Monoclonal antibodies in idiopathic chronic eosinophilic pneumonia: a scoping review.

BACKGROUND: Idiopathic chronic eosinophilic pneumonia (ICEP) is a rare disease characterized by pulmonary radiological alterations, peripheral eosinophilia, and demonstrated pulmonary eosinophilia. Oral steroids (OSs) are the standard management, but relapses occur in up to 50% of patients during the decrease or suspension of steroids, usually requiring reinitiation of treatment, exposing patients to secondary events derived from the management. Management with monoclonal antibodies has been proposed in these cases to control the disease and limit the secondary effects. The objective is to describe the extent and type of evidence regarding the use of monoclonal antibodies for ICEP. METHODS: A panoramic review of the literature was performed. Observational and experimental studies of pediatric and adult populations that managed recurrent ICEP with monoclonal antibodies were included. Data search, selection, and extraction were performed by two independent reviewers. RESULTS: 937 studies were found. After applying the inclusion and exclusion criteria, 37 titles remained for the final analysis: a retrospective, observational, real-life study, two case series publications, and 34 case reports published in academic poster sessions and letters to the editor. In general, the use of monoclonal antibodies approved for severe asthma could be useful for the control of ICEP, since most of the results show a good response for clinical and radiological outcomes. Biological drugs seem to be a safer option for controlling relapses in ICEP, allowing lowering/suspension of OSs, and sometimes replacing them in patients intolerant to them, patients with significant comorbidities, and patients who have already developed adverse events. CONCLUSION: The extent of the evidence supporting management of ICEP with monoclonal antibodies against IL-5 and IgE (omalizumab) is limited, but it could be promising in patients who present frequent relapses, in cortico-dependent individuals, or in patients in whom the use of steroids is contraindicated. The extent of the evidence for management with dupilumab is more limited. Studies with better design and structure are needed to evaluate quality of life and outcomes during a clear follow-up period. To our knowledge, this is the first scoping review of the literature showing the extent of the evidence for the management of ICEP with monoclonal antibodies.

Acute phase proteins and total antioxidant capacity in free-roaming cats infected by pathogenic leptospires.

BACKGROUND: Leptospirosis is a neglected but widespread zoonotic disease throughout the world. Most mammals are hosts of Leptospira spp., including domestic cats, species in which no consensus has been reached on the clinical presentation or diagnosis of the disease. The study of acute-phase proteins (APPs) and biomarkers of oxidative status would contribute to knowledge about the disease in cats. This report evaluated four APPs: Serum amyloid A-SAA, Haptoglobin-Hp, albumin and Paraoxonase 1-PON1 and the antioxidant response through Total Antioxidant Capacity-TAC, in 32 free-roaming cats. Cats were classified as seroreactive for anti-leptospiral antibodies (group 1, n = 8), infected with Leptospira spp (group 2, n = 5) and leptospires-free cats (group 3, n = 19). RESULTS: SAA differences were observed between groups 1 and 2 (p-value = 0.01) and between groups 2 and 3 (p-value = 0.0001). Hp concentration differences were only detected between groups 2 and 3 (p-value = 0.001). Albumin concentrations only differed between groups 1 and 3 (p-value = 0.017) and 2 and 3 (p-value < 0.005). Cats in groups 1 (p-value < 0.005) and 2 (p-value < 0.005) had lower PON1 concentrations than group 3. No statistically significant differences between pairs of groups were detected for TAC concentrations. The principal component analysis (PCA) retained two principal components, (PC1 and PC2), explaining 60.1% of the observed variability of the inflammatory proteins and the antioxidant TAC. CONCLUSIONS: Increases in Serum SAA, Hp, and decreases in PON1 activity may indicate an active inflammatory state in infected cats (currently or recently infected).

Providing geriatric oncology care using telemedicine for older patients with cancer during the COVID-19 pandemic in Mexico.

The objective of this study was to describe our experience using readily available telemedicine tools to deliver specialist multidisciplinary care to older adults with cancer at a Mexican medical centre during the COVID-19 pandemic. Between March 2020 and March 2021, patients aged ≥65 years with colorectal or gastric cancer treated at a geriatric oncology clinic in Mexico City were included. Patients were reached via telemedicine utilising readily available apps such as WhatsApp or Zoom. We performed interventions such as geriatric assessments, treatment toxicity assessments, physical examinations and treatment prescription. The number of visits per patient, type of device used, preferred software/app, consultation barriers and the ability of the team to deliver complex interventions were analysed and reported. A total of 44 patients received at least one telehealth visit, with a total of 167 consultations. Only 20% of patients had webcam-equipped computers, and 50% of visits were performed using a caregiver's device. Seventy-five percent of visits took place using WhatsApp, and 23% using Zoom. The average visit lasted 23 minutes, with only 2% not completed due to technical issues. A geriatric assessment was successfully conducted in 81% of telemedicine visits, and chemotherapy was prescribed remotely in 32%. The use of telemedicine is possible in older adults with cancer living in developing countries and with little previous exposure to digital technology using readily available platforms such as WhatsApp. Healthcare centres in developing countries should make efforts to enhance the use of telemedicine, particularly for vulnerable populations such as older adults with cancer.

Effect of a geriatric unit in the outcomes of hospitalized older Mexican adults with cancer: A case-control study.

INTRODUCTION: Geriatric interventions may improve the care of hospitalized older adults with cancer, but information regarding their effect on geriatric-specific outcomes is lacking. We studied the effect of a specialized geriatrician-led inpatient geriatric management unit compared with a conventional internal medicine ward on the outcomes of hospitalized older adults with cancer in Mexico. MATERIALS AND METHODS: Case-control study including persons aged ≥65 years with solid malignancies who had a cancer-related hospitalization at a university-affiliated hospital in Mexico City. Patients hospitalized in a geriatric unit (cases) were paired 1:2 with those in internal medicine wards (controls). Matching criteria included: age (+/- five years), tumor type (according to International Classification of Diseases [ICD]-10 code), and admission date (+/- three months). The association between being hospitalized in the geriatric unit on various outcomes was determined using conditional logistic regression models. RESULTS: One hundred cases and 200 controls were included. Mean age was 75.3 years (standard deviation 6.4 years) and 53% had gastrointestinal tumors. No difference in median length-of-stay was found between cases and controls (9.0 days, vs. 9.5 days, p = 0.34). Hospitalization in the geriatric unit was associated with a reduced risk of delirium (odds ratio [OR] 0.18, 95% confidence interval [CI] 0.04-0.80). Being hospitalized in the geriatric unit was not associated with an effect on hospital-acquired complications (OR 0.83, 95% CI 0.47-1.45) or in-hospital mortality (OR 1.82, 95% CI 0.32-10.18). DISCUSSION: Among older Mexican adults hospitalized for a cancer-related diagnosis, receiving care in a geriatric management unit was associated to a decreased risk of delirium, without influencing other outcomes.

Financial Toxicity Among Older Mexican Adults With Cancer and Their Families: A Mixed-Methods Study.

PURPOSE: The financial toxicity (FT) of cancer is common among older adults in high-income countries, but little is known about the financial hardships faced by older patients with cancer living in developing countries. The aim of this study was to explore the financial burden of cancer among older Mexican adults and their relatives, as well as factors that might mitigate such burden. METHODS: This mixed-methods study included patients age 65 years and older with the 10 most common malignancies in Mexico and 3-24 months from diagnosis at two cancer centers in Mexico City and their relatives. For the quantitative component, patients and relatives answered the Spanish version of the Consumer Financial Protection Bureau Financial Well-Being Scale. Patients completed the Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) scale and a 3-month, self-reported cost diary. For the qualitative component, focused interviews were used to explore the individual experiences of patients and their relatives. RESULTS: Ninety-six patients and their relatives were included, of whom 45% had stage IV disease. On the COST-FACIT scale, 9% reported no FT, 52% mild FT, 39% moderate FT, and 0% severe FT. The mean Consumer Financial Protection Bureau Financial Well-Being Scale score was 45.2, with 78% reporting poor financial well-being (score ≤ 50). On cost diaries, most expenses were associated with purchasing medications, including chemotherapy. Focused interviews showed that most patients and relatives had to acquire debt to face costs of cancer care. CONCLUSION: A high proportion of Mexican older adults with cancer reported FT and poor financial well-being. Understanding experiences associated with FT and strategies to mitigate it represents an essential first step to design public policies aimed at protecting older adults with cancer and their families from catastrophic spending.

Reply to Detection of Leptospira interrogans DNA in Urine of a Captive Ocelot (Leopardus pardalis).

In reply to a comment, we want to mention that we consider this report significant in animal leptospirosis [...].

American Society of Clinical Oncology-Sponsored Oncology Student Interest Groups in Latin America.

PURPOSE: To describe the characteristics of the members of the ASCO-sponsored Oncology Student Interest Groups (OSIGs) in Latin America. METHODS: This was a multicenter cross-sectional study. We surveyed 97 OSIG members from three medical schools in Peru and Mexico. We administered a 60-question survey covering topics including personal background, oncology training experience, and professional practice expectations and preferences. RESULTS: A little more than one half of the surveyed OSIG members were female. More than one half had a visa to visit the United States and had an advanced level of English. One half of the OSIG members were also ASCO members. Most participants agreed or strongly agreed that participation in their OSIG increased their interest in cancer-related specialties (94%) and provided professional networking opportunities (94%) and that it was accessible to all students (91%). Most participants believed that their OSIG had sufficient resources to carry out its activities. Students were asked to rate their interest when they entered medical school versus at the time of the survey. Most of the members were strongly interested in pursuing surgical oncology. The majority of members were somewhat interested or very interested in palliative care and medical oncology. CONCLUSION: To our knowledge, this is the first study that provides data on medical student perceptions of the Latin American OSIGs sponsored by ASCO. Student perceptions of medical oncology and the impact of OSIGs were generally positive. Given the shortages of oncology specialists in Latin American and elsewhere, strategies to engage medical students in the pursuit of cancer-related careers are becoming increasingly essential.

Leptospira Detection in Cats in Spain by Serology and Molecular Techniques.

Leptospirosis is the most neglected widespread zoonosis worldwide. In Spain, leptospirosis reports in people and animals have increased lately. Cats can become infected with Leptospira, as well as be chronic carriers. The aim of this study was to determine serological antibody prevalence against Leptospira sp., blood DNA, and shedding of DNA from pathogenic Leptospira species in the urine of cats in Spain. Microagglutination tests (MAT) and blood and urine TaqMan real-time polymerase chain reaction (PCR) were performed. Leptospira antibodies were detected in 10/244 cats; with 4.1% positive results (95% confidence interval (CI): 2.1-7.18%). Titers ranged from 1:20 to 1:320 (serovars Ballum; Bataviae; Bratislava; Cynopteri; Grippotyphosa Mandemakers; Grippotyphosa Moskva; Pomona; and Proechimys). The most common serovar was Cynopteri. Blood samples from 1/89 cats amplified for Leptospira DNA (1.12%; 95% CI: 0.05-5.41%). Urine samples from 4/232 cats amplified for Leptospira DNA (1.72%; 95% CI: 0.55-4.10%). In conclusion free-roaming cats in Spain can shed pathogenic Leptospira DNA in their urine and may be a source of human infection. Serovars not previously described in cats in Spain were detected; suggesting the presence of at least 4 different species of pathogenic leptospires in the country (L. borgpetersenii; L. interrogans; L. kirschneri; and L. noguchii).

Leptospirosis in cats: Current literature review to guide diagnosis and management.

GLOBAL IMPORTANCE: Leptospirosis is the most widespread zoonosis worldwide. Mammals (eg, rats, horses, cows, pigs, dogs, cats and aquatic species, such as sea lions and northern elephant seals) can all be infected by leptospires. Infection in animals occurs through contact with urine or water contaminated with the bacteria. In people, the disease is acquired mainly from animal sources or through recreational activities in contaminated water. PRACTICAL RELEVANCE: Literature on the clinical presentation of leptospirosis in cats is scarce, although it has been demonstrated that cats are susceptible to infection and are capable of developing antibodies. The prevalence of antileptospiral antibodies in cats varies from 4% to 33.3% depending on the geographical location. Urinary shedding of leptospires in naturally infected cats has been reported, with a prevalence of up to 68%. Infection in cats has been associated with the consumption of infected prey, especially rodents. Thus, outdoor cats have a higher risk of becoming infected. CLINICAL CHALLENGES: Clinical presentation of this disease in cats is rare and it is not known what role cats have in the transmission of leptospirosis. Ongoing work is needed to characterise feline leptospirosis. AUDIENCE: This review is aimed at all veterinarians, both general practitioners who deal with cats on a daily basis in private practice, as well as feline practitioners, since both groups face the challenge of diagnosing and treating infectious and zoonotic diseases. EVIDENCE BASE: The current literature on leptospirosis in cats is reviewed. To date, few case reports have been published in the field, and information has mostly been extrapolated from infections in people and dogs. This review is expected to serve as a guide for the diagnosis and management of the disease in cats.

Identification of Host Cell Factors Associated with Astrovirus Replication in Caco-2 Cells.

UNLABELLED: Astroviruses are small, nonenveloped viruses with a single-stranded positive-sense RNA genome causing acute gastroenteritis in children and immunocompromised patients. Since positive-sense RNA viruses have frequently been found to replicate in association with membranous structures, in this work we characterized the replication of the human astrovirus serotype 8 strain Yuc8 in Caco-2 cells, using density gradient centrifugation and free-flow zonal electrophoresis (FFZE) to fractionate cellular membranes. Structural and nonstructural viral proteins, positive- and negative-sense viral RNA, and infectious virus particles were found to be associated with a distinct population of membranes separated by FFZE. The cellular proteins associated with this membrane population in infected and mock-infected cells were identified by tandem mass spectrometry. The results indicated that membranes derived from multiple cell organelles were present in the population. Gene ontology and protein-protein interaction network analysis showed that groups of proteins with roles in fatty acid synthesis and ATP biosynthesis were highly enriched in the fractions of this population in infected cells. Based on this information, we investigated by RNA interference the role that some of the identified proteins might have in the replication cycle of the virus. Silencing of the expression of genes involved in cholesterol (DHCR7, CYP51A1) and fatty acid (FASN) synthesis, phosphatidylinositol (PI4KIIIß) and inositol phosphate (ITPR3) metabolism, and RNA helicase activity (DDX23) significantly decreased the amounts of Yuc8 genomic and antigenomic RNA, synthesis of the structural protein VP90, and virus yield. These results strongly suggest that astrovirus RNA replication and particle assembly take place in association with modified membranes potentially derived from multiple cell organelles. IMPORTANCE: Astroviruses are common etiological agents of acute gastroenteritis in children and immunocompromised patients. More recently, they have been associated with neurological diseases in mammals, including humans, and are also responsible for different pathologies in birds. In this work, we provide evidence that astrovirus RNA replication and virus assembly occur in contact with cell membranes potentially derived from multiple cell organelles and show that membrane-associated cellular proteins involved in lipid metabolism are required for efficient viral replication. Our findings provide information to enhance our knowledge of astrovirus biology and provide information that might be useful for the development of therapeutic interventions to prevent virus replication.

Multiple-stressor interactions influence embryo development rate in the American horseshoe crab, Limulus polyphemus.

Fertilized eggs of the American horseshoe crab, Limulus polyphemus, are buried in shallow nests above the high tide line, where they are exposed to variations in abiotic conditions during early development. Using a multiple-stressors approach, we examined whether the rate of embryonic development is affected by exposure to combinations of three factors: temperature (25, 30 and 35°C), salinity (5, 15 and 34 ppt) and ambient O2 (5%, 13% and 21% O2). Newly fertilized eggs were incubated under 27 fully factorial stressor combinations for 14 days, then allowed to recover in control conditions (30°C, 34 ppt, 21% O2) for an additional 14 days. Growth rate was measured every 2 days throughout the experiment (N=1289). We found that the effect of isolated stressors (high temperature, low salinity or low O2) reduced developmental success by up to 72% (low salinity), and that stressor combinations showed stronger effects and evidence of complex interactions. For example, low O2 had little effect individually but was lethal in combination with high temperature, and low temperature in isolation slightly decreased the rate of development but reduced the negative effects of low salinity and low O2. Development was delayed under exposure to low O2 but resumed upon return to control conditions after a 10 day lag. These data demonstrate that complex, synergistic interactions among abiotic stressors can substantially alter the development of a coastal invertebrate in ways that may not be predicted from the effects of the stressors in isolation.

Inhibition of rotavirus infection in cultured cells by N-acetyl-cysteine, PPARγ agonists and NSAIDs.

Although the current rotavirus vaccines have shown good tolerance and significant efficacy, it would be useful to develop alternative or complementary strategies aimed at preventing or treating acute diarrhoeal disease caused by this viral agent. A variety of antiviral strategies other than vaccines have been assayed for rotavirus infection management. The recently demonstrated sensitivity of rotavirus infectivity to thiol/disulfide reagents prompted assays for screening drugs that potentially affect cellular redox reactions. MA104 or Caco-2 cells were inoculated with the rotavirus strains RRV, Wa, Wi or M69 and then incubated with different concentrations of drugs belonging to a selected group of 60 drugs that are currently used in humans for purposes other than rotavirus infection treatment. Eighteen of these drugs were able to inhibit rotavirus infectivity to different extents. A more systematic evaluation was performed with drugs that could be used in children such as N-acetylcysteine and ascorbic acid, in addition to ibuprofen, pioglitazone and rosiglitazone, all of which affecting cellular pathways potentially needed by the rotavirus infection process. Evidence is provided here that rotavirus infectivity is significantly inhibited by NAC in different cell-culture systems. These findings suggest that NAC has the potential to be used as a therapeutic tool for treatment and prevention of rotavirus disease in children.

Bone resorptive activity of osteoclast-like cells generated in vitro by PEG-induced macrophage fusion.

Normal bone remodeling is maintained by a balance between osteoclast and osteoblast activity, whereas defects in osteoclast activity affecting such balance result in metabolic bone disease. Macrophage-macrophage fusion leading to multinucleated osteoclasts being formed is still not well understood. Here we present PEG-induced fusion of macrophages from both U937/A and J774 cell lines and the induced differentiation and activation of osteoclast-like cells according to the expression of osteoclast markers such as tartrate resistant acid phosphatase (TRAP) and bone resorptive activity. PEG-induced macrophage fusion, during the non-confluent stage, significantly increased the osteoclastogenic activity of macrophages from cell lines compared to that of spontaneous cell fusion in the absence of PEG (polyethylene glycol). The results shown in this work provide evidence that cell fusion per se induces osteoclast-like activity. PEG-fused macrophage differential response to pretreatment with osteoclastogenic factors was also examined in terms of its ability to form TRAP positive multinucleated cells (TPMNC) and its resorptive activity on bovine cortical bone slices. Our work has also led to a relatively simple method regarding those previously reported involving cell co-cultures. Multinucleated osteoclast-like cells obtained by PEG-induced fusion of macrophages from cell lines could represent a suitable system for conducting biochemical studies related to basic macrophage fusion mechanisms, bone-resorption activity and the experimental search for bone disease therapeutic alternatives.

Bone resorptive activity of osteoclast-like cells generated in vitro by PEG-induced macrophage fusion

Normal bone remodeling is maintained by a balance between osteoclast and osteoblast activity, whereas defects in osteoclast activity affecting such balance result in metabolic bone disease. Macrophage-macrophage fusion leading to multinucleated osteoclasts being formed is still not well understood. Here we present PEG-induced fusion of macrophages from both U937/A and J774 cell lines and the induced differentiation and activation of osteoclast-like cells according to the expression of osteoclast markers such as tartrate resistant acid phosphatase (TRAP) and bone resorptive activity. PEG-induced macrophage fusion, during the non-confuent stage, signifcantly increased the osteoclastogenic activity of macrophages from cell lines compared to that of spontaneous cell fusion in the absence of PEG (polyethylene glycol). The results shown in this work provide evidence that cell fusion per se induces osteoclast-like activity. PEG-fused macrophage differential response to pretreatment with osteoclastogenic factors was also examined in terms of its ability to form TRAP positive multinucleated cells (TPMNC) and its resorptive activity on bovine cortical bone slices. Our work has also led to a relatively simple method regarding those previously reported involving cell co-cultures. Multinucleated osteoclast-like cells obtained by PEG-induced fusion of macrophages from cell lines could represent a suitable system for conducting biochemical studies related to basic macrophage fusion mechanisms, bone-resorption activity and the experimental search for bone disease therapeutic alternatives.

Voluntary ethanol consumption in 22 inbred mouse strains.

Inbred strains are genetically stable across time and laboratories, allowing scientists to accumulate a record of phenotypes, including physiological characteristics and behaviors. To date, the C57/C58 family of inbred mouse strains has been identified as having the highest innate ethanol consumption, but some lineages have rarely or never been surveyed. Thus, the purpose of the present experiment was to measure ethanol preference and intake in 22 inbred mouse strains, some of which have never been tested for ethanol consumption. Male and female mice (A/J, BALB/cByJ, BTBR+T(tf/tf), BUB/BnJ, C57BL/6J, C57BLKS/J, C58/J, CZECH/Ei, DBA/2J, FVB/NJ, I/LnJ, LP/J, MA/MyJ, NOD/LtJ, NON/LtJ, NZB/B1NJ, NZW/LacJ, PERA/Ei, RIIIS/J, SEA/GnJ, SM/J, and 129S1/SvlmJ) were individually housed and given unlimited access in a two-bottle choice procedure to one bottle containing tap water and a second containing increasing concentrations of ethanol (3%, 6%, 10%), 0.2% saccharin, and then increasing concentrations of ethanol (3%, 6%, 10%) plus 0.2% saccharin. Mice were given access to each novel solution for a total of 4 days, with a bottle side change every other day. Consistent with previous studies, C57BL/6J (B6) mice consumed an ethanol dose of >10g/kg/day whereas DBA/2J (D2) mice consumed <2g/kg/day. No strain voluntarily consumed greater doses of ethanol than B6 mice. Although the C58 and C57BLKS strains showed high ethanol consumption levels that were comparable to B6 mice, the BUB and BTBR strains exhibited low ethanol intakes similar to D2 mice. The addition of 0.2% saccharin to the ethanol solutions significantly increased ethanol intake by most strains and altered the strain distribution pattern. Strong positive correlations (rs> or =0.83) were determined between consumption of the unsweetened versus sweetened ethanol solutions. Consumption of saccharin alone was significantly positively correlated with the sweetened ethanol solutions (rs=0.62-0.81), but the correlation with unsweetened ethanol solutions was considerably lower (rs=0.37-0.45). These results add new strains to the strain mean database that will facilitate the identification of genetic relationships between voluntary ethanol consumption, saccharin preference, and other phenotypes.

DNA microsatellite characterization of the jaguar (Panthera onca) in Colombia.

The Colombian jaguar population is thought to contain two different subspecies, Panthera onca centralis and Panthera onca onca. The genetic structure of this population was evaluated using 12 microsatellite loci (n = 62 samples). In addition, 22 jaguar DNA samples from Guatemala, Paraguay, Perú, Bolivia, Venezuela and Brazil were analyzed for these microsatellite loci (n = 84 samples). The results of this study indicate six primary themes. First, the levels of gene diversity were very high. Second, the majority of the loci analyzed showed an absence of Hardy-Weinberg equilibrium, probably due to the Wahlund effect (= population subdivision). Third, several microsatellite loci showed significant heterogeneity between the two supposed subspecies in the country. Nevertheless, gene flow was present between them, and heterogeneity was relatively low, although the assignment analyses showed good classification of the jaguars studied into their respective subspecies. Fourth, the long-term historical effective population sizes were calculated through a maximum likelihood procedure for single and multi-step mutation models. Fifth, seven out of twelve DNA microsatellites studied significantly deviated from a single-step mutation model. However, the overall mean multi-step mutation percentage for these 12 DNA microsatellites was only 6%. Therefore, 94% of mutations were uni-step. Sixth, no bottleneck events were detected in the Colombian jaguar population overall.

Malaria grave, pielonefritis, sepsis, reacción leucemoide, abscesos hepáticos. A propósito de un caso clínico / Serious Malaria, pyelonephritis, sepsis, leucemoide reaction, liver abscesses. With regard to a clinical case

Caso problema de una paciente joven procedente de una zona endémica de malaria y una zona emergente de bartonellosis, que inicia un cuadro agudo de fiebre, ictericia y gran compromiso del estado general que la llevo al estado de shock séptico y por lo que fue atendida en este hospital. Durante su ingreso se plantearon patologías y diferentes entidades patológicas y que por prueba terapéutica se llegó al diagnóstico de malaria grave por Plasmodium falciparum. Presentó durante su evolución una serie de complicaciones tales como abscesos hepáticos y anemia severa, quedando por dilucidar si podría corresponder a un caso de bartonellosis.

A procedure to produce high alcohol intake in mice.

RATIONALE: While prolonged access to ethanol (EtOH), or deprivations, or their combination have occasionally been shown to yield high levels of voluntary self-administration, in almost all cases, rodents do not self-administer alcohol to the degree that they will develop substantial, intoxicating blood alcohol levels and then continue to self-administer at these levels. OBJECTIVES: The purpose of the present series of experiments was to modify a fluid restriction procedure to demonstrate consistent, high EtOH consumption. METHODS: Male and female mice from an alcohol preferring inbred strain (C57BL/6J; B6) as well as from a genetically heterogeneous strain (WSC) were given varying periods of access to fluid, ranging from 90 min to 10 h per day, for 12-21 days. Every 3rd or 4th day, separate groups of mice were offered a 5, 7 or 10% EtOH solution for either 10 min or 30 min, followed by water for the remainder of the time. RESULTS: In all studies, stable high EtOH doses were consumed by both B6 and WSC mice across the EtOH sessions, exceeding 2 g/kg in a 30-min session. Mean blood EtOH concentration exceeded 1 mg/ml (i.e. 100 mg%), with values in individual animals ranging from 0.6 mg/ml to 3.4 mg/ml. Notably, mice receiving 10 h of fluid/day continued to consume 2 g/kg doses of EtOH. While this procedure did not produce subsequent preference for EtOH in WSC mice, consumption remained high in some animals. CONCLUSIONS: These data indicate that scheduling fluid intake produces high, stable EtOH consumption and BEC in male and female B6 and WSC mice.

Coinjerto de nervio periferico y celulas neuronales embrionarias en corteza motora murina / Cografts of peripheral nerve and embrionic neuronal cells in murine motor cortex

El uso de injertos en el sistema nervioso central (SNC) ha sido una alternativa experimental muy usada en los últimos 15 años con el propósito de descifrar algunos de los enigmas concernientes a la falta de regeneración de las neuronas en el SNC. El remplazo de las células muertas o dañadas, y la aplicación de factores de crecimiento son hasta ahora las mejores estrategias para recuperar las funciones perdidas. Por medio de un modelo de lesión en la corteza motora murina (rata, cepa Sprague-Dawley), se evaluó el beneficio de un coinjerto de neuronas cerebelosas embrionarias de ratón (multipotentes e inmortalizadas C17-8) y de nervio periférico de rata, que actúa como reservorio del factor de crecimiento nervioso (Nerve Growth Factor, NGF) principalmente, con respecto a los injertos individuales de los mismos. Se incluyeron las variables peso y sexo para determinar si el modelo de lesión se puede aplicar a un amplio espectro experimental. Se encontró que no existe una covarianza del peso y del sexo respecto al desempeño funcional motor, comprobando así que el modelo de lesión es adecuado para un amplio espectro experimental. El análisis estadístico de los datos de la evaluación funcional motora reveló diferencias significativas entre los grupos que involucraron injerto (ciático, neuronas y coinjerto) y el grupo control de lesión, pero entre los grupos con injerto no existen diferencias significativas, por lo tanto son muy similares entre sí; así como tampoco existen diferencias en el desempeño funcional motor entre los tiempos de evaluación para todos los grupos. De esta forma se concluye que todos los tratamientos conllevan a una recuperación funcional motora con el tiempo, y que los injertos que contienen neuronas muestran una recuperación mayor en un menor tiempo...