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41.
Powell R  Barengolts D  Mayr L  Nyambi P 《Viruses》2010,2(2):639-654
West-Central Africa is an epicenter of the HIV pandemic; endemic to Cameroon are HIV-1 viruses belonging to all (sub)subtypes and numerous Circulating Recombinant Forms (CRFs). The rural villages of Cameroon harbor many strains of HIV-1, though these areas are not as well monitored as the urban centers. In the present study, 82 specimens obtained in 2000 and 2001 from subjects living in the rural villages of the South and West Regions of Cameroon were subtyped in gag, pol, and env and compared to 90 specimens obtained in 2006-2008 in the same regions, in order to analyze HIV-1 evolution in these rural areas. It was found that in the South Region, the proportion of unique recombinant forms (URFs) remained constant (~40%), while the amount of URFs containing fragments of a CRF increased by 25%. (Sub)subtypes A1, F2, H, and K, and CRF09_cpx, identified in 2000 and 2001, were replaced by CRFs 01_AE, 13_cpx, 14_BG, and 18_cpx in 2006-2008. In the West Region, (sub)subtypes A2, C, G, and H, and CRFs 01_AE and 09_cpx, identified in 2000-2001, were replaced by sub-subtype A1 and CRFs 25_cpx and 37_cpx in 2006-2008. The proportion of URFs in the West Region dropped significantly over the time period by 43%. In both Regions, the proportion of CRF02_AG increased at all loci. These findings demonstrate that the evolution of HIV-1 is distinct for each endemic region, and suggests that the proportion of URFs containing CRF fragments is increasing as the genetic identity of the virus continues to shift dramatically. This highlights the concern that subtype-specific vaccines may not be relevant in Cameroon, and that the distribution of viral diversity in these regions of Cameroon must be carefully monitored.  相似文献   
42.
We evaluated the influence of allelic frequency of the human leukocyte antigen (HLA) -DRB1 on the acquisition of antibody response against malaria sporozoite and merozoite peptides in patients with Plasmodium vivax malaria acquired in endemic areas of Brazil. IgG antibodies were detected by enzyme-linked immunosorbent assay against four peptides of circumsporozoite protein (CSP) (amino, carboxyl, and VK210 and VK247 repeats) and peptides of merozoite surface protein 1 (MSP-1), apical membrane antigen 1 (AMA-1), and Duffy-binding protein (DBP). We found an association between HLA-DR3 and HLA-DR5 alleles and lack of antibody response to CSP amino terminal, as well as an association between HLA-DR3 and the highest antibody response to MSP1 (Pv200L). In conclusion, we suggest a potential regulatory role of the HLA-DRB1 alleles in the production of antibodies to a conserved region of P. vivax CSP and MSP1 in Brazilian population exposed to malaria.  相似文献   
43.
44.
Lipoma arborescens is a benign tumor, but it may be a reactive process to other disorders, and its clinical, analytical, radiological and ultrasound presentation may be redundant to any synovial tumor. Despite the characteristic feature on magnetic resonance imaging (MRI), the correct differential diagnosis in atypical presentation, and the need for timely removal of the lesion to prevent joint damage, forces, ultimately, to invasive procedures. The clinical case reported here, fourth described in English language publications on the polyarticular form, also presented other specificities related to one of the swellings, in the knee. Because of its atypical location in the popliteal fossa, recurrent episodes of joint effusion, personal history of knee trauma, pulmonary tuberculosis, and family history of rheumatoid arthritis required particular attention. This process was hampered by the refusal of knee (and ankle) surgery by the patient. He accepted surgical removal of the swellings of the wrists, for aesthetical reasons, with pathologic confirmation of the diagnosis, and clinical success in that location. MRI of the knee showed the typical image of lipoma arborescens, but also other changes that compromise the prognosis.  相似文献   
45.
46.
Understanding the pathogenesis of Plasmodium vivax malaria is challenging. We hypothesized that susceptibility to P. vivax-induced thrombocytopenia could be associated with polymorphisms on relevant platelet membrane integrins: integrin α2 (C807T), and integrin β3 (T1565C). Although β3 polymorphism was not related with P. vivax malaria, α2 807T carriers, which show high levels of integrin α2β1, had a higher probability for severe thrombocytopenia than wild-type carriers. This evidence of the association of integrin polymorphism and P. vivax morbidity was further demonstrated by a moderate but significant correlation between clinical disease and surface levels of the integrin α2β1.Plasmodium vivax infection is no longer considered a benign disease because it might cause severe or fatal episodes.1,2 Although the mechanisms underlying P. vivax-induced pathogenesis remain poorly studied, thrombocytopenia is frequently observed in P. vivax infection.3 Recent studies suggest an association between deep thrombocytopenia and severity of the illness.4 However, the mechanisms leading to thrombocytopenia, as well as its contribution to malaria pathogenesis, are not well understood.Besides their central role in homeostasis, platelets contain a wide range of inflammatory, immune-modulating, and angiogenic factors. Consequently, it is not surprising that the role of platelets in the development of an array of disorders continues to emerge.5 Although P. vivax-induced thrombocytopenia has not been investigated in detail,3 several lines of evidence suggest that platelets participate actively in the pathogenesis of malaria.6 In P. vivax malaria, platelets release microparticles into the circulation, and these platelet-derived microparticles seem to be associated with acute inflammatory symptoms of disease.7 In addition, we have shown that levels of plasma cell-free circulating nucleic acids were closely correlated with platelet counts, increasing in a linear fashion with the spectrum of P. vivax malaria.8 On the basis of these observations, we hypothesized that platelet receptor polymorphisms that result in a gain of function in platelet adhesion and/or aggregation in vivo might place carriers at increased risk for P. vivax-induced thrombocytopenia.We studied the association between P. vivax and polymorphisms of platelet integrins (cell-surface heterodimeric proteins that mediate cell-matrix and cell-cell interactions9). The focus of this study was two gain-of-function platelet receptor single-nucleotide polymorphisms: the C807T polymorphism of integrin α2 (also known as platelet glycoprotein Ia, GPIa) and the T1565C of integrin β3 (platelet glycoprotein IIIa, GPIIIa). Both polymorphisms have been implicated in different clinical events, including those related to the coronary syndromes, probable because of their gain-of-function mechanisms.10,11 Integrin α2, a platelet receptor for collagen, forms a functional receptor with the integrin β1 subunit, which is essential for platelet function.9 The C807T single nucleotide polymorphism (single-nucleotide polymorphism no. rs1126643; National Center for Biotechnology Information, Bethesda, MD) is considered a genetic marker of the integrin α2β1 density.12,13 Integrin β3, a common β subunit for β3-integrins, such as αIIbβ3, has a key role in platelet function by binding fibrinogen and von Willebrand factor (vWF),14 and the T1565C polymorphism (rs5918) seems to increase platelet aggregation.15 To the best of our knowledge, there has been no study that assessed the association between integrin polymorphisms and P. vivax malaria.A total of 150 P. vivax patients 2–78 years of age were enrolled in the study after written informed consent, as specified by the Brazilian National Council of Health (Protocol CEPSH/CPqRR/03/2008). Antimalarial and supportive therapies were given according to standard protocols. The study included patients with symptomatic but uncomplicated P. vivax malaria, and all volunteers were negative for P. falciparum and/or P. malariae by microscopy and polymerase chain reaction. Demographic, clinico-epidemiologic, and hematologic data of P. vivax-infected volunteers are shown in
CharacteristicValue
Sex, M:F3:1
Age, median (range)36 (2–78)
Malaria episodes, median (range)*2 (0–60)
Parasites/μL, median (range)1,219 (25–8,238)
Hematocrit %, median (range)39 (14–51)
Hemoglobin, g/dL, median (range)13 (5–17)
Leukocyte count/mm3 (×103), median (range)5.5 (2.0–14.6)
Platelet count/mm3 (×103), median (range)98 (13–260)
Thrombocytopenia, no. (%)124 (83)
Severe thrombocytopenia, no. (%)25 (17)
Length of symptoms, days, median (range)4 (1–50)
Fever at the time of blood sampling, no. (%)113 (77)
Open in a separate window*Self-reported number of lifetime malaria episodes.Platelet count ≤ 150,000/mm3.Platelet count ≤ 50,000/mm3; this criterion has been used in several malaria studies, including those carried-out in the Amazon area.3Because there are no clear criteria to define P. vivax-induced morbidity, we used a previously validated semi-quantitative clinical assessment to enable numerical comparisons.8 In brief, scores of 0 or 1 were assigned to clinical and hematologic parameters reported as absent (or within reference ranges) or present (or outside reference ranges), respectively; the sum of scores provides the patient''s final clinical score (scores range from 0 to 5). Determination of α2 C807T and β3 T1565C integrin genotypes was performed by using polymerase chain reaction–restriction fragment length polymorphism assays with restriction enzymes TaqI (integrin α2) and MspI (integrin β3), as described.16The prevalence of integrin α2 C807T genotypes in P. vivax patients were 35% CC, 55% CT and 10% TT, and overall allele frequencies were C = 63% and T = 37%. The frequency of P. vivax patients who showed the highest receptor density (807T allele) was similar to that reported for healthy persons in a meta-analysis of seven independent studies (approximately 1,000 healthy persons); 37% were 807T allele carriers.17To determine the impact of α2 C807T polymorphic variation on susceptibility to morbidity, we stratified patients according to clinical and hematologic data. Results showed that median platelet counts for P. vivax patients carrying the 807T allele (90,500/mm3, interquartile range = 53,000–128,500/mm3) was significantly lower than for patients carrying the wild-type allele (101,000/mm3, interquartile range = 70,000–139,250/mm3) (P = 0.0228, by non-parametric Wilcoxon Mann-Whitney test). There was a weak trend toward decreased platelet counts according to the number of mutated alleles (median platelet count = 85,000/mm3 for two mutated alleles and 91,500 for one mutated allele). The general trend of low platelet counts among patients carrying one or two mutated alleles (χ2 for trend = 5.18, P = 0.022) is shown in Figure 1A. The 807T allele was predominantly associated with severe thrombocytopenia (platelets counts < 50,000/mm3) but not with moderate thrombocytopenia (platelet counts = 50,000–100,000/mm3).Open in a separate windowFigure 1.Influence of integrin α2 C807T polymorphism, but not integrin β3 T1565C polymorphism, on Plasmodium vivax–induced thrombocytopenia. Genotype distributions of A, integrin α2 C807T and B, integrin β3 T1565C according to platelet levels among 150 P. vivax malaria patients. Results are frequency of persons carrying two (homozygous), one (heterozygous), or no mutated allele.Using the wild-type genotype CC as a reference, we found that the TT genotype was associated with an increased probability for severe thrombocytopenia (adjusted odds ratio [OR] = 10.31, 95% confidence interval [CI] = 2.13–49.79, P = 0.004) (Figure 2). Also, P. vivax patients with the variant genotypes (CT and TT) had a significantly higher risk for severe thrombocytopenia than patients with the CC genotype (adjusted OR = 4.44, 95% CI = 1.23–15.99, P = 0.023).Open in a separate windowFigure 2.Odds ratio (ORs) analysis for the association of integrin α2 C807T polymorphism among P. vivax malaria patients with severe thrombocytopenia (platelet counts ≤ 50,000/mm3). Crude OR was obtained by using 2 × 2 contingency tables with a 95% confidence interval (CI), and the adjusted OR was calculated by using the unconditional logistic regression method with adjustment for age, sex, and previous malaria. P < 0.05 was considered significant (bold).To make numerical comparisons between integrin α2β1 levels and clinical spectrum of P. vivax malaria, we scored persons according to integrin α2β1 levels as follows: score = 2 (homozygous for the 807T allele), score = 1 (heterozygous for the 807T allele), and score = 0 (no 807T allele). This criterion was used because 807 C/T dimorphism is a genetic marker of integrin α2β1 levels, and platelets carrying the TT genotype express the highest levels, TC platelets express intermediate levels, and CC platelets express the lowest levels.13,18Using this semi-quantitative assessment, we demonstrated a moderate but significant correlation between intensity of clinical malaria and surface levels of the integrin α2β1 (Spearman r = 0.2, P = 0.011). Nevertheless, the present study precludes any definite conclusion about clinical disease and integrin α2β1 because it deals only with uncomplicated P. vivax malaria. To properly address this question, a follow-up study would be desirable, which included patients with different degrees of malaria.The β3 integrin genotype distribution among P. vivax patients showed that the frequencies of the heterozygous (TC) and homozygous (CC) mutations of T1565C were 18.7% and 0.8%, respectively, with a predominance of the TT genotype (n = 99, 80.5%). The allele frequencies (90% T and 10% C) we report confirm those of previous studies, which showed that usually more than 80% of the human population harbors the T1565 allele.19 In P. vivax patients stratified according to platelet counts, we did not find evidence supporting an association between P. vivax thrombocytopenia and the T1565C polymorphism of integrin β3 (Figure 1B); the T versus C allele comparison showed an adjusted OR of 1.55 (95% CI = 0.44–5.47, P = 0.419). No evidence of any gene-disease association was obtained comparing the T1565C polymorphism of the integrin β3 among P. vivax patients. However, because of the low frequency of CC homozygotes in our sample and the high frequency of polymorphisms in integrin β3,20 it is not appropriate to exclude a role for β3 integrin in P. vivax-induced thrombocytopenia. In this context, it would be of interest to investigate polymorphisms in the major vWF receptor, glycoprotein-1b (GP1b), because studies have implicated endothelial cell activation with release of active vWF as one pathogenic mechanism contributing to malaria-induced thrombocytopenia.21The pathogenic mechanism involved in the association between hereditary variation in platelet integrin α2β1 density and P. vivax-induced thrombocytopenia is unknown. Nevertheless, our evidence showed that the integrin α2 C807T polymorphism is associated with an increased risk for P. vivax-induced severe thrombocytopenia is according to the fact that the coagulation-inflammation cycle acts as a cofactor for malaria morbidity.22 In this context, if one considers recent findings that suggest that P. vivax malaria is associated with excessive endothelial activation and inflammation,23,24 one could speculate that perturbed endothelia induced by malaria infection would potentiate an exacerbate platelet-collagen interaction in α2 807T carriers, whose propensity for collagen-induced platelet aggregation/activation is increased.Previous finding suggest that thrombocytopenia in persons with malaria might be related to endothelial damage.25 Furthermore, because platelet activation by agonists such as collagen or thrombin also leads to vesiculation of the platelet membrane and formation of microparticles, this mechanism might amplify P. vivax-induced inflammation and contribute to reduced platelet lifespan in malaria patients. We have demonstrated that platelet-derived microparticles might play a role in acute inflammatory symptoms of P. vivax malaria.7 However, a relationship between α2 polymorphism and P. vivax thrombocytopenia remains unclear because the contribution of endothelial activation in the pathophysiology of P. vivax malaria, as well as mechanisms involved in thrombocytopenia, are unknown.3 Thus, a useful field of investigation would be the role of platelets and surface integrin receptors in P. vivax cytoadhesion, which is a not well-defined phenomenon traditionally associated with P. falciparum infection.26Because ancestry might play a role in the prevalence of integrin genotypes,27 it is important to explore whether regional differences in the hematologic status of P. vivax malaria28 are linked to differences in ancestral origins of the study population. Unfortunately, there is little information on integrin polymorphisms in malaria-endemic areas. Consequently, a more comprehensive search for polymorphisms/haplotypes of different integrins may provide additional insight into the role of integrin genetics in malaria.In conclusion, the present study provides evidence that an integrin α2 C807T polymorphism is associated with an increased risk of P. vivax-induced severe thrombocytopenia. It remains to be clarified whether this polymorphism is linked to other relevant mutations. Because the number of cases was relatively small and hematologic variables were obtained at the time of diagnosis, our findings should be interpreted with caution before being confirmed in larger studies. This preliminary study provides a valuable guidance for the future studies in this area.  相似文献   
47.
IL-10-producing Th1 cells possess a distinct molecular signature in malaria     
Chelsea L. Edwards  Susanna S. Ng  Fabian de Labastida Rivera  Dillon Corvino  Jessica A. Engel  Marcela Montes de Oca  Luzia Bukali  Teija C.M. Frame  Patrick T. Bunn  Shashi Bhushan Chauhan  Siddharth Sankar Singh  Yulin Wang  Jinrui Na  Fiona H. Amante  Jessica R. Loughland  Megan S.F. Soon  Nicola Waddell  Pamela Mukhopadhay  Lambros T. Koufariotis  Rebecca L. Johnston  Jason S. Lee  Rachel Kuns  Ping Zhang  Michelle J. Boyle  Geoffrey R. Hill  James S. McCarthy  Rajiv Kumar  Christian R. Engwerda 《The Journal of clinical investigation》2023,133(1)
  相似文献   
48.
Rabies in southeast Brazil: a change in the epidemiological pattern     
Queiroz LH  Favoretto SR  Cunha EM  Campos AC  Lopes MC  de Carvalho C  Iamamoto K  Araújo DB  Venditti LL  Ribeiro ES  Pedro WA  Durigon EL 《Archives of virology》2012,157(1):93-105
This epidemiological study was conducted using antigenic and genetic characterisation of rabies virus isolates obtained from different animal species in the southeast of Brazil from 1993 to 2007. An alteration in the epidemiological profile was observed. One hundred two samples were tested using a panel of eight monoclonal antibodies, and 94 were genetically characterised by sequencing the nucleoprotein gene. From 1993 to 1997, antigenic variant 2 (AgV-2), related to a rabies virus maintained in dog populations, was responsible for rabies cases in dogs, cats, cattle and horses. Antigenic variant 3 (AgV-3), associated with Desmodus rotundus, was detected in a few cattle samples from rural areas. From 1998 to 2007, rabies virus was detected in bats and urban pets, and four distinct variants were identified. A nucleotide similarity analysis resulted in two primary groups comprising the dog and bat antigenic variants and showing the distinct endemic cycles maintained in the different animal species in this region.  相似文献   
49.
Pharmacists and travel advice for tropics in Lisbon (Portugal)     
Teodósio R  Gonçalves L  Imperatori E  Atouguia J 《Journal of travel medicine》2006,13(5):281-287
BACKGROUND: In Portugal, little is known about the quality of advice given to international travelers by pharmacists. The aim of this study was to determine pharmacists' training, experience, and interest in travel medicine and to assess the technical quality of the information given. METHODS: We sent a postal questionnaire to all pharmacies in the Lisbon area. The technical director or another graduate pharmacist was asked to complete the questionnaire. RESULTS: A total of 251 pharmacists participated in the study. Most of them (93.2%) did not have any training in travel medicine, and most of them expressed a wish to be informed and/or updated on this subject. The number of advised travelers was low. The use of repellent, protective clothes, and mosquito bed nets was the most frequent advice on protection against mosquito bites. From a subgroup of 170 pharmacists, 43.5% indicated mefloquine and 44.1% indicated chloroquine as malaria chemoprophylaxis to African countries. A significant association existed between the variables "to indicate mefloquine" and "seeks to be informed/updated on travel medicine." Those who indicated chloroquine tended to like travel medicine less. Concerning diarrhea prevention and treatment, the consumption of bottled and/or treated water and the administration of antibiotics during the episode were the most reported advice. Concerning vaccination against yellow fever, only 8 of 91 pharmacists correctly indicated all Portuguese-speaking countries with and without the risk of this disease. CONCLUSIONS: Studied pharmacists need training in travel medicine. Travel advice was incomplete and/or incorrect and must be improved.  相似文献   
50.
History and perspectives of nurses' organization in union movements     
dos Santos RM  Trezza MC  Barros Wde O  Leite JL 《Revista brasileira de enfermagem》2006,59(1):89-94
This article presents a reflection about the history of nurses' organization in union movements just like the Central Unica dos Trabalhadores--CUT (Workers Central Union) and its perspectives for the future. The objective is to clarify the presenting ways for the union movements at present time. Primary sources for reflections was CUT's documentation. The approach considers a retrospective of CUT movement in Brazil, discussing its constituting principles. The workers union reformation was also approached, inquiring if the ways to follow in current conjuncture are respecting these principles and assuming the defense of workers' rights. This union movement defended the independence of political party, focusing nursing union as well as the National Federation of Nurses, pointing out perspectives and suggesting discussing issues and linkages to the general fight of Brazilian workers.  相似文献   
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