Filariasis in Africa—treatment challenges and prospects

Lymphatic filariasis (LF) and onchocerciasis are parasitic nematode infections that are responsible for a major disease burden in the African continent. Disease symptoms are induced by the immune reactions of the host, with lymphoedema and hydrocoele in LF, and dermatitis and ocular inflammation in onchocerciasis. Wuchereria bancrofti and Onchocerca volvulus, the species causing LF and onchocerciasis in Africa, live in mutual symbiosis with Wolbachia endobacteria, which cause a major part of the inflammation leading to symptoms and are antibiotic targets for treatment. The standard microfilaricidal drugs ivermectin and albendazole are used in mass drug administration programmes, with the aim of interrupting transmission, with a consequent reduction in the burden of infection and, in some situations, leading to regional elimination of LF and onchocerciasis. Co-endemicity of Loa loa with W. bancrofti or O. volvulus is an impediment to mass drug administration with ivermectin and albendazole, owing to the risk of encephalopathy being encountered upon administration of ivermectin. Research into new treatment options is exploring several improved delivery strategies for the classic drugs or new antibiotic treatment regimens for anti-wolbachial chemotherapy.     

HTLV-I infection in the South West Indian Ocean islands, particularly in La Réunion and the Seychelles

Data on HTLV-I are scarce in several Southwest Indian Ocean islands except for La Réunion and The Seychelles. The two cases of HTLV-I have been confirmed by Western-Blot in La Réunion, among blood donors. In Seychelles (87 400 inhabitants in 2012), where blood donors and some other cases are screened, HTLV-I was confirmed with a line immune assay in 43 persons and at least 10–20 patients are known to have tropical spastic paraparesia or adult T-cell lymphoma associated with HTLV-I. In the south-west Indian Ocean, a possibly important other issue may be co-infection of HTLV-1 with the Strongyloides stercoralis roundworm, which is endemic in all countries of the region and which can sometimes lead to severe symptomatic infestation.     

Malaria vectors, epidemiology, and the re-emergence of Anopheles darlingi in Belém, Pará, Brazil

An evaluation of malaria transmission and epidemiology in the Amazonian city of Belém over the last 70 years shows that (1) Anopheles darlingi, reported to be eradicated in 1968, reappeared in the mid 1990s, with a marked increase in abundance between 1997 to 1999 in two of three districts sampled; (2) An. darlingi and An. aquasalis are each implicated in current malaria transmission in different districts of the city; (3) mosquito species diversity (in Anopheles subgenus Nyssorhynchus) has increased from two in the 1930s to six in the 1940s to 10 in the 1990s; (4) there is no overall correlation between malaria case incidence and human population size from 1940 to 1996 in Belém; (5) however, the total number of malaria cases has increased significantly since the late 1970s and over the short term from 1993 to 1999; and (6) interestingly, the short term increases are due solely to cases of Plasmodium vivax infection; cases of P. falciparum malaria are declining (significantly for Pará state only). The reappearance of An. darlingi may be a result of the continued expansion of Belém into the surrounding forest in the 1990s. In the absence of preventative measures, we predict an increase in local outbreaks of malaria in the DAENT and DAICO districts where the population sizes of An. darlingi are increasing.     

Immunohistochemical investigation of the angiogenic proteins VEGF,HIF-1α and CD34 in invasive ductal carcinoma of the breast

The expression of prognostic markers in cancer has become important in diagnostic routine and research. A high mitotic rate compromises the individual cell access to oxygen and nutrients, due to reduced blood supply. Cells undertake adaptive measures such as vascular endothelial growth factor (VEGF), expressed under the control of hypoxia-inducible factor-1α (HIF-1α). CD34 is an endothelial marker which can show the presence and distribution of blood vessels. This study evaluated the presence and relative expression of VEGF, HIF-1α and CD34 using immunohistochemistry of 60 breast tumors and double staining, correlating the findings with clinical and pathological variables. High VEGF expression was correlated with low cell proliferation, lymph node-negative, smaller tumor size and patients not receiving hormone therapy. High HIF-1α expression predominated in younger (<50-year) patients, subjected to neo-adjuvant therapy and in p53-negative tumors. Absence of metastasis, radiotherapy or hormone treatment, and estrogen receptor (ER)-positive tumors showed high CD34 immunoreactivity. We suggest that the angiogenic factors VEGF, HIF-1α and CD34 are important in breast cancer progression and their abundance in breast tumors has prognostic and predictive value.     

Does age play a role in the structure of anxiety and depression in children and youths? An investigation of the tripartite model in three age cohorts

Although previous studies provide some support for a tripartite model of relations between anxiety and depression in children there is evidence to suggest that anxiety and depression may be increasingly differentiated over development. Using a confirmatory factor analytic strategy with rationally selected item sets from the Revised Children's Manifest Anxiety Scale and the Children's Depression Inventory, the current study sought to test unitary, dual, and tripartite models for anxiety and depression in a cross-sectional design using 3 narrow-band age cohorts of nonreferred children and youths. The results found little evidence of increasing differentiation. All models provided a moderate fit to the data, with some evidence that a correlated 3-factor model was the preferred model in all age cohorts. Further research is required to explore the discriminant validity and clinical utility of the tripartite dimensions in childhood populations.     

Cardiac dimensions, physical activity, and submaximal working capacity in youth of the Québec Family Study

The relationships between cardiac dimensions and physical activity and submaximal working capacity were examined in 198 boys and 154 girls, aged 9–18 years, who were participants in the first phase of the Québec Family Study. The sample was divided into three age groups, 9–12 years, 13–15 years, and 16–18 years. Indicators of physical activity included estimated daily energy expenditure (EE) and time spent in moderate-to-vigorous physical activity (median metabolic equivalents of energy expenditure above resting metabolic rate ≥4.8). Submaximal physical working capacity (PWC₁₅₀) was determined using a submaximal exercise test on a Monark cycle ergometer. Echocardiographically determined dimensions included posterior wall thickness, septal wall thickness, and left ventricular mass (LVM). The analyses were based on partial correlation and analysis of covariance, controlling for age and body surface area. Relationships between EE/physical activity variables and cardiac dimensions were low and, at best, moderate (r < 0.45). With subjects grouped into tertiles by indicators of physical activity, LVM was significantly different only among 16- to 18-year-old girls (157 g vs 134 g in the highest and lowest quartiles, respectively; P < 0.05). Correlations between cardiac dimensions and PWC₁₅₀ were also low (r < 0.30), with few significant relationships. In general, cardiac dimensions were not related to habitual physical activity and PWC₁₅₀ in young subjects aged 9–18 years. However, significant correlations were positive, as expected. LVM may be related to submaximal power output in boys since it accounts for 3% of the variance, after adjusting for age and BSA. Received: 4 January 1999 / Accepted: 8 June 1999     

Skeletal muscle,autophagy, and physical activity: the ménage à trois of metabolic regulation in health and disease

Metabolic homeostasis is essential for cellular survival and proper tissue function. Multi-systemic metabolic regulation is therefore vital for good health. A number of tissues have the task of maintaining appropriate metabolism, and skeletal muscle is the most abundant of them. Muscle possesses a remarkable plasticity and is able to rapidly adapt to changes in energetic demands by fine-tuning the balance between catabolic and anabolic processes. Autophagy is a catabolic process responsible for the degradation of protein aggregates and damaged organelles, through the autophagosome–lysosome system. Proper regulation of autophagy flux is fundamental for organism homeostasis under physiological conditions and even more in response to metabolic stress, such as during physical activity and nutritional deficits. Both deficient and excessive autophagy are harmful for health and have devastating consequences in a myriad of pathologies. The regulation of autophagy flux in various tissues, and in particular in skeletal muscle, is of great importance for health and tissue homeostasis and represents a feasible mechanism by which physical exercise exerts its beneficial effects on muscle and whole body metabolism. This review is focused on the key molecular mechanisms regulating macromolecule and organelle turnover in muscle during alterations in nutrient availability and energetic demands, as well as their involvement in disease pathogenesis.     

BamH1 polymorphism in the Chinese,Malays, and Indians in Singapore and its application in the prenatal diagnosis of β-thalassemia

Summary The distribution of restriction fragment length polymorphism (RFLP) at theBamH1 site of the -globin gene was investigated in the Chinese, Indian, and Malay race in Singapore. The sample comprised of 183 normal individuals and 35 -thalassemia carriers in which 13 were couples with at least one -major child. The results from this study indicate thatBamH1 polymorphism will be informative in 22% of pregnancies at risk for -thalassemia major in Chinese, 19% in Malays and 7% in Indians. In prenatal diagnosis usingBamH1 polymorphism for one -major affected family, the fetus was diagnosed to be normal or -carrier. The validity ofBamH1 polymorphism in the exclusion of -thalassemia major was subsequently confirmed at birth by globin chain biosynthesis.     

Syndromes mononucléosiques et pathologies hématologiques liés au virus d'Epstein-Barr

The Epstein-Barr virus (EBV), which preferentially infects B cells, persists in the infected subject as a latent asymptomatic infection. In adolescents, infectious mononucleosis is the symptomatic manifestation of primary EBV infection. The viral latency in the memory B-cells, the reservoir cells in peripheral blood in individuals is controlled by CD4 and CD8 positive T-cells. Immunodeficient patients are at high risk of developing EBV driven B-cell lymphomas as the consequence of the expression of oncogenic latency proteins LMP1 and EBNA2. These proteins expressed in infected B cells identify latency III or proliferation program in virus transformed B-cell, leading to lymphoid proliferation. In addition to immunodeficiency-related lymphomas, the most frequent lymphoid malignancies associated with EBV are the endemic Burkitt lymphoma, Hodgkin lymphoma and nasal type T-cell lymphoma.     

Direct-acting mutagenic activity in white, rosé, and red wines with the Ara test of Salmonella typhimurium.

Thirty-two commercially produced white, rosé, and red wines from Spain were assayed for genotoxicity. The Ara forward mutagenicity assay with Salmonella typhimurium served as the test system. All the wines were mutagenic in the absence of mammalian microsomal activation (S9 mix) and/or glycosidase activities with the exception of one rosé wine which gave a clear dose-response relationship, although its mutagenic potency was considered statistically nonsignificant. The mutagenic activity covered nearly a 30-fold range. Compared to white and rosé wines, red wines showed the highest levels of mutagenicity; this wine type included four "very potent" (greater than 3,000 AraR mutants/ml) mutagenic wines. The level of wine mutagenicity did not correlate with either the region or the year of production (vintage). Individual winery methods are suggested as primarily responsible for variations in mutagenic activity. The present study with the Ara test supports the possibility that wine components other than the flavonols quercetin and rutin are the major putative mutagens: (1) white wines, as well as rosé or red wines, were detected as being mutagenic; (2) in no case was activation required for the detection of mutagenicity; (3) mutagen(s) were detected mainly (red wine) when not exclusively (white and rosé wine) in the polar fraction from XAD-2 chromatography. The high sensitivity of the Ara test has allowed the screening of the mutagenicity of a variety of wines with no previous process of extraction or concentration. The comparison of the mutagenic activity of the entire complex mixture to that of its lyophilized residue has revealed a positive synergistic role for ethanol in the mutagenicity of certain wines. Finally, this work suggests that the Ara test is a useful tool for mutagenicity screening in wines. Thus, this test might play an important role in elucidating the genotoxic mechanism of action of alcoholic beverages, and for studying optional production methods to decrease the mutagenicity of commercial wines.     

Can the laboratory affect the investigation and diagnosis of primary biliary cirrhosis?

BACKGROUND: Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterised by the presence of various laboratory abnormalities but the precise role of laboratory staff in initiating clinical referral and subsequent biopsy is not clear. OBJECTIVE: To examine the impact of laboratory abnormalities in the investigation of PBC. METHODS: In a retrospective study of laboratory results over nine years from 1996, computer records were reviewed to identify how many referrals for biopsy were initiated and subsequent diagnoses made as a result of clinical signs, raised serum alkaline phosphatase activity (ALP), raised IgM concentration, or positive mitochondrial antibodies accompanied by a clinical comment from the laboratory suggesting further action. RESULTS: 22 diagnoses of PBC were confirmed by histopathology. Eleven had high ALP activity which had follow up tests initiated by the laboratory (mitochondrial antibodies or IgM or both) and a comment added suggesting further investigation into the possibility of PBC. Seven had abnormal liver antibodies and one had a high polyclonal IgM concentration which prompted the relevant follow on testing and comments. One had an earlier diagnosis made on serological/clinical grounds and the biopsy was a confirmatory measure. One had no liver related antibodies. One had a request by laboratory staff for follow on tests but these were not asked for in subsequent samples by the requesting clinician. CONCLUSIONS: There is a positive role for laboratory staff in the diagnosis of PBC. Unexplained rises in ALP activity, positive mitochondrial antibodies, or raised IgM concentrations should be investigated more fully by laboratory staff and advice given to prompt a clinical referral for review and biopsy.     

Identification and characterization of the ribosome-associated protein, HrpA, of Bacillus Calmette-Guérin

HrpA was found as a ribosome-associated protein which appeared in heat-stressed Mycobacterium bovis Bacillus Calmette-Guérin. Here, we have studied the function of HrpA in vitro. HrpA is a heat shock protein belonging to a small heat shock protein family. The putative molecular mass was 17784.86 kDa. Recombinant HrpA formed large complexes of nonamer or dodecamer. HrpA prevented the aggregation of enzymes under heat shock conditions, and it formed stable complexes with partially denatured enzymes. HrpA was induced temporarily by oxygen repletion after anaerobic condition.