A Unique Combination of Male Germ Cell miRNAs Coordinates Gonocyte Differentiation

The last 100 years have seen a concerning decline in male reproductive health associated with decreased sperm production, sperm function and male fertility. Concomitantly, the incidence of defects in reproductive development, such as undescended testes, hypospadias and testicular cancer has increased. Indeed testicular cancer is now recognised as the most common malignancy in young men. Such cancers develop from the pre-invasive lesion Carcinoma in Situ (CIS), a dysfunctional precursor germ cell or gonocyte which has failed to successfully differentiate into a spermatogonium. It is therefore essential to understand the cellular transition from gonocytes to spermatogonia, in order to gain a better understanding of the aetiology of testicular germ cell tumours. MicroRNA (miRNA) are important regulators of gene expression in differentiation and development and thus highly likely to play a role in the differentiation of gonocytes. In this study we have examined the miRNA profiles of highly enriched populations of gonocytes and spermatogonia, using microarray technology. We identified seven differentially expressed miRNAs between gonocytes and spermatogonia (down-regulated: miR-293, 291a-5p, 290-5p and 294*, up-regulated: miR-136, 743a and 463*). Target prediction software identified many potential targets of several differentially expressed miRNA implicated in germ cell development, including members of the PTEN, and Wnt signalling pathways. These targets converge on the key downstream cell cycle regulator Cyclin D1, indicating that a unique combination of male germ cell miRNAs coordinate the differentiation and maintenance of pluripotency in germ cells

The Implications of Relationships between Human Diseases and Metabolic Subpathways

One of the challenging problems in the etiology of diseases is to explore the relationships between initiation and progression of diseases and abnormalities in local regions of metabolic pathways. To gain insight into such relationships, we applied the “k-clique” subpathway identification method to all disease-related gene sets. For each disease, the disease risk regions of metabolic pathways were then identified and considered as subpathways associated with the disease. We finally built a disease-metabolic subpathway network (DMSPN). Through analyses based on network biology, we found that a few subpathways, such as that of cytochrome P450, were highly connected with many diseases, and most belonged to fundamental metabolisms, suggesting that abnormalities of fundamental metabolic processes tend to cause more types of diseases. According to the categories of diseases and subpathways, we tested the clustering phenomenon of diseases and metabolic subpathways in the DMSPN. The results showed that both disease nodes and subpathway nodes displayed slight clustering phenomenon. We also tested correlations between network topology and genes within disease-related metabolic subpathways, and found that within a disease-related subpathway in the DMSPN, the ratio of disease genes and the ratio of tissue-specific genes significantly increased as the number of diseases caused by the subpathway increased. Surprisingly, the ratio of essential genes significantly decreased and the ratio of housekeeping genes remained relatively unchanged. Furthermore, the coexpression levels between disease genes and other types of genes were calculated for each subpathway in the DMSPN. The results indicated that those genes intensely influenced by disease genes, including essential genes and tissue-specific genes, might be significantly associated with the disease diversity of subpathways, suggesting that different kinds of genes within a disease-related subpathway may play significantly differential roles on the diversity of diseases caused by the corresponding subpathway

Technical and environmental performance of eggshell lime for soil stabilization

Searching for alternative materials to reduce the extraction of natural resources is key to a more sustainable world and relevant to construction and infrastructure projects in which large amounts of materials are used. Eggshell is a solid waste that is rich in calcium carbonate and can potentially replace limestone for lime production. This research examines the environmental impacts of eggshell limes and commercially available limes using Life Cycle Assessment (LCA). In addition, a physical–chemical and mineralogical characterization of eggshell limes and an assessment of the strength and stiffness of a sandy soil stabilized with ground glass and such limes are carried out. Results show that eggshell limes have reduced impacts for aquatic ecotoxicity, terrestrial ecotoxicity and land occupation when compared to traditional limes as two processes (Quarrying of limestone and Limestone improvement) are eliminated. A reduction of 65.1% in damage to Ecosystem quality was observed for eggshell quicklime (versus quicklime from limestone) and of 50% for eggshell hydrated lime (versus hydrated lime from limestone). Eggshell limes were found to have adequate physical–chemical-mineralogical characteristics for soil stabilization applications, being composed by 97.0% calcium oxide and 2.0% magnesium oxide (quicklime) and by 89.6% calcium hydroxide, 2.9% magnesium hydroxide and 5% calcium carbonate (hydrated lime). Lastly, both limes improved the strength and stiffness of the studied soil by reacting with ground glass (pozzolan)

Estudo comparativo entre estibogluconato de sódio BP 88® e antimoniato de meglumina no tratamento da leishmaniose cutânea II. Toxicidade bioquímica e cardíaca Comparative study between sodium stibogluconate BP 88®and meglumine antimoniate in cutaneous leishmaniasis treatment. II. Biochemical and cardiac toxicity

Foi avaliada a toxicidade de dois antimoniais pentavalentes em 111 pacientes com leishmaniose cutânea. Quarenta e sete pacientes receberam antimoniato de meglumina (Grupo I) e 64 pacientes, estibogluconato de sódio BP 88® (Grupo II), 20mg SbV/kg/dia por 20 dias. Realizou-se a avaliação de aminotransferases, fosfatase alcalina, amilase, creatinina, uréia, exame de urina e eletrocardiograma, antes do tratamento e no décimo e vigésimo dias. Observou-se maior freqüência de valores anormais de aminotransferases no décimo e vigésimo dias de tratamento no grupo II (p < 0,001) e maior proporção de valores anormais de amilase no décimo dia no mesmo grupo (p < 0,001). Houve maior variação dos níveis de aminotransferases, fosfatase alcalina e amilase nos primeiros dez dias no grupo II (p < 0,01). No vigésimo dia observou-se maior variação nos níveis de aminotransferases no grupo II (p = 0,02 e p = 0,03, respectivamente). Quarenta e três porcento dos pacientes do grupo I e 54% dos pacientes do grupo II apresentaram alterações eletrocardiográficas (p = 0,30).<br>Toxicity of two antimonial pentavalents were evaluated in 111 patients with cutaneous leishmaniasis. Forty seven patients received meglumine antimoniate (Group I) and 64 patients, sodium stibogluconate BP 88® (Group II), 20mg SbV/kg/day for 20 days. Evaluation of aminotransferases, alkaline phosphatase, amilase, creatinine, urea, urine analysis and electrocardiogram were performed at baseline, on the tenth and twentieth day of treatment. Greater frequency of aminotransferase abnormal levels were observed on the tenth and twentieth days in group II (p < 0,001) and a greater proportion of amilase abnormal levels at the tenth day in the same group (p < 0,001). There was a greater variation of aminotransferases, alkaline phosphatase and amilase in the first ten days of treatment in group II (p < 0,01). On the twentieth day there was a greater variation of aminotransferase levels in group II (p = 0,02 and p = 0,03, respectively). Forty three percent of group I and 54% of group II showed electrocardiographic abnormalities (p = 0,30)

Óbito durante tratamento da leishmaniose tegumentar americana com stibogluconato de sódio bp 88® (shandong xinhua) Fatal case during treatment of american tegumentary leishmaniasis with sodium stibogluconate bp 88® (shandong xinhua)

Os autores relatam a ocorrência de óbito em paciente portador da forma cutânea da LTA no município de Caxias-MA. Trata-se de paciente do sexo masculino, 22 anos, gari, portador de lesão ulcerada no membro inferior (perna esquerda), diagnosticado, após encontro do parasita (Leishmania) na lesão, tratado com stibogluconato de sódio BP88® (Shandong Xinhua) na dose de 10mg/Sb+5/kg/dia/20 dias. Após a 3ª dose apresentou dores articulares, naúseas, mal estar geral. Com a continuação da medicação houve agravamento do quadro com dor epigástrica e no hipocôndrio direito irradiando-se para o hemitórax homolateral. Após a 7ª dose apresentou dispnéia associado à dor torácica de leve intensidade. Na 9ª dose houve piora do quadro, mesmo assim continuou a usar o medicamento até a 11ª dose quando seu estado agravou-se. Foi internado, necessitando de tratamento intensivo. Nos exames realizados apresentou: 4,4 milhões de eritócitos, 10,6% de hemoglobina, 35% de hematócrito, 26.400 de leucócitos, basófilos e mielócitos (0), 59% de segmentados, 30% de linfócitos, 2% de monócitos, plaquetas (normais), glicose 42mg%, uréia 73mg%, creatinina (2,4mg%), eletrocardiograma (bloqueio de ramo direito). Veio a falecer tendo como causa do óbito, insuficiência cárdio respiratória. O relato atual mostra a necessidade de esclarecimento das equipes de saúde quanto ao uso dos Sb+5 e também lembrar o Ministério da Saúde quando da aquisição de novos produtos, preocupar-se com a qualidade e procedência do mesmo.<br>The authors report the occurrence of a fatal case in patient with cutaneous leishmaniasis in the municipality of Caxias, MA. Male patient, 22 years old, road sweeper, presented with an ulcer in left leg, diagnosed as cutaneous leishmaniasis and treated with sodium stibogluconate BP88®(Sb+5) (Shandong Xinhua) at a dose of 10mg/Sb+5/kg/day/20 days. After dose three he presented arthralgia, myalgia, nausea and weakness. During the therapy there was an aggravation of the symptoms with abdominal pain and irradiation into the thorax. After dose seven he presented a picture of associated dyspnea and thoracic pain of mild intensity. At dose nine there was further worsening of the picture, nevertheless the therapy was continued up to dose 11, when the patient's state deteriorated to such an extent that he was hospitalized in the intensive care unit. Exams: erythrocytes, 4.4 million; hemoglobin, 10.6%; hematocrits, 35%; white blood cells 26,400, basophiles and myelocytes (0); segmented leukocytes, 59%; lymphocytes 30%; monocytes 2%; platelets (normal); glucose, 42mg%; urea, 73mg%; creatinine, 2.4mg%; and ECG (blockade of right branch). The patient died from cardiorespiratory insufficiency. The current report underscores the need to clarify health workers regarding the use of Sb+5 and also to remind the Health Ministry to verify the quality and origin when acquiring new products