Doenças de felinos domésticos diagnosticadas no sul do Rio Grande do Sul: estudo de 40 anos / Domestic feline diseases diagnosed in southern Rio Grande do Sul: a 40-year study

O objetivo deste estudo foi identificar as principais doenças de felinos na região sul do Rio Grande do Sul. Foram revisados os protocolos de necropsia e das amostras biológicas de felinos encaminhados ao Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas (LRD/UFPel), no período de 1978 a 2018. Nesse período foram recebidas 1633 amostras de felinos, sendo 363 (22%) entre os anos de 1978 e 1999 e 1270 (78%) entre os anos de 2000 e 2018. Com relação aos diagnósticos, 457 felinos (28%) apresentaram tumores benignos ou malignos, sendo os tegumentares e os mamários os mais frequentes. As doenças bacterianas, fúngicas, virais, parasitárias, sem agente definido e as intoxicações totalizaram 554 casos (33,9%), destacando-se a esporotricose, com 12,8% dos diagnósticos. Concluiu-se que, na região sul do RS, o encaminhamento de felinos para diagnóstico aumentou significativamente após o ano 2000, comprovando que a espécie passou a ter maior importância como animal de companhia. Concluiu-se, também, que as neoplasias têm papel relevante entre as doenças de felinos e que a esporotricose é uma das mais importantes zoonoses na região.(AU)

The goal of this paper was to identify the main disease affecting felines in the southern region of Rio Grande do Sul. The necropsy protocols and feline biological materials submitted to the Regional Diagnostic Laboratory of the Veterinary College of the Federal University of Pelotas (LRD / UFPel) were reviewed, from 1978 to 2018. During this period 1633 feline samples were received, 363 (22%) between 1978 and 1999 and 1270 (78%) between 2000 and 2018. 59% of felines did not present a defined breed. As for diagnoses, 457 felines (28%) presented benign or malignant tumors, the most common being the integumentary and mammary tumors. Bacterial, fungal, viral, parasitic or undefined agent infections and intoxications were observed in 554 cases (33.9%), especially sporotrichosis with 12.8 % of the diagnoses. It was concluded that in southern RS the referral of cats for diagnosis increased significantly after the year 2000, proving that they became more significant as companion animals. It was also concluded that neoplasia play a relevant role among feline diseases, and that sporotrichosis is one of the most important zoonoses in the region.(AU)

Comparison of perinatal outcomes between spontaneous vs. commissioned cycles in gestational carriers for single and same-sex male intended parents.

PURPOSE: To determine whether gestational carrier (GC) in vitro fertilization (IVF) cycles (commissioned cycles) for same-sex or single male intended parents have an increased incidence of adverse perinatal outcomes compared with spontaneous cycles in the same GCs. DESIGN: GC singleton pregnancies were identified from a database of 895 commissioned cycles from a large fertility center. Of these, 78 commissioned cycles met inclusion and exclusion criteria and were compared with 71 spontaneous cycles by the same GCs. The primary outcome was the composite score for adverse perinatal outcomes. Secondary outcomes included mode of delivery, birthweight, and gestational age. Chi-square test of association and Mann-Whitney U tests were used to compare categorical and continuous variables between the cohorts, respectively. Logistic and linear regressions controlling for GC age were constructed to determine the influence of GC cycle type on adverse perinatal outcomes. RESULTS: Commissioned cycles were significantly associated with adverse perinatal outcomes (25.6% vs. 9.9%; p = 0.02) and lower average gestational age (38.7 ± 1.5 vs. 39.4 ± 0.9; p < 0.001) compared with spontaneous cycles. Commissioned cycle increased the likelihood of adverse perinatal outcomes (OR 3.3; p = 0.03) and was a significant independent predictor of a lower average gestational age (ß = 0.897; p < 0.001). There were no significant differences in the incidence of vaginal deliveries or cesarean sections between commissioned and spontaneous cycles. CONCLUSIONS: Commissioned cycles confer a greater incidence of composite perinatal complications and were independently associated with a lower average gestational age when compared with spontaneous pregnancies carried by the same GC despite a confirmed healthy uterine environment, sperm samples, and donor oocytes.

Spinal cord stimulation for the management of pain: Recommendations for best clinical practice.

Spinal cord stimulation (SCS) is an accepted method of pain control. SCS has been used for many years and is supported by a substantial evidence base. A multidisciplinary consensus group has been convened to create a guideline for the implementation and execution of an SCS programme for South Africa (SA). This article discusses the evidence and appropriate context of SCS delivery, and makes recommendations for patient selection and appropriate use. The consensus group has also described the possible complications following SCS. This guideline includes a literature review and a summary of controlled clinical trials of SCS. The group notes that, in SA, SCS is performed mainly for painful neuropathies, failed back surgery, and chronic regional pain syndrome. It was noted that SCS is used to treat other conditions such as angina pectoris and ischaemic conditions, which have therefore been included in this guideline. These recommendations give guidance to practitioners delivering this treatment, to those who may wish to refer patients for SCS, and to those who care for patients with stimulators in situ. The recommendations also provide a resource for organisations that fund SCS. This guideline has drawn on the guidelines recently published by the British Pain Society, and parts of which have been reproduced with the society's permission. These recommendations have been produced by a consensus group of relevant healthcare professionals. Opinion from outside the consensus group has been incorporated through consultation with representatives of all groups for whom these recommendations have relevance. The recommendations refer to the current body of evidence relating to SCS. The consensus group wishes to acknowledge and thank the task team of the British Pain Society for their help and input into this document.

Clinical practice guidelines for management of neuropathic pain: expert panel recommendations for South Africa.

Neuropathic pain (NeuP) is challenging to diagnose and manage, despite ongoing improved understanding of the underlying mechanisms. Many patients do not respond satisfactorily to existing treatments. There are no published guidelines for diagnosis or management of NeuP in South Africa. A multidisciplinary expert panel critically reviewed available evidence to provide consensus recommendations for diagnosis and management of NeuP in South Africa. Following accurate diagnosis of NeuP, pregabalin, gabapentin, low-dose tricyclic antidepressants (e.g. amitriptyline) and serotonin norepinephrine reuptake inhibitors (duloxetine and venlafaxine) are all recommended as first-line options for the treatment of peripheral NeuP. If the response is insufficient after 2 - 4 weeks, the recommended next step is to switch to a different class, or combine different classes of agent. Opioids should be reserved for use later in the treatment pathway, if switching drugs and combination therapy fails. For central NeuP, pregabalin or amitriptyline are recommended as first-line agents. Companion treatments (cognitive behavioural therapy and physical therapy) should be administered as part of a multidisciplinary approach. Dorsal root entry zone rhizotomy (DREZ) is not recommended to treat NeuP. Given the large population of HIV/AIDS patients in South Africa, and the paucity of positive efficacy data for its management, research in the form of randomised controlled trials in painful HIV-associated sensory neuropathy (HIV-SN) must be prioritised in this country.

Intracellular developmental timers.

One of the most poorly understood aspects of animal development is how the timing of developmental events is controlled. In most vertebrate cell lineages, for example, precursor cells divide a limited number of times before they stop and terminally differentiate, but it is not known what controls when the cells stop dividing and differentiate. There is increasing evidence, however, that intracellular timers play an important part. Such cell-intrinsic timers are examples of intracellular developmental programs that change precursor cells over time. My colleagues and I have studied such intracellular timers and programs in rodent oligodendrocyte precursor cells (OPCs), as reviewed here.

The mystery of intracellular developmental programmes and timers.

There has been a revolution in understanding animal development in the last 25 years or so, but there is at least one area of development that has been relatively neglected and therefore remains largely mysterious. This is the intracellular programmes and timers that run in developing precursor cells and change the cells over time. The molecular mechanisms underlying these programmes are largely unknown. My colleagues and I have studied such programmes in two types of rodent neural precursor cells: those that give rise to oligodendrocytes, which make myelin in the CNS (central nervous system), and those that give rise to the various cell types in the retina.

Multiple fetal anomalies associated with subtle subtelomeric chromosomal rearrangements.

We report two cases of multiple fetal anomalies detected by prenatal ultrasound and associated with subtle subtelomeric chromosomal rearrangements. The first case presented at 25 weeks of gestation with an enlarged cisterna magna and ventriculomegaly. Karyotyping of amniocytes showed a subtle terminal abnormality of chromosome 6q. Thereafter, screening of all unique chromosomal subtelomeric regions using a panel of telomere-specific, fluorescence in situ hybridization (FISH) probes revealed an unbalanced reciprocal translocation between 6q and 17p [46,XX.ish der(6)t(6;17)(q25.3;p13)(TelVysion6q-;TelVysion17p+)]. The second case presented at 25 weeks of gestation with tetralogy of Fallot and at 34 weeks of gestation had additional ultrasound findings of an arachnoid cyst and intrauterine growth restriction. Postnatal karyotyping of peripheral blood was performed and appeared normal. However, a cryptic deletion of the subtelomeric region of the long arm of chromosome 14 was identified when the infant's blood sample was used as a control for an oncology FISH probe. Thereafter, screening of all unique chromosomal subtelomeric regions using a panel of telomere-specific FISH probes revealed an unbalanced reciprocal translocation of chromosomes 14q and 20p [46,XY.ish der(14)t(14;20)(q32.3;p13)(IGH-, D14S308-,TelVysion20p+)mat]. These two cases add to a growing number of reports of cryptic subtelomeric chromosomal rearrangements associated with congenital anomalies. This is the first report of multiple, simultaneous FISH screening of the subtelomeric regions in amniotic fluid and has demonstrated the technical feasibility of this technique in the prenatal period.

An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism.

BACKGROUND: Simple epithelia encase developing embryos and organs. Although these epithelia consist of only one or two layers of cells, they must provide tight barriers for the tissues that they envelop. Apoptosis occurring within these simple epithelia could compromise this barrier. How, then, does an epithelium remove apoptotic cells without disrupting its function as a barrier? RESULTS: We show that apoptotic cells are extruded from a simple epithelium by the concerted contraction of their neighbors. A ring of actin and myosin forms both within the apoptotic cell and in the cells surrounding it, and contraction of the ring formed in the live neighbors is required for apoptotic cell extrusion, as injection of a Rho GTPase inhibitor into these cells completely blocks extrusion. Addition of apoptotic MDCK cells to an intact monolayer induces the formation of actin cables in the cells contacted, suggesting that the signal to form the cable comes from the dying cell. The signal is produced very early in the apoptotic process, before procaspase activation, cell shrinkage, or phosphatidylserine exposure. Remarkably, electrical resistance studies show that epithelial barrier function is maintained, even when large numbers of dying cells are being extruded. CONCLUSIONS: We propose that apoptotic cell extrusion is important for the preservation of epithelial barrier function during cell death. Our results suggest that an early signal from the dying cell activates Rho in live neighbors to extrude the apoptotic cell out of the epithelium.

Extracellular control of cell size.

Both cell growth (cell mass increase) and progression through the cell division cycle are required for sustained cell proliferation. Proliferating cells in culture tend to double in mass before each division, but it is not known how growth and division rates are co-ordinated to ensure that cell size is maintained. The prevailing view is that coordination is achieved because cell growth is rate-limiting for cell-cycle progression. Here, we challenge this view. We have investigated the relationship between cell growth and cell-cycle progression in purified rat Schwann cells, using two extracellular signal proteins that are known to influence these cells. We find that glial growth factor (GGF) can stimulate cell-cycle progression without promoting cell growth. We have used this restricted action of GGF to show that, for cultured Schwann cells, cell growth rate alone does not determine the rate of cell-cycle progression and that cell size at division is variable and depends on the concentrations of extracellular signal proteins that stimulate cell-cycle progression, cell growth, or both.

Two molecularly distinct intracellular pathways to oligodendrocyte differentiation: role of a p53 family protein.

Both thyroid hormone (TH) and retinoic acid (RA) induce purified rat oligodendrocyte precursor cells in culture to stop division and differentiate. We show that these responses are blocked by the expression of a dominant-negative form of p53. Moreover, both TH and RA cause a transient, immediate early increase in the same 8 out of 13 mRNAs encoding intracellular cell cycle regulators and gene regulatory proteins, but only if protein synthesis is inhibited. Platelet-derived growth factor (PDGF) withdrawal also induces these cells to differentiate, but we show that the intracellular mechanisms involved are different from those involved in the hormone responses: the changes in cell cycle regulators differ, and the differentiation induced by PDGF withdrawal (or that which occurs spontaneously in the presence of PDGF) is not blocked by the dominant-negative p53. These results suggest that TH and RA activate the same intracellular pathway leading to oligodendrocyte differentiation, and that this pathway depends on a p53 family protein. Differentiation that occurs independently of TH and RA apparently involves a different pathway. It is likely that both pathways operate in vivo.

Timing cell-cycle exit and differentiation in oligodendrocyte development.

During animal development many cells permanently stop dividing and terminally differentiate. For the most part, the mechanisms that control when the cells exit the cell cycle and differentiate are not known. We have been studying the mechanisms in the oligodendrocyte cell lineage. Studies of oligodendrocyte precursor cells (OPCs) in culture suggest that each OPC has a built-in timing mechanism that helps determine when the cell stops dividing and differentiates. This intrinsic timer consists of at least two components--a timing component, which measures elapsed time, and an effector component, which stops cell division and initiates differentiation at the appropriate time. The timer seems to involve both transcriptional and posttranscriptional mechanisms, with some proteins progressively increasing and others progressively decreasing over time.

Asymmetric segregation of Numb in retinal development and the influence of the pigmented epithelium.

Asymmetric segregation of cell-fate determinants during cytokinesis plays an important part in controlling cell-fate choice in invertebrates. During Drosophila neurogenesis, for example, asymmetric segregation of the Numb protein, which inhibits Notch signaling, is necessary for the two daughter cells of a division to have different fates. In vertebrates, the role of asymmetric segregation of cell-fate determinants is uncertain, and the way the process might be regulated is unknown. We have studied the orientation of cell divisions and the distribution of Numb in the developing rat retina. We show that, whereas most retinal neuroepithelial cells divide with their mitotic spindles oriented parallel to the plane of the neuroepithelium, a substantial minority divides with their spindles oriented perpendicularly. The proportion of these vertically dividing cells changes during development, peaking around the day of birth. Numb appears to be inherited only by the apical daughter cell when a neuroepithelial cell divides vertically. Similarly, in dissociated cell cultures, some retinal neuroepithelial cells divide asymmetrically and distribute Numb to only one of the two daughter cells, suggesting that the dissociated cells can retain their polarity in vitro. Using retinal explant cultures, we find that the retinal pigment epithelium apparently promotes vertical divisions in the neural retina. To our knowledge, this is the first evidence that asymmetric segregation of cell-fate determinants may contribute to cell diversification in the mammalian retina and that an epithelium controls this process by influencing the plane of division in the adjacent neural retina.

Role of thyroid hormone receptors in timing oligodendrocyte differentiation.

The timing of oligodendrocyte differentiation is thought to depend on both intracellular mechanisms and extracellular signals. Thyroid hormone (TH) helps control this timing both in vitro and in vivo, but it is still uncertain how it does so. TH acts through nuclear receptors that are encoded by two genes, TRalpha and TRbeta. Previous studies suggested that TRbeta receptors may mediate the effect of TH on oligodendrocyte precursor cells (OPCs). Consistent with this possibility, we show here that overexpression of TRbeta1 promotes precocious oligodendrocyte differentiation, whereas expression of two dominant-negative forms of TRbeta1 greatly delays differentiation. Surprisingly, however, we find that postnatal TRbeta-/- mice have a normal number of oligodendrocytes in their optic nerves and that TRbeta-/- OPCs stop dividing and differentiate normally in response to TH in vitro. Moreover, we find that OPCs do not express TRbeta1 or TRbeta2 mRNAs, whereas they do express TRalpha1 and TRalpha2 mRNAs. These findings suggest that alpha receptors mediate the effect of TH on the timing of oligodendrocyte differentiation. We also show that TRalpha2 mRNA, which encodes a dominant-negative form of TRalpha, decreases as OPCs proliferate in vitro and in vivo. This decrease may help control when oligodendrocyte precursors differentiate.

Lack of replicative senescence in cultured rat oligodendrocyte precursor cells.

Most mammalian somatic cells are thought to have a limited proliferative capacity because they permanently stop dividing after a finite number of divisions in culture, a state termed replicative cell senescence. Here we show that most oligodendrocyte precursor cells purified from postnatal rat optic nerve can proliferate indefinitely in serum-free culture if prevented from differentiating; various cell cycle-inhibitory proteins increase, but the cells do not stop dividing. The cells maintain high telomerase activity and p53- and Rb-dependent cell cycle checkpoint responses, and serum or genotoxic drugs induce them to acquire a senescence-like phenotype. Our findings suggest that some normal rodent precursor cells have an unlimited proliferative capacity if cultured in conditions that avoid both differentiation and the activation of checkpoint responses that arrest the cell cycle.

Evidence that axon-derived neuregulin promotes oligodendrocyte survival in the developing rat optic nerve.

It was previously shown that newly formed oligodendrocytes depend on axons for their survival, but the nature of the axon-derived survival signal(s) remained unknown. We show here that neuregulin (NRG) supports the survival of purified oligodendrocytes and aged oligodendrocyte precursor cells (OPCs) but not of young OPCs. We demonstrate that axons promote the survival of purified oligodendrocytes and that this effect is inhibited if NRG is neutralized. In the developing rat optic nerve, we provide evidence that delivery of NRG decreases both normal oligodendrocyte death and the extra oligodendrocyte death induced by nerve transection, whereas neutralization of endogenous NRG increases the normal death. These results suggest that NRG is an axon-associated survival signal for developing oligodendrocytes.

Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells.

During animal development, cells become progressively more restricted in the cell types to which they can give rise. In the central nervous system (CNS), for example, multipotential stem cells produce various kinds of specified precursors that divide a limited number of times before they terminally differentiate into either neurons or glial cells. We show here that certain extracellular signals can induce oligodendrocyte precursor cells to revert to multipotential neural stem cells, which can self-renew and give rise to neurons and astrocytes, as well as to oligodendrocytes. Thus, these precursor cells have greater developmental potential than previously thought.

Partial COL1A2 gene duplication produces features of osteogenesis imperfecta and Ehlers-Danlos syndrome type VII.

Type I collagen is the most abundant structural protein in the mammalian body. It exists as a heterotrimer of two subunits in the form [alpha1(I)]2alpha2(I). Pathogenic mutations in COL1A1 and COL1A2, the genes that encode the two subunits, cause a range of phenotypes including mild to lethal forms of osteogenesis imperfecta and a restricted set of Ehlers-Danlos syndrome phenotypes. Lethal mutations usually result from missense mutations that disrupt the normal triple helical structure of the molecule. Multi-exon duplication or deletion in type I collagen genes has rarely been observed and has generally resulted in a lethal or severe phenotype. We report a partial duplication in the COLIA2 gene that causes a relatively mild phenotype, despite the addition of 477 amino acids to the triple helical domain of the proalpha2(I) chain. The abnormal molecule is synthesized and secreted by cultured dermal fibroblasts in a normal fashion. Electron microscopy of dermal tissue reveals small but otherwise near normal collagen fibrils. The gene duplication occurred by mitotic sister chromatid exchange in the mother who is mosaic for the duplication allele. Examination of the abnormal sequence suggests a means by which the duplicated molecule could be processed and properly incorporated into mature collagen fibrils.

Differences between the clearance of apoptotic cells by professional and non-professional phagocytes.

Both professional and non-professional phagocytes [1] participate in clearing the massive numbers of cells that undergo apoptosis during animal development [2], but it is not known how they divide this task. Using time-lapse recordings of cells in culture, we show that professional phagocytes (brain macrophages or microglia) are highly motile, ingest apoptotic cells immediately, and digest them quickly. Non-professionals such as BHK and lens epithelial cells are sessile, often recognize apoptotic cells as soon as they die by showing characteristic palpating movements, but delay ingestion until several hours later. By pre-ageing apoptotic cells, we show that this delay is because the apoptotic cells must undergo further changes before non-professionals can ingest them. The difference was also apparent in vivo, using immunofluorescence and electron microscopy of the developing central nervous system. This arrangement favours prompt clearance by professionals if present in adequate numbers; if they are scarce, however, non-professional bystanders will reluctantly clear the apoptotic cells.

Basic helix-loop-helix proteins and the timing of oligodendrocyte differentiation.

An intracellular timer in oligodendrocyte precursor cells is thought to help control the timing of their differentiation. We show here that the expression of the Hes5 and Mash1 genes, which encode neural-specific bHLH proteins, decrease and increase, respectively, in these cells with a time course expected if the proteins are part of the timer. We show that enforced expression of Hes5 in purified precursor cells strongly inhibits the normal increase in the thyroid hormone receptor protein TR(&bgr;)1, which is thought to be part of the timing mechanism; it also strongly inhibits the differentiation induced by either mitogen withdrawal or thyroid hormone treatment. Enforced expression of Mash1, by contrast, somewhat accelerates the increase in TR(beta)1 protein. These findings suggest that Hes5 and Mash1 may be part of the cell-intrinsic timer in the precursor cells.

The Id4 HLH protein and the timing of oligodendrocyte differentiation.

An intracellular timer is thought to help control the timing of oligodendrocyte differentiation. We show here that the expression of the helix-loop-helix gene Id4 in oligodendrocyte precursor cells decreases in vivo and in vitro with a time course expected if Id4 is part of the timer. We also show that Id4 expression decreases prematurely when the precursor cells are induced to differentiate by mitogen withdrawal. Both Id4 mRNA and protein decrease together under all of these conditions, suggesting that the control of Id4 expression is transcriptional. Finally, we show that enforced expression of Id4 stimulates cell proliferation and blocks differentiation induced by either mitogen withdrawal or treatment with thyroid hormone. These findings suggest that a progressive fall in Id4 transcription is part of the intracellular timer that helps determine when oligodendrocyte precursor cells withdraw from the cell cycle and differentiate.