Neurobiology of anesthetic-surgical stress and induced behavioral changes in dogs and cats: A review.

The anesthetic-surgical stress response consists of metabolic, neuroendocrine, hemodynamic, immunological, and behavioral adaptations through chemical mediators such as the adrenocorticotropic hormone, growth hormone, antidiuretic hormone, cortisol, aldosterone, angiotensin II, thyroid-stimulating hormone, thyroxine, triiodothyronine, follicle-stimulating hormone, luteinizing hormone, catecholamines, insulin, interleukin (IL)-1, IL-6, tumor necrosis factor-alpha, and prostaglandin E-2. Behavioral changes include adopting the so-called prayer posture, altered facial expressions, hyporexia or anorexia, drowsiness, sleep disorders, restriction of movement, licking or biting the injured area, and vocalizations. Overall, these changes are essential mechanisms to counteract harmful stimuli. However, if uncontrolled surgical stress persists, recovery time may be prolonged, along with increased susceptibility to infections in the post-operative period. This review discusses the neurobiology and most relevant organic responses to pain and anesthetic-surgical stress in dogs and cats. It highlights the role of stress biomarkers and their influence on autonomous and demeanor aspects and emphasizes the importance of understanding and correlating all factors to provide a more accurate assessment of pain and animal welfare in dogs and cats throughout the surgical process.

Nociceptive pain and anxiety in equines: Physiological and behavioral alterations.

Pain and anxiety are two of the most important concerns in clinical veterinary medicine because they arise as consequences of multiple factors that can severely affect animal welfare. The aim of the present review was to provide a description and interpretation of the physiological and behavioral alterations associated with pain and anxiety in equines. To this end, we conducted an extensive review of diverse sources on the topic. The article begins by describing the neurophysiological pathway of pain, followed by a discussion of the importance of the limbic system in responses to pain and anxiety, since prolonged exposure to situations that cause stress and pain generates such physiological changes as tachycardia, tachypnea, hypertension, hyperthermia, and heart rate variability (HRV), often accompanied by altered emotional states, deficient rest, and even aggressiveness. In the long term, animals may show deficiencies in their ability to deal with changes in the environment due to alterations in the functioning of their immune, nervous, and endocrinologic systems. In conclusion, pain and anxiety directly impact the homeostasis of organisms, so it is necessary to conduct objective evaluations of both sensations using behavioral scales, like the horse grimace scale, complemented by assessments of blood biomarkers to analyze their correlation with physiological parameters: Heart rate, respiratory rate, HRV, theparasympathetic tone activity index, lactate and glucose levels, and temperature. Additional tools - infrared thermography, for example - can also be used in these efforts to improve the quality of life and welfare of horses.

Cardiorespiratory effects of epidurally administered ketamine or lidocaine in dogs undergoing ovariohysterectomy surgery: a comparative study.

BACKGROUND: Analgesic and hemodynamic effects of ketamine in subanesthetic doses during surgical anesthesia and postoperative, are due to the action on the N-methyl-D-aspartate receptors (NMDAR). AIMS: To evaluate the intraoperative cardiorespiratory effects provided by ketamine compared to lidocaine, both administered epidurally, in bitches submitted to ovariohysterectomy. METHODS: Thirty-six dogs of different breeds were used in a randomized, prospective, and blinded clinical trial. Two groups were formed: GKET (ketamine 3 mg/kg, n=18) and GLIDO (lidocaine 4 mg/kg, n=18). Animals were premedicated with acepromazine 0.05 mg/kg intravenous. Anesthesia was induced with propofol 5 mg/kg intravenous. Anesthetic maintenance was performed with isoflurane in 100% oxygen. Every 5 min during surgery, heart rate (HR), respiratory rate (RR), esophageal temperature (°C), oxygen saturation (SPO2), end tidal carbon dioxide (ETCO2) and mean arterial pressure (MAP) were monitored. RESULTS: Cardiorespiratory variables during anesthesia were within normal ranges. Heart rate was significantly higher at 5 (108 ± 12 vs 95 ± 11) and 10 (110 ± 11 vs 97 ± 11) min in GKET compared to GLIDO after the start of surgery (P=0.03 and P=0.01, respectively). Mean arterial pressure was higher in GKET, (100 ± 23, 105 ± 35, and 103 ± 35 mmHg) in comparison with GLIDO (66 ± 7, 74 ± 10, and 67 ± 9 mmHg) at 20, 25 and 30 min (P=0.01, P=0.004, and P=0.002, respectively). Mild hypothermia at 25 (36.5 1.3C) and 30 (36.5 1.4C) min in the GKET was recorded. CONCLUSION: Epidural administration of ketamine provides better hemodynamic stability, compared to the use of epidural lidocaine.

Overexpression of connexin 43 reduces melanoma proliferative and metastatic capacity.

BACKGROUND: Alterations in connexin 43 (Cx43) expression and/or gap junction (GJ)-mediated intercellular communication are implicated in cancer pathogenesis. Herein, we have investigated the role of Cx43 in melanoma cell proliferation and apoptosis sensitivity in vitro, as well as metastatic capability and tumour growth in vivo. METHODS: Connexin 43 expression levels, GJ coupling and proliferation rates were analysed in four different human melanoma cell lines. Furthermore, tumour growth and lung metastasis of high compared with low Cx43-expressing FMS cells were evaluated in vivo using a melanoma xenograft model. RESULTS: Specific inhibition of Cx43 channel activity accelerated melanoma cell proliferation, whereas overexpression of Cx43 increased GJ coupling and reduced cell growth. Moreover, Cx43 overexpression in FMS cells increased basal and tumour necrosis factor-α-induced apoptosis and resulted in decreased melanoma tumour growth and lower number and size of metastatic foci in vivo. CONCLUSIONS: Our findings reveal an important role for Cx43 in intrinsically controlling melanoma growth, death and metastasis, and emphasise the potential use of compounds that selectively enhance Cx43 expression on melanoma in the future chemotherapy and/or immunotherapy protocols.

Oxidative stress in systemic lupus erythematosus: relationship to disease activity and symptoms.

Oxidative stress may play a role in the pathogenesis of systemic lupus erythematosus (SLE). We examined the hypothesis that oxidative stress was associated with indices of lupus disease activity and severity of symptoms. Urinary F2 isoprostane excretion, a validated marker of oxidative stress, was measured in 95 patients with SLE and 103 healthy controls. Outcome measures included SLEDAI and SLICC scores, the modified health assessment questionnaire, the fatigue severity scale (FSS), and visual analogue scales (VAS) for fatigue, pain and overall disease activity. F2 isoprostane excretion was compared in patients and controls, and its relationship with clinical variables in SLE examined. F2 isoprostane excretion did not differ significantly among patients with lupus (2.7 +/- 2.3 ng/mg Cr) and control subjects (2.2 +/- 1.4 ng/mg Cr) (P = 0.70). In patients with lupus, F2 isoprostane concentrations were independently associated with higher patient reported disease activity (VAS) (OR = 1.52, P = 0.01), fatigue (FSS, OR = 1.52, P = 0.03) and lower quality of life (OR = 0.73, P = 0.05), but not with objective markers or inflammation or disease activity. In conclusion, F2 isoprostane excretion is associated with patient-reported symptoms in SLE but not with measures of inflammation, SLEDAI or SLICC. Oxidative stress may contribute to debilitating symptoms such as fatigue in SLE.

Cardiovascular risk scores and the presence of subclinical coronary artery atherosclerosis in women with systemic lupus erythematosus.

The Framingham risk score is widely used to identify patients at increased cardiovascular risk, and women with systemic lupus erythematosus (SLE) have a marked increased prevalence of cardiovascular events. Thus, we examined the hypothesis that cardiovascular risk scores would identify women with SLE who had asymptomatic coronary atherosclerosis. Ninety-three women with SLE and 65 control subjects were studied. The Framingham score and a score for younger populations developed from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study were compared in both groups. Coronary atherosclerosis was ascertained by electron beam computed tomography. There were no significant differences in the median (interquartile range) Framingham [5 (2-10) compared to 7 (0-10), P = 0.88] and PDAY [15 (14-18) compared to 16 (13-18), P = 0.99] scores in patients with SLE and controls, respectively. Coronary atherosclerosis was associated with higher Framingham [12 (3-15) compared to 4 (1-8), P = 0.008] and PDAY [17 (15-19 compared to 15 (12-18), P = 0.03)] scores in patients with SLE; however, 99% of patients were classified as low-risk with a 10-year predicted risk of 1% (<1-3%). Our data indicate that cardiovascular risk scores are not adequate for risk stratification in women with SLE. Measurement of coronary calcification may add information to identify asymptomatic women with lupus who might benefit from aggressive preventive measures.

Persistence of vaccine-derived poliovirus following a mass vaccination campaign in Cuba: implications for stopping polio vaccination after global eradication.

BACKGROUND: With substantial progress made toward polio eradication, developing the appropriate strategy for discontinuing global oral poliovirus vaccine (OPV) after global eradication becomes increasingly important. At issue is the theoretical risk of independent circulation of potentially virulent OPV-derived strains. Because Cuba uses OPV only in mass campaigns, it represents an ideal site to assess vaccine-derived poliovirus persistence. METHODS: Infants born after the 1997 biannual mass campaigns were evaluated for past (neutralizing antibody) or current (virus excretion) evidence of vaccine-derived poliovirus exposure. We obtained sera and/or stool specimens from 861 infants; a second serum from 218 infants. RESULTS: All stool specimens were poliovirus negative. Of 762 infants, 113 (14.8%) had initially detectable poliovirus type 1 antibody, 193 (25.3%) type 2, and 94 (12.3%) type 3. A precipitous antibody decline occurred in initially positive sera. CONCLUSIONS: Our results suggest that in a country with high population immunity, vaccine-derived virus is unlikely to establish ongoing circulation.

Mechanism of enterovirus involvement in epidemic neuropathy: hypothesis regarding pathophysiology.

During the epidemic of optic and peripheral neuropathy which occurred in Cuba in 1992-1993, viruses antigenically related to the Coxsackie viruses were isolated from cerebrospinal fluid of patients. Concurrently with the virologic studies, epidemiologic, toxicologic, nutritional, immunologic, and histopathologic investigations were also carried out. Although it was demonstrated that the illness was associated with toxic and nutritional risk factors, it has not been possible to identify a specific etiology for the symptoms observed. Taking into consideration the results obtained in all of the various investigations, we have formulated an integral, multifactorial hypothesis which attempts to explain a pathophysiologic mechanism by which the viruses isolated could participate in the pathogenesis of the illness. We propose that the viral agents produce a persistent infection, and the possibility that they may act as mediator of an autoimmune pathogenic process.

[Hematometra & Listeria monocytogenes]. / Hematometra por Listeria monocytogenes.

The hematometra is a nosological entity that may not always be attributed to an embryonic defect of the paramesonefros; cervical-vaginal infections such as etiological possibilities due to Listeria monocytogenes (Lm), cervix malignant neoplasias, iatrogenias due to endometrial ablation with Lasser, traumatic bloody uterine curetage and because of cervical cryocoagulation or electrocoagulation are also mentioned. The case to be reported is from a woman in reproductive stage, who is 32 years old, and had menarca at the age of 13, starting her sexual life at 31, not using any method to control her fertility. When having an eight-week amenorrhea after 8 months of marriage, she visited the doctor for assumed pregnancy, within the prenatal analysis a pelvic echographic study was requested, finding out images that we concluded as hematometra, having been drained and demonstrated the presence of LM by anti-Lm antibodies, being administered Azitromicina and Espiramicina.

Meningoencefalitis virales por Enterovirus en Cuba en el período 1990-1995 / Viral meningoencephalities due to enteroviruses in Cuba during 1990-1995

Se describen los resultados del estudio de enterovirus como agentes causanes de meningoencefalitis viral (MEV) en Cuba, desde 1990 hasta 1995. En este período fueron estudiados 586 muestras de heces, 108 líquidos cefalorraquídeos y 1095 sueros pareados para un total de 1789 muestras, procedentes de 1458 pacientes diagnosticados clínicamente con esta patología. Las muestras para el aislamiento viral se inocularon en dos sistemas celulares diferentes, encontrándose 225 muestras positivas a enterovirus que representan el 32,42 o/o del total; el mayor número de aislamientos (217) fue a partir de heces, en células diploides de fibroblastos de pulmón humano (PHuE-1). Las determinaciones de anticuerpos se realizaron por prueba de neutralizacion en micrométodo, enfrentándolos con 10 antígenos de enterovirus (Echovirus 4, 6, 9, 11 y Coxsackievirus B1-6) y, en períodos epidémicos, además con el virus aislado. En los años estudiados se produjeron tres brotes epidémicos por Coxsackievirus A9 (1990-91), Echovirus 30 (1994) y Coxsackievirus B5 (1995). Es de señalar que desde 1970 los Coxsackievirus A9 y Echovirus 30 se vincularon en nuestro país, por primera vez, con epidemias de MEV. En los sueros pareados se obtuvo 66,84 o/o de positivos, siendo la mayor positividad a los Echovirus 6 y 11. Al considerar en conjunto la positividad por aislamiento y serología, más del 80 o/o de los casos estudiados pudieran tener ua explicación por algún enterovirus, lo uqe demuestra la importancia de estos agentes como causantes de MEV en Cuba (AU)

Meningoencefalitis virales por Enterovirus en Cuba en el período 1990-1995 / Viral meningoencephalities due to enteroviruses in Cuba during 1990-1995

Se describen los resultados del estudio de enterovirus como agentes causanes de meningoencefalitis viral (MEV) en Cuba, desde 1990 hasta 1995. En este período fueron estudiados 586 muestras de heces, 108 líquidos cefalorraquídeos y 1095 sueros pareados para un total de 1789 muestras, procedentes de 1458 pacientes diagnosticados clínicamente con esta patología. Las muestras para el aislamiento viral se inocularon en dos sistemas celulares diferentes, encontrándose 225 muestras positivas a enterovirus que representan el 32,42 o/o del total; el mayor número de aislamientos (217) fue a partir de heces, en células diploides de fibroblastos de pulmón humano (PHuE-1). Las determinaciones de anticuerpos se realizaron por prueba de neutralizacion en micrométodo, enfrentándolos con 10 antígenos de enterovirus (Echovirus 4, 6, 9, 11 y Coxsackievirus B1-6) y, en períodos epidémicos, además con el virus aislado. En los años estudiados se produjeron tres brotes epidémicos por Coxsackievirus A9 (1990-91), Echovirus 30 (1994) y Coxsackievirus B5 (1995). Es de señalar que desde 1970 los Coxsackievirus A9 y Echovirus 30 se vincularon en nuestro país, por primera vez, con epidemias de MEV. En los sueros pareados se obtuvo 66,84 o/o de positivos, siendo la mayor positividad a los Echovirus 6 y 11. Al considerar en conjunto la positividad por aislamiento y serología, más del 80 o/o de los casos estudiados pudieran tener ua explicación por algún enterovirus, lo uqe demuestra la importancia de estos agentes como causantes de MEV en Cuba

[Enterovirus meningoencephalitis in the last 5 years]. / Meningoencefalitis por Enterovirus en los últimos 5 años.

The results of the study of Enterovirus as viral meningoencephalitis producing agents, carried out from 1990 to 1994, are described, 546 feces samples, 95 cerebrospinal fluids and 1,058 matched sera were studied and obtained from 1,388 patients clinically diagnosed with this disease. Samples for viral isolation were inoculated into two different cellular systems. The highest number of isolation was found in diploid cells from human fibroblast. Antibody determinations were carried out by a neutralization test (micromethod) with 11 Enterovirus antigens (Echo 4, 6, 9, 11 and 30; and Coxsackie B1, 2, 3, 4, 5 and 6) and in epidemic periods with the isolated virus. During the years under study, 2 epidemic outbreaks took place: on caused by Coxsackie A9 (1990-1991) and the other one by Echo 30 (1994). A greater positivity to Echo 6 and 11 was found among the matched sera.

[Cuban epidemic neuropathy. III. Neutralizing antibodies to the strains isolated and to other enteroviruses in patients and healthy subjects]. / Neuropatía epidémica cubana. Parte III. Anticuerpos neutralizantes a cepas aisladas y otros Enterovirus en pacientes y personas sanas.

Determinations of neutralizing antibodies to the strain 47/93 IPK (CA9) and to the strain 590 were performed in serum samples from patients presenting with epidemic neuropathy and from a group of seemingly healthy subjects. Determinations were also done in the reference strains CA9 and CB1-6 by the microneutralization technique. Patients and their contacts showed significantly higher percentages of neutralizing antibodies to the strain 47/93 than the control group and residents of municipalities with a low rate of the disease. This difference was also confirmed regarding the geometric mean titres with the use of the reference strains CA9 and CB2-4. An increased circulation of the strain 47/93 within the infantile population from 1981 to 1993 was evidenced. Patients exhibited significantly lower percentages and geometric mean titres of neutralizing antibodies to the strain 590 than the control group, despite the fact that in 25/28 certain agents having a mild cytopathogenic effect had been isolated. The possibility of two mechanism of neutralization is stated and an hypothesis on the mechanism by which these viruses may be involved in the pathophysiology of the disease is formulated.