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1.
J Endocrinol Invest ; 46(10): 2115-2124, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36966469

ABSTRACT

PURPOSE: To investigate the accuracy of cutoff values of the morning serum cortisol (MSC) using the cortisol stimulus test (CST) insulin tolerance test (ITT) and 250 mcg short Synacthen test (SST) as the reference standard tests, to better define its clinical role as a tool in the diagnostic investigation of adrenal insufficiency (AI) AI. METHODS: An observational study was conducted with a retrospective analysis of MSC in adult patients who had been submitted to a CST to investigate AI between January 2014 and December 2020. The normal cortisol response (NR) to stimulation was defined based on the cortisol assay. RESULTS: 371 patients underwent CST for suspected AI, 121/371 patients (32.6%) were diagnosed with AI. ROC curve analysis showed an area under the curve (AUC) for MSC of 0.75 (95% CI 0.69 - 0.80). The best MSC cutoff values to confirm AI were < 3.65, < 2.35 and < 1.5 mcg/dL with specificity of 98%, 99%, and 100%, respectively. MSC > 12.35, > 14.2 and > 14.5 mcg/dL had sensitivity of 98%, 99%, and 100%, respectively, being the best cutoff values to exclude AI. Almost 25% of patients undergoing CST for possible AI had MSC values between < 3.65 mcg/dL (6.7% of patients) and > 12.35 mcg/dL (17.5% of patients), making the formal CST testing unnecessary if we consider these cutoff values. CONCLUSION: With the most modern cortisol assays, MSC could be used as a diagnostic tool, with high accuracy to confirm or exclude AI, avoiding unnecessary CST; thus, reducing expenses and safety risks during AI investigation.


Subject(s)
Adrenal Insufficiency , Hydrocortisone , Adult , Humans , Retrospective Studies , Adrenal Insufficiency/diagnosis , ROC Curve , Time Factors
2.
Hum Reprod ; 37(6): 1334-1350, 2022 05 30.
Article in English | MEDLINE | ID: mdl-35413094

ABSTRACT

STUDY QUESTION: Could whole-exome sequencing (WES) be useful in clinical practice for men with maturation arrest (MA) after a first testicular sperm extraction (TESE)? SUMMARY ANSWER: WES in combination with TESE yields substantial additional information and may potentially be added as a test to predict a negative outcome of a recurrent TESE in patients with MA. WHAT IS KNOWN ALREADY: At present, the only definitive contraindications for TESE in men with non-obstructive azoospermia (NOA) are a 46,XX karyotype and microdeletions in the azoospermia factor a (AZFa) and/or AZFb regions. After a first negative TESE with MA, no test currently exists to predict a negative outcome of a recurrent TESE. STUDY DESIGN, SIZE, DURATION: In a cohort study, we retrospectively included 26 patients with idiopathic NOA caused by complete MA diagnosed after a first TESE. PARTICIPANTS/MATERIALS, SETTING, METHODS: Twenty-six men with MA at the spermatocyte stage in all seminiferous tubules, according to a histopathological analysis performed independently by two expert histologists, and a normal karyotype (i.e. no AZF gene microdeletions on the Y chromosome) were included. Single-nucleotide polymorphism comparative genomic hybridization array and WES were carried out. The results were validated with Sanger sequencing. For all the variants thought to influence spermatogenesis, we used immunohistochemical techniques to analyse the level of the altered protein. MAIN RESULTS AND THE ROLE OF CHANCE: Deleterious homozygous variants were identified in all seven consanguineous patients and in three of the 19 non-consanguineous patients. Compound heterozygous variants were identified in another 5 of the 19 non-consanguineous patients. No recurrent variants were identified. We found new variants in genes known to be involved in azoospermia or MA [including testis expressed 11 (TEX11), meiotic double-stranded break formation protein 1 (MEI1), proteasome 26s subunit, ATPase 3 interacting protein (PSMC3IP), synaptonemal complex central element protein 1 (SYCE1) and Fanconi anaemia complementation group M (FANCM) and variants in genes not previously linked to human MA (including CCCTC-binding factor like (CTCFL), Mov10 like RISC complex RNA helicase 1 (MOV10L1), chromosome 11 open reading frame 80 (C11ORF80) and exonuclease 1 (EXO1)]. LARGE SCALE DATA: Data available on request. LIMITATIONS, REASONS FOR CAUTION: More data are required before WES screening can be used to avoid recurrent TESE, although screening should be recommended for men with a consanguineous family background. WES is still a complex technology and can generate incidental findings. WIDER IMPLICATIONS OF THE FINDINGS: Our results confirmed the genetic aetiology of MA in most patients: the proportion of individuals with at least one pathologic variant was 50% in the overall study population and 100% in the consanguineous patients. With the exception of MEI1 (compound heterozygous variants of which were identified in two cases), each variant corresponded to a specific gene-confirming the high degree of genetic heterogeneity in men with MA. Our results suggest that WES screening could help to avoid recurrent, futile TESE in men with MA in general and in consanguineous individuals in particular, but these results need to be confirmed in future studies before clinical implementation. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Fondation Maladies Rares (Paris, France), Merck (Kenilworth, NJ, USA), IRSF (Montigny le Bretonneux, France) and Agence de la Biomédecine (Saint Denis, France). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Azoospermia , Azoospermia/diagnosis , Azoospermia/genetics , Azoospermia/pathology , Cohort Studies , Comparative Genomic Hybridization , DNA Helicases , DNA-Binding Proteins/genetics , Humans , Male , Nuclear Proteins/genetics , RNA Helicases , Retrospective Studies , Sperm Retrieval , Spermatozoa/pathology , Testis/pathology , Trans-Activators , Exome Sequencing
3.
Epidemiol Infect ; 148: e288, 2020 12 01.
Article in English | MEDLINE | ID: mdl-33256878

ABSTRACT

This study aimed to analyse the spatial-temporal distribution of COVID-19 mortality in Sergipe, Northeast, Brazil. It was an ecological study utilising spatiotemporal analysis techniques that included all deaths confirmed by COVID-19 in Sergipe, from 2 April to 14 June 2020. Mortality rates were calculated per 100 000 inhabitants and the temporal trends were analysed using a segmented log-linear model. For spatial analysis, the Kernel estimator was used and the crude mortality rates were smoothed by the empirical Bayesian method. The space-time prospective scan statistics applied the Poisson's probability distribution model. There were 391 COVID-19 registered deaths, with the majority among ⩾60 years old (62%) and males (53%). The most prevalent comorbidities were hypertension (40%), diabetes (31%) and cardiovascular disease (15%). An increasing mortality trend across the state was observed, with a higher increase in the countryside. An active spatiotemporal cluster of mortality comprising the metropolitan area and neighbouring cities was identified. The trend of COVID-19 mortality in Sergipe was increasing and the spatial distribution of deaths was heterogeneous with progression towards the countryside. Therefore, the use of spatial analysis techniques may contribute to surveillance and control of COVID-19 pandemic.


Subject(s)
COVID-19/mortality , Age Factors , Aged , Bayes Theorem , Brazil/epidemiology , COVID-19/complications , Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , Cities , Cluster Analysis , Comorbidity , Diabetes Complications/epidemiology , Educational Status , Female , Humans , Hypertension/complications , Hypertension/epidemiology , Linear Models , Male , Middle Aged , Monte Carlo Method , Race Factors , Risk Factors , Rural Health , Sex Factors , Spatial Analysis , Spatio-Temporal Analysis , Time Factors
4.
Epidemiol Infect ; 148: e188, 2020 08 24.
Article in English | MEDLINE | ID: mdl-32829732

ABSTRACT

This study aimed to analyse the trend and spatial-temporal clusters of risk of transmission of COVID-19 in northeastern Brazil. We conducted an ecological study using spatial and temporal trend analysis. All confirmed cases of COVID-19 in the Northeast region of Brazil were included, from 7 March to 22 May 2020. We used the segmented log-linear regression model to assess time trends, and the local empirical Bayesian estimator, the global and local Moran indexes for spatial analysis. The prospective space-time scan statistic was performed using the Poisson probability distribution model. There were 113 951 confirmed cases of COVID-19. The average incidence rate was 199.73 cases/100 000 inhabitants. We observed an increasing trend in the incidence rate in all states. Spatial autocorrelation was reported in metropolitan areas, and 178 municipalities were considered a priority, especially in the states of Ceará and Maranhão. We identified 11 spatiotemporal clusters of COVID-19 cases; the primary cluster included 70 municipalities from Ceará state. COVID-19 epidemic is increasing rapidly throughout the Northeast region of Brazil, with dispersion towards countryside. It was identified high risk clusters for COVID-19, especially in the coastal side.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Spatio-Temporal Analysis , Betacoronavirus , Brazil/epidemiology , COVID-19 , Cities , Humans , Linear Models , Pandemics , SARS-CoV-2
5.
Zygote ; 28(1): 32-36, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31601279

ABSTRACT

The present study evaluated the effect of knockout serum replacement (KSR), fetal bovine serum (FBS) and bovine serum albumin (BSA) on the viability and growth of bovine secondary follicles cultured in vitro for 12 days. To this end, secondary follicles were isolated (185-202 µm) and cultured in vitro in TCM-199+ medium supplemented with KSR (5% and 10%), FBS (5% and 10%) or BSA (3 mg/ml) at 38.5°C with 5% CO2 in air. Follicular diameters were evaluated on days 0, 4, 8 and 12. After 12 days of culture, follicular survival analysis was performing by using calcein-AM and ethidium homodimer. Before and after culture, follicles were fixed in paraformaldehyde for histological evaluation. Follicular diameter at different days of culture were compared using the Kruskal-Wallis test, while the percentages of viable follicles were analyzed by chi-squared test (P < 0.05). Results showed that follicles cultured in the presence of KSR at both concentrations presented higher follicular survival rates than those cultured in control medium alone or supplemented with FBS or BSA. Conversely, the presence of KSR, BSA or FBS did not increase follicular diameter after 12 days of culture. Histology analysis showed that, among the tested treatments, follicles cultured in the presence of KSR had preserved rounded oocytes, juxtaposed granulosa cells and intact basal membrane. In conclusion, supplementation of culture medium with KSR increases the follicular survival of bovine secondary follicles cultured in vitro.


Subject(s)
Culture Media/pharmacology , In Vitro Oocyte Maturation Techniques , Oocytes/cytology , Ovarian Follicle/cytology , Proteins/administration & dosage , Serum Albumin, Bovine/administration & dosage , Animals , Cattle , Female , Granulosa Cells/cytology , Granulosa Cells/drug effects , Granulosa Cells/metabolism , Oocytes/drug effects , Oocytes/metabolism , Ovarian Follicle/drug effects , Ovarian Follicle/metabolism
6.
Zygote ; 28(6): 504-510, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32847639

ABSTRACT

This study aimed to evaluate the effects of dexamethasone on development, viability, antrum formation and ultrastructural integrity of bovine secondary follicles cultured in vitro for 18 days. Bovine ovaries were obtained from slaughterhouses and secondary follicles of ~150-200 µm diameter were isolated and cultured in the laboratory in TCM-199+ alone or supplemented with different concentrations of dexamethasone (1, 10, 100 and 1000 ng/ml). Follicle viability was evaluated after the culture period, using calcein-AM (viable) and ethidium homodimer (nonviable). Follicle diameters and antrum formation were evaluated at days 0, 6, 12 and 18. Before or after in vitro culture, follicles were fixed for histological and ultrastructural analysis. Follicle diameters were evaluated using analysis of variance and Kruskal-Wallis test, while chi-squared test was used to evaluate the percentage of viable follicles and antrum formation (P < 0.05). Follicles cultured for 6 days with all treatments increased their diameters significantly, but there was no significant difference between treatments at the end of the culture period. In vitro cultured follicles showed antral cavity formation at the end of the culture period, but no influence of dexamethasone was seen. Ultrastructural analysis showed that follicles cultured with dexamethasone (1, 10, 100 and 1000 ng/ml) had well preserved granulosa cells. However, oocytes from follicles cultured with 10, 100 or 1000 ng/ml dexamethasone showed signs of degeneration. It can be concluded that follicles cultured in vitro in the presence of dexamethasone demonstrated continuous in vitro growth, but oocytes from follicles cultured with 10, 100 or 1000 ng/ml dexamethasone had poor ultrastructure.


Subject(s)
Ovarian Follicle , Animals , Cattle , Dexamethasone , Female , Granulosa Cells , Oocytes , Tissue Culture Techniques
7.
Cryo Letters ; 41(6): 365-370, 2020.
Article in English | MEDLINE | ID: mdl-33990814

ABSTRACT

BACKGROUND: Semen cryopreservation is essential in animal breeding programs for improving the availability of genetic resources from animals with high breeding value. OBJECTIVE: To evaluate the addition of Brazil nut extract as a replacement for egg yolk in bovine semen cryopreservation. MATERIALS AND METHODS: Semen was collected from five Nelore bulls and cryopreserved with the addition (treatments) of 0, 25, 50, 75, or 100% Brazil nut extract in the cryoprotectant medium. After thawing, spermatic cells were evaluated for morphology, plasma membrane integrity, spermatic kinetics, and in vitro fertilization. The experimental design was in randomized blocks, and the data were submitted to regression analysis. RESULTS: The minor-type and total defects, and plasma membrane integrity were affected (P < 0.05) as a function of egg yolk substitution with Brazil nut extract. There was a significant effect (P < 0.05) of Brazil nut extract addition on the spermatic kinetics and cleavage rate. CONCLUSION: The addition of Brazil nut extract in the cryoprotective medium as a substitute of egg yolk for freezing bovine semen negatively affects sperm quality and fertility.


Subject(s)
Bertholletia/chemistry , Cryopreservation/veterinary , Cryoprotective Agents , Plant Extracts , Semen Preservation , Animals , Cattle , Cryoprotective Agents/pharmacology , Egg Yolk , Male , Plant Breeding , Plant Extracts/pharmacology , Semen , Semen Analysis , Semen Preservation/veterinary , Sperm Motility , Spermatozoa
8.
J Helminthol ; 94: e122, 2020 Jan 22.
Article in English | MEDLINE | ID: mdl-31964430

ABSTRACT

Eurytrema coelomaticum is a digenean flatworm of ruminants that is the causative agent of eurytrematosis, a disease of veterinary health concern. Although modern techniques of morphological analysis have provided new insights about the morphology and anatomy of parasitic helminths, most studies on E. coelomaticum adults are based on conventional light microscopy. In the present study, a combined approach using brightfield, fluorescence, confocal and scanning electron microscopies (SEMs), together with the cryofracture technique, have updated morphological data on E. coelomaticum recovered from cattle in Rio de Janeiro State, Brazil. Light microscopy confirmed the presence of several structures present in the current description, such as suckers, pharynx, oesophagus, intestinal bifurcation and the cirrus-sac. Fluorescence stereomicroscopy revealed for the first time the cubic crystal protein inclusions in the forebody, which were further detailed by confocal and SEMs. Confocal microscopy provided detailed information of the muscular architecture associated with the attachment structures (suckers), digestive system (pharynx and oesophagus), egg-forming complex (ovary, Mehlis' gland and Laurer's canal) and male reproductive system, which are similar to those found in other digenean flukes. SEM images of cryofractured parasites showed mucus and developing eggs within uterine loops. It was demonstrated that the combination of advanced tools generated complementary information, confirming the importance of experimental morphology in parasitology. Therefore, the knowledge of the adult structural organization of E. coelomaticum was improved and this work has contributed to propose new morphological criteria to evaluate the effects of antiparasitic drugs on flukes of medical and veterinary importance.


Subject(s)
Heterophyidae/anatomy & histology , Heterophyidae/ultrastructure , Animals , Cattle , Cattle Diseases/parasitology , Eggs , Female , Genitalia/anatomy & histology , Genitalia/ultrastructure , Male , Microscopy, Confocal , Microscopy, Electron, Scanning , Platyhelminths , Trematode Infections/veterinary
9.
Med Oral Patol Oral Cir Bucal ; 24(3): e281-e289, 2019 May 01.
Article in English | MEDLINE | ID: mdl-31011137

ABSTRACT

BACKGROUND: The present study aimed to measure the impact of oral health on the quality of life of patients with head and neck cancer. MATERIAL AND METHODS: A cross-sectional study was conducted with 130 patients diagnosed with head and neck cancer at two medical centers. Participants answered a sociodemographic questionnaire and the Oral Health Impact Profile - 14 (OHIP-14). Clinical aspects, cancer staging, and treatment approach were also investigated. Mann-Whitney and Kruskal-Wallis non-parametric tests were used for statistical analysis, followed by Poisson regression analysis (with robust error variance), to associate the OHIP-14 scores with independent variables. RESULTS: The OHIP-14 presented good internal consistency (Cronbach's Alpha = 0.861). The mean score obtained was 19.52 (±11.79). Physical pain (3.70±2.44), physical disability (3.26±2.62) and functional limitation (3.24±2.45) were ranked as the main factors affecting the quality of life. Patients non-Caucasians (PR = 1.30; IC 95% = 1.07-1.58; p = 0.009), widowers (PR = 1.36; IC 95% = 1.13-1.64; p = 0.001), diagnosed with squamous cell carcinoma (PR = 1.28; IC 95% = 1.05-1.58; p = 0.017) and with temporomandibular pain (PR = 1.31; IC 95% = 1.08-1.60; p = 0.007) were more likely to exhibit lower rates of quality of life. CONCLUSIONS: The results showed a high impact of the oral health in the quality of life of patients with head and neck cancer was observed. Sociodemographic and clinical characteristics can exert influence on the quality of life of patients with head and neck cancer.


Subject(s)
Head and Neck Neoplasms , Quality of Life , Cross-Sectional Studies , Humans , Oral Health , Surveys and Questionnaires
10.
Trop Anim Health Prod ; 51(3): 735, 2019 03.
Article in English | MEDLINE | ID: mdl-30617723

ABSTRACT

The original version of this article unfortunately contains an error. Vanessa do Nascimento Ramos was not included in the original article as one of the contributors. The name is now included in the authorgroup.

11.
J Neuroinflammation ; 15(1): 230, 2018 Aug 14.
Article in English | MEDLINE | ID: mdl-30107848

ABSTRACT

BACKGROUND: Treatment of spinal cord injury is dependent on neuronal survival, appropriate synaptic circuit preservation, and inflammatory environment management. In this sense, mesenchymal stem cell (MSC) therapy is a promising tool that can reduce glial reaction and provide trophic factors to lesioned neurons. METHODS: Lewis adult female rats were submitted to a unilateral ventral funiculus cut at the spinal levels L4, L5, and L6. The animals were divided into the following groups: IA (intramedullary axotomy), IA + DMEM (Dulbecco's modified Eagle's medium), IA + FS (fibrin sealant), IA + MSC (106 cells), and IA + FS + MSC (106 cells). Seven days after injury, qPCR (n = 5) was performed to assess gene expression of VEGF, BDNF, iNOS2, arginase-1, TNF-α, IL-1ß, IL-6, IL-10, IL-4, IL-13, and TGF-ß. The cellular infiltrate at the lesion site was analyzed by hematoxylin-eosin (HE) staining and immunohistochemistry (IH) for Iba1 (microglia and macrophage marker) and arginase-1. Fourteen days after injury, spinal alpha motor neurons (MNs), evidenced by Nissl staining (n = 5), were counted. For the analysis of astrogliosis in spinal lamina IX and synaptic detachment around lesioned motor neurons (GAP-43-positive cells), anti-GFAP and anti-synaptophysin immunohistochemistry (n = 5) was performed, respectively. Twenty-eight days after IA, the gait of the animals was evaluated by the walking track test (CatWalk; n = 7). RESULTS: The site of injury displayed strong monocyte infiltration, containing arginase-1-expressing macrophages. The FS-treated group showed upregulation of iNOS2, arginase-1, proinflammatory cytokine (TNF-α and IL-1ß), and antiinflammatory cytokine (IL-10, IL-4, and IL-13) expression. Thus, FS enhanced early macrophage recruitment and proinflammatory cytokine expression, which accelerated inflammation. Rats treated with MSCs displayed high BDNF-positive immunolabeling, suggesting local delivery of this neurotrophin to lesioned motoneurons. This BDNF expression may have contributed to the increased neuronal survival and synapse preservation and decreased astrogliosis observed 14 days after injury. At 28 days after lesion, gait recovery was significantly improved in MSC-treated animals compared to that in the other groups. CONCLUSIONS: Overall, the present data demonstrate that MSC therapy is neuroprotective and, when associated with a FS, shifts the immune response to a proinflammatory profile.


Subject(s)
Cell- and Tissue-Based Therapy/methods , Gene Expression Regulation/physiology , Immunomodulation/physiology , Mesenchymal Stem Cells/physiology , Motor Neurons/metabolism , Neuroprotection/physiology , Spinal Cord Injuries , Animals , Arginase/genetics , Arginase/metabolism , Axotomy/methods , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Female , Fibrin Tissue Adhesive/therapeutic use , RNA, Messenger/metabolism , Rats , Rats, Inbred Lew , Spinal Cord Injuries/complications , Spinal Cord Injuries/pathology , Spinal Cord Injuries/therapy , Tissue Adhesives/therapeutic use , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism
12.
J Nanosci Nanotechnol ; 18(10): 6746-6755, 2018 10 01.
Article in English | MEDLINE | ID: mdl-29954490

ABSTRACT

Nanostructured materials have been widely studied aiming to biomedical applications, primarily for the purpose of carrying drugs or molecules of interest in a selected tissue or organ. In this context, boron nitride nanotubes (BNNTs), when functionalized with specific moieties, could be useful as nanovectors for delivery of proteins, drugs, and also RNAi molecules, due to their capacity to be uptaked by cells. The introduction of magnetic nanoparticles allows the use of such system as a hyperthermia agent. Thus, once it has been targeted to tumor areas, it could kill cancer cells by magnetohyperthermia therapy. In order to study this effect, magnetite nanoparticles were incorporated into hydroxilated BNNT. The system was characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and vibrating sample magnetometry (VSM). The results obtained show that magnetite nanoparticles are linked to the nanotubes. Magnetic measurements show that coercivity and magnetization were not disturbed after incorporation to the BNNT. Based on this, a new methodology for in vitro magnetohyperthermia experiments was developed, aiming to treat each cell group individually preserving its sterility. The biological assays of the system demonstrate its good cell viability and the great potential of this nanomaterial as a magnetohyperthermia agent for cancer treatment.


Subject(s)
Boron Compounds/therapeutic use , Hyperthermia, Induced , Magnetic Field Therapy , Magnetite Nanoparticles/therapeutic use , Neoplasms/therapy , Boron Compounds/chemistry , Cell Survival , Humans , Hyperthermia, Induced/methods , Magnetic Field Therapy/methods , Magnetite Nanoparticles/chemistry , Nanomedicine , Nanotubes/chemistry
13.
J Helminthol ; 92(4): 514-519, 2018 Jul.
Article in English | MEDLINE | ID: mdl-28780915

ABSTRACT

A new species of the genus Diomedenema, a spiruromorph nematode, collected from the lung of Spheniscus magellanicus (Sphenisciformes) found on the southern coast of the state of Rio Grande do Sul, Brazil, is described. The new species is differentiated from the only previously described species of the genus, D. diomedeae Johston & Mawson, 1952, by males possessing a set of caudal papillae with three pairs of precloacal, two pairs of adcloacal and one pair of postcloacal papillae; precloacal papillae with the papillae of the first two pairs being closer to each other than those of the third pair; a longer and pointed tail in males; and females with the vulva at mid-body. This is the first report of a nematode infecting the lung of a sphenisciforme host.


Subject(s)
Bird Diseases/parasitology , Rhabditida Infections/veterinary , Rhabditida/isolation & purification , Spheniscidae/parasitology , Animals , Brazil , Female , Male , Rhabditida/classification , Rhabditida/genetics , Rhabditida/growth & development , Rhabditida Infections/parasitology
14.
Trop Anim Health Prod ; 49(3): 555-559, 2017 03.
Article in English | MEDLINE | ID: mdl-28124730

ABSTRACT

Leptospirosis is a zoonotic disease of world importance, and its transmission depends on the interaction between humans and animals. Given the necessity to investigate potential hosts of Leptospira spp., this study verified the prevalence of different serovars in the species of Rhipidomys spp., a widespread sigmodont rodent in Brazil. The studied population originates from a semi-evergreen forest located in the county of Uberlândia, in the state of Minas Gerais. The microscopic agglutination test (MAT) was performed with 14 serovars. Thirteen out of the 43 wild rodents captured showed a positive agglutination reaction, with a greater prevalence of the serovars Pyrogenes, Copenhageni, and Canicola. This study found a prevalence of 30.3% anti-Leptospira spp. antibodies; all positive animals were reactive to more than one serovar.


Subject(s)
Antibodies, Bacterial/blood , Leptospira/immunology , Leptospirosis/veterinary , Rodent Diseases/epidemiology , Agglutination Tests/veterinary , Animals , Arvicolinae , Brazil/epidemiology , Forests , Leptospirosis/epidemiology , Prevalence , Risk Factors , Rodent Diseases/blood , Rodent Diseases/microbiology , Tropical Climate , Zoonoses/epidemiology
15.
Drug Chem Toxicol ; 39(1): 28-34, 2016.
Article in English | MEDLINE | ID: mdl-25690107

ABSTRACT

Amphotericin B is the "gold standard" agent in the management of serious systemic fungal infections. However, this drug can cause nephrotoxicity, which contributes up to 25% of all acute kidney injuries in critically ill patients. Cyclic adenosine monophosphate can protect kidney cells from death due to injury or drug exposure in some cases. Hence, the objective of this work was to evaluate if cAMP could prevent cell death that occurs in renal cell lines subjected to AmB treatment and, if so, to assess the involvement of PKA in the transduction of this signal. Two different renal cell lines (LLC-PK1 and MDCK) were used in this study. MTT and flow cytometry assays showed increased cell survival when cells were exposed to cAMP in a PKA-independent manner, which was confirmed by western blot. This finding suggests that cAMP (db-cAMP) may prevent cell death caused by exposure to AmB. This is the first time this effect has been identified when renal cells are exposed to AmB's nephrotoxic potential.


Subject(s)
Amphotericin B/toxicity , Antifungal Agents/toxicity , Cyclic AMP/administration & dosage , Kidney/drug effects , Animals , Blotting, Western , Cell Survival/drug effects , Cyclic AMP/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Dogs , Flow Cytometry , Kidney/pathology , LLC-PK1 Cells , Madin Darby Canine Kidney Cells , Signal Transduction/drug effects , Swine
16.
Clin Genet ; 85(3): 233-44, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23489061

ABSTRACT

Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be characterized by karyotype. In many prenatal cases of de novo sSMC, the outcome of pregnancy is difficult to predict because the euchromatin content is unclear. This study aimed to determine the presence or absence of euchromatin material of 39 de novo prenatally ascertained sSMC by array-comparative genomic hybridization (array-CGH) or single nucleotide polymorphism (SNP) array. Cases were prospectively ascertained from the study of 65,000 prenatal samples [0.060%; 95% confidence interval (CI), 0.042-0.082]. Array-CGH showed that 22 markers were derived from non-acrocentric markers (56.4%) and 7 from acrocentic markers (18%). The 10 additional cases remained unidentified (25.6%), but 7 of 10 could be further identified using fluorescence in situ hybridization; 69% of de novo sSMC contained euchromatin material, 95.4% of which for non-acrocentric markers. Some sSMC containing euchromatin had a normal phenotype (31% for non-acrocentric and 75% for acrocentric markers). Statistical differences between normal and abnormal phenotypes were shown for the size of the euchromatin material (more or less than 1 Mb, p = 0.0006) and number of genes (more or less than 10, p = 0.0009). This study is the largest to date and shows the utility of array-CGH or SNP array in the detection and characterization of de novo sSMC in a prenatal context.


Subject(s)
Chromosome Aberrations , Genetic Counseling , Genetic Predisposition to Disease , Prognosis , Adult , Comparative Genomic Hybridization , Female , France , Genetic Association Studies , Genetic Markers , Genome-Wide Association Study , Humans , In Situ Hybridization, Fluorescence , Karyotype , Middle Aged , Polymorphism, Single Nucleotide , Pregnancy , Prenatal Diagnosis , Prospective Studies , Risk , Switzerland , Young Adult
17.
Prenat Diagn ; 34(5): 424-30, 2014 May.
Article in English | MEDLINE | ID: mdl-24395195

ABSTRACT

OBJECTIVE: The 22q11.2 deletion (del22q11.2) is one of the most common microdeletions. We performed a collaborative, retrospective analysis in France of prenatal diagnoses and outcomes of fetuses carrying the del22q11.2. METHODS: A total of 272 fetuses were included. Data on prenatal diagnosis, ultrasound findings, pathological features, outcomes and inheritance were analyzed. RESULTS: The mean time of prenatal diagnosis was 25.6 ± 6 weeks of gestation. Most of the diagnoses (86.8%) were prompted by abnormal ultrasound findings [heart defects (HDs), in 83.8% of cases]. On fetal autopsy, HDs were again the most common disease feature, but thymus, kidney abnormalities and facial dysmorphism were also described. The deletion was inherited in 27% of cases. Termination of pregnancy (TOP) occurred in 68.9% of cases and did not appear to depend on the inheritance status. However, early diagnosis was associated with a higher TOP rate. CONCLUSION: This is the largest cohort of prenatal del22q11.2 diagnoses. As in postnatally diagnosed cases, HDs were the most frequently observed abnormalities. However, thymus and kidney abnormalities and polyhydramnios should also be screened for in the prenatal diagnosis of del22q11.2. Only the time of diagnosis appeared to be strongly associated with the pregnancy outcome: the earlier the diagnosis, the higher the TOP rate.


Subject(s)
Abnormalities, Multiple/diagnostic imaging , DiGeorge Syndrome/diagnosis , Pregnancy Outcome , Ultrasonography, Prenatal , Adolescent , Adult , Autopsy , DiGeorge Syndrome/epidemiology , Female , Fetus , France , Health Surveys , Humans , Middle Aged , Pregnancy , Retrospective Studies , Young Adult
18.
Andrologia ; 46(5): 576-82, 2014 Jun.
Article in English | MEDLINE | ID: mdl-23701584

ABSTRACT

Complex chromosome rearrangements (CCR) with two independent chromosome rearrangements are rare. Although CCRs lead to high unbalanced gamete rates, data on meiotic segregation in this context are scarce. A male patient was referred to our clinic as part of a family screening programme prompted by the observation of a 44,X,der(Y),t(Y;15)(q12;q10)pat,rob(13;14)(q10;q10)mat karyotype in his brother. Karyotyping identified the same CCR. Sperm FISH (with locus-specific probes for the segments involved in the translocations and nine chromosomes not involved in both rearrangements) was used to investigate the rearrangements meiotic segregation products and establish whether or not an inter-chromosomal effect was present. Sperm nuclear DNA fragmentation was also evaluated. For rob(13;14) and der(Y), the proportions of unbalanced products were, respectively, 26.4% and 60.6%. Overall, 70.3% of the meiotic segregation products were unbalanced. No evidence of an inter-chromosomal effect was found, and the sperm nuclear DNA fragmentation rate was similar to our laboratory's normal cut-off value. In view of previously published sperm FISH analyses of Robertsonian translocations (and even though the mechanism is still unknown), we hypothesise that cosegregation of der(Y) and rob(13;14) could modify rob(13;14) meiotic segregation.


Subject(s)
Chromosome Aberrations , In Situ Hybridization, Fluorescence , Spermatozoa/metabolism , Translocation, Genetic , Female , Humans , In Situ Nick-End Labeling , Karyotyping , Male , Meiosis/genetics , Pedigree
19.
Toxicol Mech Methods ; 24(6): 369-76, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24785081

ABSTRACT

Cyclosporine is an important immunosuppressive agent; however, nephrotoxicity is one of the main adverse effects. The purpose of this study was to evaluate the effect of inhibiting the protein kinase A (PKA) signaling pathway in nephrotoxicity caused by cyclosporine from the assessment of cell viability, pro-inflammatory cytokines, and nitric oxide (NO) production in LLC-PK1 and MDCK cell lines. Cyclosporine proved to be cytotoxic for both cell lines, as assessed by the mitochondrial enzyme activity assay (MTT), caused DNA fragmentation, determined by flow cytometry using the propidium iodide dye, and activated the PKA pathway (western blot assay). In MDCK cells, the inhibition of the PKA signaling pathway (H89 inhibitor) caused a significant reduction in DNA fragmentation. In both cell lines, the production of IL-6 proved to be a dependent PKA pathway, while TNF-α was not influenced by the inhibition of the PKA pathway. The NO production was increased when cells were pre-incubated with H89 followed by cyclosporine, and this production was dependent on the PKA pathway in LLC-PK1 and MDCK cells lines. Therefore, considering the present study's results, it can be concluded that the inhibition of PKA signaling pathway can aid in reducing the degree of nephrotoxicity caused by cyclosporine.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclosporine/toxicity , Kidney/drug effects , Signal Transduction/drug effects , Animals , Blotting, Western , Cell Line , Cell Survival , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/genetics , DNA Fragmentation , Dogs , Gene Expression Regulation, Enzymologic/drug effects , Immunosuppressive Agents/toxicity , Isoquinolines/pharmacology , Kidney/cytology , Nitric Oxide/metabolism , Protein Kinase Inhibitors/pharmacology , Sulfonamides/pharmacology , Swine
20.
J Occup Environ Med ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664957

ABSTRACT

OBJECTIVES: To compare the prevalence of LTBI and TB in the pre-pandemic period (2017-2019) with the pandemic period (2020-2022), in a group of HCW. METHODS: Retrospective study. Data on TB diagnosis was retrieved from the hospital information system database. All HCWs who underwent tuberculin skin test (TST) from January 2017 to December 2022 were included in the study. RESULTS: In the pre-pandemic period (2017-2019), 163 HCW out of 710 were TST positive (22.9%), and in the pandemic period (2020-2022), 85 HCW out of 449 were TST positive (18.9%) (p = 0.11). There were 10 HCW diagnosed with TB in the pre-pandemic period (incidence: 41.7/100,000) and 2 in the pandemic period (incidence: 8.3/100,000) (p < 0.0001). CONCLUSIONS: This study showed that TB incidence was reduced during the pandemic period in HCW. TST positivity was also reduced, although not statistically significant.

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