Mechanisms of peripheral microvascular dysfunction in transgenic mice overexpressing the Alzheimer's disease amyloid Abeta protein

Freshly prepared soluble amyloid (Abeta) peptide has been reported to have vascular actions both in vitro and in vivo. This study was designed to examine the in vivo microvascular effects of beta in two skin microvascular model systems that might reflect possible short and long-term vascular effects of this peptide. Short-term vascular effects were examined using freshly prepared soluble Abeta(1-40) peptide superfused over naive rat skin microvasculature for 15 min. Peripheral microvascular functional changes in 9-months-old transgenic (Tg) mice overexpressing soluble beta in the brain, peripheral circulation and other tissues, were also examined. Microvascular responses were monitored using laser Doppler flowmetry from the base of a blister raised on the hind footpad of the animals. Endothelial-dependent and independent vasodilatation responses (VD) were examined using acetylcholine (ACh) and sodium nitroprusside (SNP) respectively. The exposure of na?ve rat skin microvasculature to Abeta(1-40) resulted in an immediate vasoconstriction (VC) that prevented ACh but not SNP from inducing a subsequent VD response. The vascular effects of Abeta(1-40) were reversed by antioxidants (superoxide dismutase and catalase) and an endothelin A (ETA) receptor antagonist (BQ-123). Tg mice overexpressing soluble Abeta and C100 showed significant reductions in both endothelial-dependent and endothelial-independent VD that were also reversed by antioxidants and BQ-123. In conclusion, this study provided evidence to support the notion of peripheral vascular effects of Abeta in vivo and present novel evidence for alterations in endothelial and smooth muscle cell function in peripheral skin microvasculature in Tg mice overexpressing Abeta and C100. We suggest that skin microvasculature is a useful model to examine the mechanisms underlying the vascular actions of the Abeta protein.     

Pediatric invasive fungal rhinosinusitis in immunocompromised children with cancer.

OBJECTIVES: 1) To determine the factors that predispose towards invasive fungal rhinosinusitis (FS) in immunocompromised children with cancer, and 2) to propose practice guidelines for management of pediatric FS in immunocompromised patients. METHODS: Retrospective chart review of 9 patients who developed invasive FS compared to 8 patients who did not develop invasive FS during the study period. Presenting signs and symptoms, nasal endoscopic findings, radiographs, laboratory studies, histologic and microscopic samples, and outcomes were compared. RESULTS: Seventeen consecutive pediatric immunocompromised patients with hematologic and lymphoid neoplasms underwent nasal endoscopy and biopsy for possible FS. Nine patients were diagnosed with 10 episodes of FS; 1 patient developed FS with different organisms on 2 separate occasions separated by 6 months; 8 patients were not diagnosed with FS. Eight patients had acute myelogenous leukemia (AML); 6 patients had acute lymphoblastic leukemia (ALL); 1 patient had Burkitt's lymphoma, 1 patient had undifferentiated leukemia; and 1 patient had biphenotypic acute leukemia. All patients with FS had an absolute neutrophil count (ANC) 600 or less (range 0-600). All patients with FS had either persistent fevers or sinus symptoms (facial pain, nasal congestion, rhinorrhea). Sinus CT scans were abnormal in all patients with FS and without FS. Two patients with FS had maxillary sinus retention cysts. Operative endoscopic findings were helpful diagnostically when necrosis or ulceration was found. All patients in the non-FS group normalized their ANCs; 2 of the 9 patients in the FS group did not normalize their ANC. These 2 patients died from disseminated FS or from complications due to their immunosuppression. CONCLUSION/SIGNIFICANCE: All patients with FS had either persistent fevers or symptoms localized to the sinuses (facial pain, nasal congestion, or rhinorrhea). Endoscopic examination was helpful when necrosis was detected. We recommend directed biopsies of suspicious lesions, the middle and inferior turbinate, in immunocompromised, neutropenic pediatric patients with cancer who present with either persistent fevers or localizing symptoms to the sinuses. We favor the use of "rush" biopsies over frozen sections because of the better-quality sections and ability to perform appropriate stains.     

Aggregation and activation of blood platelets in exercise and training

This article presents an overview of the progress that has been made in recent years in our understanding of the interaction between exercise and platelets in health and disease. Although platelets are important in normal haemostasis, recent evidence emphasises the pivotal role of abnormal platelet function in acute coronary artery diseases, myocardial infarction, unstable angina and stroke. In light of the positive health benefits of exercise, interest has been heightened on the association between exercise and platelet aggregation and function, not only in normal healthy subjects but also in patients. However, the study of exercise effects on blood platelets are highly contentious because of the fact that the analytical methods employed to study platelets are bedevilled by numerous methodological problems. While exercise effects on platelet aggregation and function in healthy individuals have been extensively examined, the evidence reported has been conflicting. Somewhat less contradictory are the results generated from studies in patients with coronary heart disease, as the preponderance of evidence available would strongly suggest that platelet aggregation and function are increased with exercise. Several drugs are known to influence platelet aggregation and function, the most examined among these medications is aspirin (acetylsalicylic acid). However, aspirin appears to be ineffective to attenuate exercise-induced increases in platelet aggregation and activation. Few studies are available on the effect of training on blood platelets and the exact effects of exercise training on platelet activation and function is not as yet known. This lack of information makes further studies particularly important, in order to clarify whether there are favourable effects of exercise training on platelet aggregation and function in health and disease.     

Effects of diabetes on creatine kinase activity in streptozotocin-diabetic rats

OBJECTIVE To study the effect of diabetes on the creatine kinase (CK) activity in different tissues of streptozotocin-induced diabetic rats.

METHODS Serum samples, heart, extensor digitorum longus, brain and bladder were collected from both streptozotocin-induced diabetic rat and control group. Ck was measured by enzymologic method.

RESULTS The body weight, heart weight and brain weight were reduced significantly compared with control group (P < 0.001), but bladder weight was increased significantly (P < 0.001). CK activity in serum and extensor digitorum longus in diabetic rat was significantly lower (P < 0.001); CK activity in diabetic heart was lower (P < 0.01); and in brain also lower (P < 0.05). A higher CK activity in diabetic bladder was found (P < 0.001).

CONCLUSIONS Diabetes can result in a lower CK activity in serum, heart, brain and extensor digitorum longus that may affect the energy metabolism in the tissues. A higher CK activity in diabetic bladder may reflect a functional compensatory mechanism.

     

Comparison between molecular epidemiology, geographical regions and drug resistance in Mycobacterium tuberculosis strains isolated from Iranian and Afghan patients

The aim of this study was to determine the prevalence of drug-resistant tuberculosis (TB) and its associated risk factors. The susceptibilities of Mycobacterium tuberculosis isolates were tested against four first-line antituberculous drugs and were typed by spoligotyping. Spoligotyping of M. tuberculosis strains resulted in 95 different patterns that were divided into three evolutionary groups (1-3). Eighty-six (90%) of the isolates had unique patterns that were reported for the first time. Interestingly, 9.4% of the strains belonged to the Beijing family. Multidrug resistance (MDR) was seen in group 1 of the evolutionary scenario. All M. tuberculosis isolates belonging to the Beijing family were associated with a resistance pattern. MDR was much higher in bacteria isolated from Afghan TB patients residing in Iran.     

Left ventricular function and left atrial volumes in rheumatoid arthritis patients: Subclinical cardiac involvement and relation to seropositivity

BackgroundLeft ventricular (LV) dyfunction with preserved ejection fraction has been associated with increased mortality. Left atrium (LA) modulates LV filling and plays a role in maintaining cardiac function. Cardiovascular disease is a leading cause of death in rheumatoid arthritis (RA).Aim of the workTo study the left atrium modulating the left ventricular filling and to investigate its relation with disease activity to detect subclinical early cardiac affection in RA patients.Patients and methods45 RA patients and 30 control were studied. The disease activity score (DAS28) was calculated. Conventional and tissue Doppler imaging (TDI) and strain (S) and strain rate (SR) analysis by two-dimensional speckle tracking of LA were conducted.ResultsThe 45 female patients mean age was 38.8 ± 8.7 years, disease duration was 7.3 ± 6.2 years and mean DAS28 was 4.1 ± 0.9. Regarding the LA emptying fractions, only the 2 LA passive emptying fraction (PEF) and total emptying fraction (TEF) were significantly lower in patients compared to control (p = 0.01 and p = 0.025 respectively). The LA expansion index (EI) was significantly reduced in patients compared to control (p = 0.009). Regarding TDI-derived mitral annular velocities, lateral e’ and s as well as SRe (l/s) were significantly slower in patients compared to control (p = 0.001, p = 0.02 and p < 0.0001 respectively). Rheumatoid factor (RF) was significantly inversely related to TDI laterale, TDI laterals, and strain rate e, LA-PEF, LA-EI and LA-TEF.ConclusionRA patients had alteration in LV longitudinal myocardial function and more LA stiffness. Cardiac affection is more in seropositive patients.     

Brominated Flame Retardants in Fish of Lake Geneva (Switzerland)

Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) were determined in fish (Salmo trutta forma lacustris) from Lake Geneva. Brominated flame retardants were detected in all nine samples with an average concentration for the sum of BDE-28, BDE-47, BDE-49, BDE-66, BDE-99, BDE-100, BDE-119, BDE-153, BDE-154 and BDE-209 of 207 ng per g lipid weight (ng g lw⁻¹). The congener patterns were dominated by BDE-47. The average concentration of HBCD was 168 ng g lw⁻¹.     

Topical Tranexamic Acid Compared With Anterior Nasal Packing for Treatment of Epistaxis in Patients Taking Antiplatelet Drugs: Randomized Controlled Trial

Objective

We evaluated the efficacy of topical application of the injectable form of tranexamic acid (TXA) compared with anterior nasal packing (ANP) for the treatment of epistaxis in patients taking antiplatelet drugs (aspirin, clopidogrel, or both) who presented to the emergency department (ED).

Methods

A randomized, parallel‐group clinical trial was conducted at two EDs. A total of 124 participants were randomized to receive topical TXA (500 mg in 5 mL) or ANP, 62 patients per group. The primary outcome was the proportion of patients in each group whose bleeding had stopped at 10 minutes. Secondary outcomes were the rebleeding rate at 24 hours and 1 week, ED length of stay (LOS), and patient satisfaction.

Results

Within 10 minutes of treatment, bleeding was stopped in 73% of the patients in the TXA group, compared with 29% in the ANP group (difference = 44%, 95% confidence interval, 26% to 57%; p < 0.001). Additionally, rebleeding was reported in 5 and 10% of patients during the first 24 hours in the TXA and the ANP groups, respectively. At 1 week, 5% of patients in the TXA group and 21% of patients in the ANP group had experienced recurrent bleeding (p = 0.007). Patients in the TXA group reported higher satisfaction scores (median [interquartile range {IQR}], 9 [8–9.25]) compared with the ANP group (median [IQR] = 4 [3–5]; p < 0.001). Discharge from the ED in <2 hours was achieved in 97% of patients in the TXA group versus 13% in the ANP group (p < 0.001). There were no adverse events reported in either group.

Conclusions

In our study population, epistaxis treatment with topical application of TXA resulted in faster bleeding cessation, less rebleeding at 1 week, shorter ED LOS, and higher patient satisfaction compared with ANP.