Central opioid receptors differentially regulate the nalmefene-induced suppression of ethanol- and saccharin-reinforced behaviors in alcohol-preferring (P) rats.

The exact opioid-sensitive receptors participating in EtOH-seeking behaviors remains unclear. Previous studies have reported higher densities of micro-opioid receptor binding in the nucleus accumbens (NACC) of P relative to NP rats; however, no differences were seen in delta-receptor binding. In contrast to the NACC, substantially lower levels of micro-receptor binding have been observed in the ventral tegmental area (VTA) of both P and NP rats, albeit no line differences have been observed. In the present study, opioid receptors in the NACC, VTA, and hippocampus were evaluated for their capacity to regulate both EtOH- and saccharin-motivated behaviors in the genetically selected alcohol-preferring (P) rat. To accomplish this, nalmefene, an opiate antagonist with preferential binding affinity for the micro-opioid receptor was unilaterally or bilaterally infused during concurrent availability of 1 h daily EtOH (10% v/v) and saccharin (0.025 or 0.050% w/v) solutions. Rats performed under a two-lever fixed ratio (FR) schedule in which four responses on one lever produced the EtOH solution, and four on a second lever produced the saccharin solution. The results demonstrated that when responding maintained by both EtOH and saccharin are matched at basal levels, unilateral (1-60 microg) or bilateral (0.5-10 microg) microinjections of nalmefene into the NACC produced selective dose-dependent reductions on responding maintained by EtOH. Unilateral (40, 60 microg) and bilateral (10 microg) VTA infusions were also observed to selectively reduced EtOH responding; however, greater nalmefene doses were required and the magnitude of suppression on EtOH responding was markedly less compared with the NACC. The greater sensitivity of nalmefene to suppress EtOH responding in the NACC is likely due to the greater number of opioid receptors in the NACC relative to the VTA. Only bilateral infusion of the 40 microg dose in the NACC and VTA suppressed responding maintained by both EtOH and saccharin. In contrast, intrahippocampal infusions dose dependently suppressed EtOH- and saccharin-maintained responding over a range of doses (1-20 microg). The present study provides evidence that nalmefene suppresses EtOH-motivated behaviors via blockade of opioid receptors within the NACC and VTA, and under various dose conditions both reinforcer and neuroanatomical specificity can be observed.     

Comparison of different MRI sequences in lesion detection and early response evaluation of diffuse large B‐cell lymphoma – a whole‐body MRI and diffusion‐weighted imaging study

To compare different MRI sequences for the detection of lesions and the evaluation of response to chemotherapy in patients with diffuse large B‐cell lymphoma (DLBCL), 18 patients with histology‐confirmed DLBCL underwent 3‐T MRI scanning prior to and 1 week after chemotherapy. The MRI sequences included T₁‐weighted pre‐ and post‐contrast, T₂‐weighted with and without fat suppression, and a single‐shot echo‐planar diffusion‐weighted imaging (DWI) with two b values (0 and 800 s/mm²). Conventional MRI sequence comparisons were performed using the contrast ratio between tumor and normal vertebral body instead of signal intensity. The apparent diffusion coefficient (ADC) of the tumor was measured directly on the parametric ADC map. The tumor volume was used as a reference for the evaluation of chemotherapy response. The mean tumor volume was 374 mL at baseline, and decreased by 65% 1 week after chemotherapy (p < 0.01). The T₂‐weighted image with fat suppression showed a significantly higher contrast ratio compared with images from all other conventional MRI sequences, both before and after treatment (p < 0.01, respectively). The contrast ratio of the T₂‐weighted image with fat suppression decreased significantly (p < 0.01), and that of the T₁‐weighted pre‐contrast image increased significantly (p < 0.01), after treatment. However, there was no correlation between the change in contrast ratio and tumor volume. The mean ADC value was 0.68 × 10^–3 mm²/s at baseline; it increased by 89% after chemotherapy (p < 0.001), and the change in ADC value correlated with the change in tumor volume (r = 0.66, p < 0.01). The baseline ADC value also correlated inversely with the percentage change in ADC after treatment (r = ?0.62, p < 0.01). In conclusion, this study indicates that T₂‐weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI. Copyright © 2013 John Wiley & Sons, Ltd.     

Independent Origin of Plasmodium falciparum Antifolate Super-Resistance,Uganda, Tanzania,and Ethiopia

Super-resistant Plasmodium falciparum threatens the effectiveness of sulfadoxine–pyrimethamine in intermittent preventive treatment for malaria during pregnancy. It is characterized by the A581G Pfdhps mutation on a background of the double-mutant Pfdhps and the triple-mutant Pfdhfr. Using samples collected during 2004–2008, we investigated the evolutionary origin of the A581G mutation by characterizing microsatellite diversity flanking Pfdhps triple-mutant (437G+540E+581G) alleles from 3 locations in eastern Africa and comparing it with double-mutant (437G+540E) alleles from the same area. In Ethiopia, both alleles derived from 1 lineage that was distinct from those in Uganda and Tanzania. Uganda and Tanzania triple mutants derived from the previously characterized southeastern Africa double-mutant lineage. The A581G mutation has occurred multiple times on local Pfdhps double-mutant backgrounds; however, a novel microsatellite allele incorporated into the Tanzania lineage since 2004 illustrates the local expansion of emergent triple-mutant lineages.     

Investigation of Self-Healing Mortars with and without Bagasse Ash at Pre- and Post-Crack Times

Cracks in typical mortar constructions enhance water permeability and degrade ions into the structure, resulting in decreased mortar durability and strength. In this study, mortar samples are created that self-healed their cracks by precipitating calcium carbonate into them. Bacillus subtilus bacterium (10⁻⁷, 10⁻⁹ cells/mL), calcium lactate, fine aggregate, OPC-cement, water, and bagasse ash were used to make self-healing mortar samples. Calcium lactates were prepared from discarded eggshells and lactic acid to reduce the cost of self-healing mortars, and 5% control burnt bagasse ash was also employed as an OPC-cement alternative. In the presence of moisture, the bacterial spores in mortars become active and begin to feed the nutrient (calcium lactate). The calcium carbonate precipitates and plugs the fracture. Our experimental results demonstrated that cracks in self-healing mortars containing bagasse ash were largely healed after 3 days of curing, but this did not occur in conventional mortar samples. Cracks up to 0.6 mm in self-healing mortars were filled with calcite using 10⁻⁷ and 10⁻⁹ cell/mL bacteria concentrations. Images from an optical microscope, X-ray Diffraction (XRD), and a scanning electron microscope (SEM) were used to confirm the production of calcite in fractures. Furthermore, throughout the pre- and post-crack-development stages, self-healing mortars have higher compressive strength than conventional mortars. The precipitated calcium carbonates were primed to compact the samples by filling the void spaces in hardened mortar samples. When fissures developed in hardened mortars, bacteria became active in the presence of moisture, causing calcite to precipitate and fill the cracks. The compressive strength and flexural strength of self-healing mortar samples are higher than conventional mortars before cracks develop in the samples. After the healing process of the broken mortar parts (due to cracking), self-healing mortars containing 5% bagasse ash withstand a certain load and have greater flexural strength (100 kPa) than conventional mortars (zero kPa) at 28 days of cure. Self-healing mortars absorb less water than typical mortar samples. Mortar samples containing 10⁻⁷ bacteria cells/mL exhibit greater compressive strength, flexural strength, and self-healing ability. XRD and SEM were used to analyze mortar samples with healed fractures. XRD, FTIR, and SEM images were also used to validate the produced calcium lactate. Furthermore, the durability of mortars was evaluated using DTA-TGA analysis and water absorption tests.     

Ceramide changes in abdominal subcutaneous and visceral adipose tissue among diabetic and nondiabetic patients

BackgroundThis study profiles ceramides extracted from visceral and subcutaneous adipose tissue of human subjects by liquid chromatography‐mass spectrometry to determine a correlation with status of diabetes and gender.MethodsSamples of visceral and abdominal wall subcutaneous adipose tissue (n = 36 and n = 31, respectively) were taken during laparoscopic surgery from 36 patients (14 nondiabetic, 22 diabetic and prediabetic) undergoing bariatric surgery with a body mass index (BMI) >35 kg/m² with ≥1 existing comorbidity or BMI ≥40 kg/m². Sphingolipids were extracted and analyzed using liquid chromatography‐mass spectrometry.ResultsAfter logarithm 2 conversion, paired analysis of visceral to subcutaneous tissue showed differential accumulation of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) in visceral tissue of prediabetic/diabetic female subjects, but not in males. Within‐tissue analysis showed higher mean levels of ceramide species linked to insulin resistance, such as Cer(d18:1/18:0) and Cer(d18:1/16:0), in visceral tissue of prediabetic/diabetic patients compared with nondiabetic subjects and higher content of Cer(d18:1/14:0) in subcutaneous tissue of insulin‐resistant female patients compared with prediabetic/diabetic males. Statistically significant differences in mean levels of ceramide species between insulin‐resistant African American and insulin‐resistant Caucasian patients were not evident in visceral or subcutaneous tissue.ConclusionsAnalysis of ceramides is important for developing a better understanding of biological processes underlying type 2 diabetes, metabolic syndrome, and obesity. Knowledge of the accumulated ceramides/dihydroceramides may reflect on the prelipolytic state that leads the lipotoxic phase of insulin resistance and may shed light on the predisposition to insulin resistance by gender.     

Field efficacy of thermally expelled or live potted repellent plants against African malaria vectors in western Kenya

OBJECTIVE: To estimate the effectiveness of live potted plants and thermal expulsion of plant materials in repelling African malaria vectors in traditional houses in western Kenya. METHODS: Ocimum americanum, Lantana camara and Lippia ukambensis were tested in live, intact potted form whereas leaves of Corymbia citriodora, leaves and seeds of O. kilimandscharicum and O. suave were tested by thermal expulsion from modified traditional stoves. A latin square design was applied for randomly assigning the treatment and control plants to experimental houses over different nights. RESULTS: All plant species showed significant repellency against Anopheles gambiae sensu lato Giles (Diptera: Culicidae) (81.5%An. arabiensis Patton and 18.5%An. gambiae sensu stricto Giles), the main vectors of malaria in Africa, with the highest repellency by C. citriodora (48.71%, P < 0.0001) followed by an equal level of repellency of O. kilimandscharicum and O. suave (44.54%, P = 0.001) during application of plant material by thermal expulsion. All three plant species also showed a residual effect against An. gambiae s.l. with 36-44% repellency post-application period (22.30-06.30 hours) after a period of thermal expulsion. Similarly, intact potted plants of O. americanum and L. camara repelled An. gambiae s.l. significantly (37.91%, P = 0.004; and 27.22%, P = 0.05, respectively). Thermal expulsion of leaves and seeds of O. kilimandscharicum significantly repelled An. funestus Giles, although none of the potted plants repelled this species. CONCLUSION: Both methods of application may offer cost-effective alternatives as additional means of household protection, and a useful complement to bed nets, particularly for the early part of the evening before bedtime.     

Traditional use of mosquito-repellent plants in western Kenya and their evaluation in semi-field experimental huts against Anopheles gambiae: ethnobotanical studies and application by thermal expulsion and direct burning

Ethnobotanical survey in 2 communities in western Kenya revealed that the most commonly known repellent plants were Ocimum americanum L. (64.1%), Lantana camara L. (17.9%), Tagetes minuta L. (11.3%) and Azadirachta indica A. Juss (8.7%) on Rusinga Island, and Hyptis suaveolens Poit. (49.2%), L. camara (30.9%) and O. basilicum L. (30.4%) in Rambira. Direct burning of plants is the most common method of application for O. americanum (68.8%), L. camara (100%) and O. basilicum (58.8%). Placing branches or whole plants inside houses is most common for H. suaveolens (33.3 and 57.8% for the respective locations), A. indica (66.7 and 100%), and T. minuta (54.8 and 56.0%). The repellency of plants suggested by the ethnobotanical survey and other empirical information was evaluated against the malaria vector Anopheles gambiae s.s. Giles in experimental huts within a screenwalled greenhouse. Thermal expulsion and direct burning were tested as alternative application methods for the selected plants O. americanum, O. kilimandscharicum Guerke, O. suave Willd., L. camara, A. indica, H. suaveolens, Lippia uckambensis Spreng and Corymbia citriodora Hook. When thermally expelled, only H. suaveolens failed to repel mosquitoes, whereas the leaves of C. citriodora (74.5%, P < 0.0001), leaves and seeds of O. suave (53.1%, P < 0.0001) and O. kilimandscharicum (52.0%, P < 0.0001) were the most effective. Leaves of C. citriodora also exhibited the highest repellency (51.3%, P < 0.0001) by direct burning, followed by leaves of L. uckambensis (33.4%, P = 0.0004) and leaves and seeds of O. suave (28.0%, P = 0.0255). The combination of O. kilimandscharicum with L. uckambensis repelled 54.8% of mosquitoes (P < 0.0001) by thermal expulsion. No combination of plants increased repellency by either method. The semi-field system described appears a promising alternative to full-field trials for screening large numbers of candidate repellents without risk of malaria exposure.     

Graves' thyroid ophthalmopathy in Ethiopian patients

In a prospective study, we evaluated the clinical manifestations, severity, complication and management of Graves' thyroid ophthalmopathy (GTO) in 37 Ethiopian patients. Twenty-seven were females and 10 were males (F:M = 2.7:1). The mean age was 35 years (range 19-70 yrs). The mean duration of ocular symptoms was 33.4 months (range 2-120 months) while the mean duration of hyperthyroid symptoms was 36.2 months (range 6-120 months). GTO was found in 30 (81.1%) hyperthyroid, 1 (2.7%) hypothyroid and 5 (13.5%) euthyroid patients. Upper lid retraction was the most common clinical finding, being detected in 31 (83.8%) of the patients. One (2.7%) patient had marked extraocular muscle involvement, involving the inferior rectus muscle of one eye. Though 18 (48.6) patients had signs of soft tissue inflammation, only 4 (10.8%) required the administration of systemic steroids to control the inflammatory process. None of our patients had sight loss from the complications of GTO. Larger prospective studies are suggested to evaluate both the prevalence and possible racial difference in its clinical presentation.     

Establishing a simple and sustainable quality assurance program and clinical chemistry services in Eritrea

BACKGROUND: As chronic diseases become more prevalent in developing nations, establishment of sustainable clinical chemistry services will become increasingly important. The complexity of automated instruments, coupled with a lack of resources and skilled workers, will present a challenge for these countries. METHODS: A system emphasizing simplified instrumentation, single source reagents, technical education and support, and simple QC algorithms was established in the small African nation of Eritrea. The same reagents were used on different analyzers, as well as the same lot numbers of QC material. To allow traceability of Eritrea results to an accredited US laboratory, the reagents and QC materials were identical to those used in a large university hospital in the US, and patient samples were frequently exchanged between locations. RESULTS: QC values for 23 clinical chemistry tests in the Eritrean National Health Laboratory compared well to values obtained in the US, showing some statistically different values but no clinically significant differences. QC values were also stable over time in Eritrea. Patient sample values from Eritrea correlated well to values from the US, with r values ranging from 0.71 to 0.99. For 9 chemistry tests, small regional laboratories in Eritrea produced QC and patient values that usually compared well to those from the Eritrea National Health Laboratory, but markedly discrepant values were occasionally observed that prompted investigation. CONCLUSION: A simple but sustainable national laboratory system has been established in the developing nation of Eritrea.     

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.