A novel antibacterial iridoid and triterpene from Caiophora coronata

Bioassay-guided fractionation of the antibacterial CH(2)Cl(2)-MeOH extract obtained from the aerial parts of the Argentinean plant Caiophora coronata led to the isolation of a new triterpene, 1beta,3beta-dihydroxyurs-12-en-27-oic acid, 1, and a new iridoid, 1alpha-methoxy-6alpha,10-dihydroxyisoepiiridomyrmecin (caiophoraenin), 2, along with the known iridoid isoboonein 3. Their structures were established by spectroscopic techniques (1D and 2D NMR, HRFABMS, FTIR). The MIC values of isolated compounds were determined against methicillin-sensitive (MSSA) and -resistant (MRSA) strains of Staphylococcus aureus, Bacillus subtilis (BS), vancomycin-resistant Enterococcus faecium (VREF), Escherichia coli (EC), E. coli imp (ECimp), and Candida albicans (CA). Compound 1 was found active against BS, MSSA, MRSA, VREF, and ECimp with MIC values of 2, 4, 4, 4, and 16 microg/mL, respectively.     

The utility of pallor detecting anemia in under five years old children

The diagnosis and management of anemia, which affects a significant proportion of young children in developing countries, largely depends on the clinical assessment for pallor. This study was conducted with the aim of evaluating the utility of pallor in detecting anemia. Children aged 2 to 60 months who visited the pediatric outpatient department of Jimma Hospital over 3 months period were assessed for the presence and degree of pallor in 4 anatomic sites (conjunctivae, tongue and buccal mucosa, nailbeds, palm) by trained nurses. Hemoglobin was then determined using the HemoCue method. Individuals involved in clinical examination did not have access to the laboratory results before documenting their findings. The mean hemoglobin in the 574 children examined was 11.03 gm/dl, and about 46% had anemia. Children younger than 2 years were found to have a higher prevalence of anemia as compared to older children (p < 0.001). Palmar pallor, with a sensitivity of 58%, had the highest sensitivity to detect moderate anemia as compared to other anatomic sites. The presence of either palmar or conjunctival pallor increased the sensitivity to 73%. The inter-observer agreement was highest for conjunctival pallor (kappa value = 0.81). The findings of the study suggest that pallor of a single anatomic site does not have adequate sensitivity to detect moderate anemia. We recommend further studies to look at the performance of severe pallor in correctly identifying severe anemia. Furthermore, the magnitude and causes of anemia need to be studied in a community setting.     

Increase in tuberculosis incidence among the staff working at the Tuberculosis Demonstration and Training Centre in Addis Ababa, Ethiopia: a retrospective cohort study (1989-1998).

The incidence rate of tuberculosis was studied among the staff of the Tuberculosis Demonstration and Training Centre (TDTC) of Addis Ababa between 1989 and 1998, by reviewing all clinical charts of the 175 staff members for evidence of tuberculosis. During the study period, 24 cases of tuberculosis were diagnosed, including 12 who were bacteriologically confirmed. The incidence rate of tuberculosis increased from 1695 per 100000 person-years (py) in 1989 to 5556/100000 py in 1998 (test for trend, P < 0.001). Urgent measures are required for better protection of the staff from human immunodeficiency virus infection and tuberculosis.     

Renal aquaporin-4 associated pathology in TG-26 mice

Human immunodeficiency virus-associated nephropathy (HIVAN) is a leading cause of end-stage renal disease in HIV patients, which is characterized by glomerulosclerosis and renal tubular dysfunction. Aquaporin-4 (AQP-4) is a membrane bound water channel protein that plays a distinct role in water reabsorption from renal tubular fluid. It has been proven that failure of AQP-4 insertion into the renal tubular membrane leads to renal dysfunction. However, the role of AQP-4 in HIVAN is unclear. We hypothesize that impaired water reabsorption leads to renal injury in HIVAN, where AQP-4 plays a crucial role. Renal function is assessed by urinary protein and serum blood urea nitrogen (BUN). Kidneys from HIV Transgenic (TG26) mice (HIVAN animal model) were compared to wild type mice by immunostaining, immunoblotting and quantitative RT-PCR. TG26 mice had increased proteinuria and BUN. We found decreased AQP-4 levels in the renal medulla, increased endothelin-1, endothelin receptor A and reduced Sirtuin1 (SIRT-1) levels in TG26 mice. Also, oxidative and endoplasmic reticulum stress was enhanced in kidneys of TG26 mice. We provide the first evidence that AQP-4 is inhibited due to induction of HIV associated stress in the kidneys of TG26 mice which limits water reabsorption in the kidney which may be one of the cause associated with HIVAN, impairing kidney physiology. AQP-4 dysregulation in TG26 mice suggests that similar changes may occur in HIVAN patients. This work may identify new therapeutic targets to be evaluated in HIVAN.     

Binding of human von Willebrand factor to collagen and to collagen-stimulated platelets

Binding of von Willebrand factor (vWF) to collagen and to "collagen-stimulated platelets" was studied. Purified human iodine 125-labeled vWF binds to collagen. Binding was rapid, dependent on collagen and vWF concentration, independent of divalent ion concentration, and inhibited by unlabeled vWF as well as by high concentrations of fibronectin and fibrinogen. It was blocked by six monoclonal antibodies (MAbs) to human vWF (B200 through B205). Conversely, binding of 125I-vWF to platelets in the presence of collagen (collagen-treated platelets) was time dependent, saturable, and dependent on collagen, vWF, and divalent ion concentration. It was also inhibited by unlabeled vWF, fibronectin, or fibrinogen as well as by MAbs to vWF B200 through B205. In addition, binding of vWF to collagen-treated platelets was blocked by MAb to vWF 9 previously shown to inhibit binding of vWF to glycoprotein (GP) IIb-IIIa as well as by a MAb to GPIIb-IIIa. This binding was also strikingly decreased with use of patient platelets deficient in either GPIIb-IIIa or GPIa, whereas it was normal in the presence of a MAb to GPIb or when testing patient platelets deficient in GPIb. In conclusion, binding of vWF to platelets in the presence of collagen appeared to be a three-step phenomenon, including: binding of vWF to collagen; interaction of collagen with its receptor on the platelet membrane (GPIa ?), leading to activation of platelets and exposure of GPIIb-IIIa; and binding of vWF to GPIIb-IIIa.     

Long-term serologic follow-up of blood donors with biologic false reactivity on an anti-human T-cell lymphotropic virus Types I and II chemiluminescent immunoassay and implications for donor management

BACKGROUND: This study reports the results of the long‐term serologic follow‐up of blood donors who gave an index biologic false‐reactive (BFR) result on an anti‐human T‐lymphotropic virus Types I and II (HTLV‐I and ‐II) chemiluminescent immunoassay (ChLIA). STUDY DESIGN AND METHODS: All allogeneic whole‐blood and apheresis donors who gave an index BFR result on a HTLV‐I and ‐II ChLIA between May 10, 1997, and December 31, 2004, were included in the study. Donors were followed up for an additional 2 years until December 31, 2006. RESULTS: A total of 332 donors gave an index BFR donation during the study period. Donors were divided into five groups based on results of donations subsequent to the index BFR donation: 89 (26.8%) donors gave only nonreactive donations subsequent to the index BFR result, 56 (16.9%) donors gave only BFR donations, 43 (13.0%) gave one or more subsequent BFR donations before giving only nonreactive donations, 59 (17.8%) donors gave intermittent BFR and nonreactive donations, and 85 (25.6%) donors gave no further donations during the study period. The estimated mean duration of biologic false reactivity from the time of the index BFR donation in donors who gave only a single BFR result was 7.0 (1.4‐42.75) months and 23.3 (4.1‐92.25) months in those donors who gave several BFR results before giving nonreactive donations. Modeling of the data indicated that notification and deferral of donors after two consecutive BFR donations would result in the deferral of 143 of 332 (43.1%) of donors with an index BFR result while allowing donors to give three BFR results would reduce the number of deferred donors to 74 of 332 (22.3%). CONCLUSION: The results of this study indicate that although biologic false reactivity is usually transient, the time for resolution is variable. Allowing donors to give two or three BFR results before notification and deferral is one strategy that would substantially reduce the number of donors requiring deferral.     

Epizootiological importance of Glossina morsitans submorsitans (Diptera: Glossinidae) (Newstead) in the Ghibe River Valley, Southwest Ethiopia

The epizootiological importance of Glossina morsitans submorsitans in Ghibe River Valley was undertaken from October 2000 to September 2001. The flies were collected using baited monoconical traps. G. m. submorsitans occurred with a mean apparent density of 4.26 ± 0.49 flies/trap/day and the apparent density was characterized by an increase during the wet season and a decrease during the dry season. Among 450 G. m. submorsitans, approximately 5% were found to be infected with trypanosome. Of these infected flies, 76% were female. Nanomonas, Duttonella and Trypanozoon were the three trypanosome subgenera detected and occurred in the proportions of 57.1%, 38.1% and 4.8%, respectively. Among 139 blood meals of G. m. submorsitans collected, 54.68% were identified to group or species levels. Accordingly, 36.84%, 25%, 11.84% and 10.53% accounted for cattle, kudu, suidae (warthog and/or wild pig) and human, respectively and others such as goats (6.58%), bovidae (5.26%), baboon (2.63%) and water buck (1.32%). While 21.05% of the blood meals were found to be out of detection range.