 0.00017). In all synovial fluid samples, the concentration of autoantibodies was under the cut-off values. The results of our study indicate that anti-MCV as well as anti-CCP antibodies may be helpful in the diagnosis of JIA, especially in the early course of the disease. Anti-MCV antibodies could identify a group of children with JIA which is negative for anti-CCP antibodies and RF. However, it appears that in JIA, anti-CCP rather than anti-MCV antibodies have impact on radiographic changes.