Cases and distribution of visceral leishmaniasis in western São Paulo: A neglected disease in this region of Brazil.

Visceral leishmaniasis (VL) is one of the most prevalent parasitic diseases worldwide. In 2019, 97% of the total numbers of cases in Latin America were reported in Brazil. In São Paulo state, currently 17.6% of infected individuals live in the western region. To study this neglected disease on a regional scale, we describe the spread of VL in 45 municipalities of the Regional Network for Health Assistance11(RNHA11). Environmental, human VL (HVL), and canine VL (CVL) cases, Human Development Index, and Lutzomyia longipalpis databases were obtained from public agencies. Global Moran's I index and local indicators of spatial association (LISA) statistics were used to identify spatial autocorrelation and to generate maps for the identification of VL clusters. On a local scale, we determined the spread of VL in the city of Teodoro Sampaio, part of the Pontal of Paranapanema. In Teodoro Sampaio, monthly peri-domicile sand fly collection; ELISA, IFAT and Rapid Test serological CVL; and ELISA HVL serum surveys were carried out. In RNHA11 from 2000 to 2018, Lu. longipalpis was found in 77.8%, CVL in 69%, and HVL in 42.2% of the 45 municipalities, and 537 individuals were notified with HVL. Dispersion occurred from the epicenter in the north to Teodoro Sampaio, in the south, where Lu. longipalpis and CVL were found in 2010, HVL in 2018, and critical hotspots of CVL were found in the periphery. Moran's Global Index showed a weak but statistically significant spatial autocorrelation related to cases of CVL (I = 0.2572), and 11 municipalities were identified as priority areas for implementing surveillance and control actions. In RNHA11, a complex array of socioeconomic and environmental factors may be fueling the epidemic and sustaining endemic transmission of VL, adding to the study of a neglected disease in a region of São Paulo, Brazil.

Influence of spermatozoal lipidomic profile on the cryoresistance of frozen spermatozoa from stallions.

The membrane of spermatozoa, which contributes to cellular cryoresistance, contains numerous lipids with a composition that directly affects membrane fluidity and the fertilization process. In light of variations in the degree of sensitivity in equine seminal freezing, this study aimed to correlate equine semen lipids with post-thawing characteristics of spermatozoa. We used ejaculates from 34 stallions, which were evaluated (total motility ≥ 60%), frozen and thawed and reevaluated for motility of spermatozoa, membrane integrity and lipid peroxidation. Lipid extraction of the fresh semen samples was performed by liquid-liquid extraction, and fingerprinting lipid analysis was conducted by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Based on the characteristics of spermatozoa after thawing, the animals could be separated into two groups: resistant (Good Freezers, n = 5) and sensitive (Bad Freezers, n = 6) to freezing, and their MALDI-MS data were then compared. The Good Freezers group showed a higher abundance of phosphatidylcholines (m/z 796.6, 846.6, 810.6, 854.6 and 732.6). The ions of m/z 812.6, 832.6, 836.6 and 838.6 belonging to the phosphatidylcholine lipid class were also positively correlated with motility of spermatozoa, whereas that of m/z 794.6 was negatively correlated with lipid peroxidation in thawed semen. The Bad Freezer group, displayed higher abundance of one phosphatidylcholines (m/z 806.6), as well as a sphingomyelins (m/z 703.5), which were negatively correlated (univariate analysis) with kinetics of spermatozoa after thawing (m/z 703.5) and with membrane integrity (m/z 792.6). The ion of m/z 717.5, assigned to phosphatidic acid, was negatively correlated with lipid peroxidation. In general therefore, the phosphatidylcholines are associated with higher quality of spermatozoa after thawing, especially in functional capacity, and that lipid semen composition was found to influence the resistance of spermatozoa to cryopreservation and may interfere with motility, membrane integrity and lipid peroxidation in stallions.

Overexpression of Hypoxia-Inducible Factor-1α in Primary Graft Dysfunction Developing in an Orthotopic Lung Transplantation Rat Model.

BACKGROUND: Primary graft dysfunction (PGD) is the major cause of early morbidity and mortality after transplantation. A high rate of PGD is a frequent complication in orthotopic lung transplantation (OLT) models, which are currently used to investigate acute and chronic rejection pathways. Hypoxia-inducible factor (HIF)-1α is a heterodimeric αß transcription factor that mediates tissue response to hypoxia. In other solid organ transplantations, a significant correlation between HIF-1α expression and PGD was detected. To our knowledge no data are available on HIF-1α expression in PGD developing in lung transplantation. The aims of this study were to investigate HIF-1α expression (using immunohistochemistry) and correlate it to the main histological parameters related to ischemia-reperfusion (IR) injury, including terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) -positive apoptotic cells). METHODS: OLT was performed in 32 inbred rat strains and 11 of them died in the early postoperative period (from day 0-3) for IR injury. The histological and molecular evaluations were done in all lung tissues. Unimplanted donor rat lungs were used as controls. HIF-1α expression was correlated with all morphological parameters. RESULTS: Lung samples of animals with IR injury showed high scores of HIF-1α expression, edema, blood extravasation, granulocyte margination, apoptotic index, and necrosis in 91% of cases. Tissue overexpression of HIF-1α was detected in all lung samples with high scores of histological parameters and with high apoptotic indexes. CONCLUSION: Our data demonstrate that HIF-1α was overexpressed in more severe rat lung IR injury. The use of HIF-1α inhibitors could provide a translatable route into manipulating this complex system in vivo.

PEGylation of coenzyme Q10 and in vitro release studies.

Methoxy polyethylene glycol conjugated with coenzyme Q10 (mPEG)-CoQ10 and analog adducts with amino acids as spacers were synthesized as a new drug delivery systems for CoQ10. Alanine and branched chain amino acids (valine, leucine and isoleucine) were conjugated to mPEG by an amide linkage and to CoQ10 by an ester bond. Recently, branched chain amino acids (BCAAs), which are released along with CoQ10, have received increasing attention as 'anti-fatigue' elements. FT-IR and 1H NMR spectroscopic analysis were useful to characterize the synthesized conjugates. Studies in vitro, in buffer solutions at different pH and in the presence of esterase were conducted. The hydrolysis studies showed a specific cleavage dependent on the pH of the medium and by the presence of proteolytic enzymes. The results showed the improvement of the pharmacokinetic properties of CoQ10. The antioxidant activity of the synthesized conjugates was also evaluated by DPPH assay.

Lipid composition of the canine sperm plasma membrane as markers of sperm motility.

The fatty acid composition of the sperm membrane is an important factor involved in the overall sperm quality, including motility. However, in the canine species, the exact composition of the plasma membrane is still unknown. Therefore, the purpose of this study was to evaluate the plasma membrane lipid composition of motile sperm cells and to compare it with asthenospermic samples, as an attempt to determine possible involvements of membrane lipids in dog sperm cell motility. The sperm-rich fraction of ten mature dogs was collected, and samples were subjected to density gradient centrifugation by Percoll® , in order to separate motile and asthenospermic samples. Processed semen samples were evaluated for sperm motility, plasma and acrosome membrane integrity, mitochondrial activity and susceptibility to oxidative stress. Lipid plasma membrane composition was identified by mass spectrometry (MALDI-MS). The motile sperm samples presented the following phospholipids in a high frequency in the plasma membrane: phosphatidylcholine 38:4 (composed of stearic and arachidonic fatty acids), phosphatidylcholine 36:1 (stearic and oleic fatty acids), phosphatidylethanolamine 34:4 (myristic and arachidonic fatty acids), glycerophosphatidic acid 36:4 (palmitic and arachidonic fatty acids), phosphatidylcholine 40:4 plasmanyl and phosphatidylcholine 40:5 plasmenyl. Furthermore, no lipid markers were found in the asthenospermic samples. Results also indicate that differences on plasma membrane composition between motile and asthenospermic samples are crucial factors for determining sperm motility, sperm functionality and susceptibility to oxidative stress. In conclusion, plasma membrane lipid composition varies considerable between motile and asthenospermic samples. Therefore, lipid markers of sperm motility can be considered, such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylcholine plasmanyl, phosphatidylcholine plasmenyl and phosphatidic acid.

Lipid profiles of canine spermatozoa as revealed via matrix-assisted laser desorption/ionization mass spectrometry.

In this study, we investigated the ability of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to characterize the lipid contents of canine spermatozoa. For that, samples of pure semen were analysed. Indeed, quite comprehensive lipid coverage was observed, and the most abundant phospholipid ions detected were from four phosphatidylcholines, that is those of m/z 760.6; 782.6; 808.6; and 830.6 and one of m/z 725.6 from a sphingomyelin. In conclusion, MALDI-MS was found to offer an easy, fast, accurate, and sensitive analytical method for lipid profiling in canine spermatozoa and could be used as a tool to select sires by assessing the relationship between sperm lipid profiles and variables such as age and breeding history as well as to study the effects of cryopreservation on lipid contents.

Epidemiology of human immunodeficiency virus-visceral leishmaniasis-co-infection.

In Brazil, the rates of mother-to-child-transmission (MTCT) of human immunodeficiency virus (HIV) decreased from 20% to 1-2% in some regions. However, the country contains 90% of individuals infected with visceral leishmaniasis (VL) in Latin America, and the west region of São Paulo state faces an alarming expansion of the disease. We describe the epidemiological aspects of the expanding infection of VL and a case report of an HIV-VL-co-infected child from the west region of São Paulo state. The patient was an AIDS-C3 with low levels of CD4, high viral load, severe diarrhea, oral and perineal candidiasis, severe thrombocytopenia, and protein-caloric malnourishment. She evolved with sepsis, renal and cardiac failure. An rK rapid diagnosis test, indirect fluorescent antibody test (IFAT), and bone marrow aspirate were performed for VL. Her symptoms improved significantly after liposomal amphotericin B administration. From the 45 municipalities that compose the Regional Health Department of Presidente Prudente, Lutzomyia longipalpis vectors were found in 58% of them. VL infected dogs were found in 33% of those municipalities, infected dogs and humans were found in 29%, 20% are starting and 33% of the municipalities are preparing VL investigation. It is likely, in this patient, that VL advanced the clinical progression of the HIV disease and the development of AIDS severity. Supported by favorable conditions, the region becomes a new frontier of VL in Brazil.

Antimycobacterial activity of N1-[1-[3-aryl-1-(pyridin-2-, 3- or 4-yl)-3-oxo] propyl]-2-pyridinecarboxamidrazones.

Infections caused by non-tuberculous mycobacteria and multidrug-resistant Mycobacterium tuberculosis are difficult to treat, and so new compounds potentially active against these bacteria are being sought. A series of 2-pyridinecarboxamidrazone derivatives, recently synthesized, have been evaluated for their inhibitory activity against 17 Mycobacterium avium isolates; the agar dilution method showed different degrees of susceptibility to the new molecules. Four molecules, three of which are chlorine derivatives, inhibited 94% of the strains tested with an MIC of 32 mg/L. These data indicate that these new pyridine-2-carboxamidrazones merit further study as antimycobacterial agents.

Synthesis and antimycobacterial activity of [5-(pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid arylidene-hydrazide derivatives.

[5-(Pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid arylidene-hydrazide derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed a feable activity against a strain of Mycobacterium tuberculosis and a strain of Mycobacterium avium.

Synthesis and antimycobacterial activity of 5-aryl-1-isonicotinoyl-3-(pyridin-2-yl)-4, 5-dihydro-1H-pyrazole derivatives.

5-Aryl-1-isonicotinoyl-3-(pyridin-2-yl)-4,5-dihydro-1H-pyrazole derivatives were synthesized and tested for their in vitro antimycobacterial activity. The compounds showed an interesting activity against a strain of Mycobacterium tuberculosis and a human strain of M. tuberculosis H4.

Synthesis and antimycobacterial activity of some 4H-1,2,4-triazin-5-one derivatives.

6-[(Arylmethylenamino)carbonyl]-3-(pyridin-2-yl)-4H-1,2,4-triazin-5-one derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed interesting activity against a strain of Mycobacterium tuberculosis.