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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An obesity syndrome was found in a number of mice infected as young adults with canine distemper virus, a morbillivirus antigenically related to measles. Body weights of obese animals 16 to 20 weeks after infection were comparable to those reported for genetically obese mice and for mice rendered obese by hypothalamic lesions. The total number of adipocytes in specific fat deposits was greater in obese animals than in their lean littermates. This hyperplasia was accompanied by moderate cell enlargement. Pancreatic islet tissue was also hypercellular in the obese mice. Brain tissue from the obese mice showed no overt pathology, and immunofluorescence staining for viral antigens was negative. There may be a selective, virus-induced disruption of critical brain catecholamine pathways.
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PMID:A virally induced obesity syndrome in mice. 703 78

Paramyxoviruses such as measles virus or canine distemper virus are etiological agents for acute and chronic encephalitis (measles inclusion body encephalitis, subacute sclerosing panencephalitis and chronic distemper encephalitis or old dog encephalitis). The mechanisms by which viral injury leads to neurological diseases have not yet been fully elucidated. We have developed an experimental model in mice in order to analyze the spatial and temporal distribution of canine distemper virus in the central nervous system. Cerebral target structures for viral replication were examined for the presence of viral material (proteins and mRNA) during the two stages of the biphasic disease. During the acute stage of infection all target areas could be identified by day 6 with a similar anatomical distribution in all the animals examined, which were either intracranially or intracerebroventricularly infected. Viral mRNA and proteins were selectively localized in certain brain structures such as the thalamus, hypothalamus, substantia nigra (pars compacta), locus ceruleus and raphe nuclei (dorsalis and centralis), and limbic system (hippocampus, septum, entorhinal and cingulate cortex, amygdala). The virus was apparently unable to replicate in cerebellum, striatum, a large part of cortex, or endothelial cells. During the subacute disease, viral material was no longer detectable except in a few structures such as hypothalamus up to 4-6 weeks after inoculation. After this time, all target structures were devoid of any labeling in spite of the occurrence of pathology (obesity, paralysis) during this viral quiescent phase. These results suggest that after the initial viral exposure, expression of viral genes in defined structures might disrupt central homeostasis and finally may lead to neurological or neuroendocrine diseases, even in the absence of the hallmarks of the virus.
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PMID:Brain structures selectively targeted by canine distemper virus in a mouse model infection. 836 Jul

It is currently well established that the nervous, endocrine and immune systems inter-communicate using biologically active soluble factors, synthesised and produced by these three systems themselves (e.g. immunomodulator effect of hormones, effect of substances secreted by immune cells on endocrine function.). In addition, these systems jointly express receptors for hormones, peptides, growth factors and cytokines. Immuno-neuroendocrine interactions therefore underlie physiological processes and their deregulation can result in various pathological states. By entering into complex relationships with the specialized and differentiated cells of these three systems viruses can alter inter-cellular communication and result in the appearance of pathological processes directly linked to these disturbances. In order to understand the role of viruses in the genesis of neuroimmunoendocrine pathologies, we have developed a cerebral infection model using canine distemper virus (CDV). In infected mice, this paramyxovirus, closely related to the human measles virus, induces early neurological pathologies (encephalitis) which are associated with active viral replication. Mice surviving the acute phase of infection exhibit motor deficits (paralysis and turning behaviour) or obesity during the viral persistence phase, despite the fact that the virus is no longer detectable. The obesity is characterised by hyperinsulinaemia, hyperleptinaemia and hyperplasia of the adipocytes, associated with decreased expression of the OB-Rb hypothalamic leptin receptor and modulated expression of hypothalamic monoamines and neuropeptides. These results support the viral "hit and run" theory, since the initial viral impact in the hypothalamus may be the origin of the changes in later immunoneuroendocrine communication. Thus, certain human neurodegenerative or neuroendocrine diseases may have a previous viral infection aetiology without it being possible to clearly identify the agent responsible.
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PMID:[Viruses and the neuroendocrine system: model of murine obesity induced by cerebral infection by canine distemper virus]. 1037 79

Obesity is a complex disease involving genetic components and environmental factors and probably associated with the dysregulation of central homeostasis normally maintained by the hypothalamic neuroendocrine/neurotransmitter network. We previously reported that canine distemper virus (CDV), which is closely related to human measles virus, can target hypothalamic nuclei, and lead to obesity syndrome in the late stages of infection. Here, using differential display PCR, we demonstrate specific down-regulation of melanin-concentrating hormone precursor mRNA (ppMCH) in infected-obese mice. Although ppMCH was down-regulated in all infected mice during the acute stage of infection, this was only seen during the late stage of infection in infected-obese mice. In addition, ppMCH mRNA and protein expression in the lateral hypothalamus was decreased in the absence of neuronal death. These results show the importance of ppMCH in the establishment and maintenance of obesity and the involvement of a virus as an environmental factor.
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PMID:Down regulation of melanin concentrating hormone in virally induced obesity. 1147 54

Neurotropic viruses are involved in pathologies of the central nervous system, triggering transient or irreversible disorders, such as neurological diseases or homeostasis imbalance. In experimental animals, viruses have been shown to cause obesity, a complex disease depending on multiple factors, including genetic susceptibility and environmental components. Using a mouse model of virally induced obesity following brain infection by the Canine Distemper Virus (CDV), a morbillivirus closely related to the human measles virus, we investigated the modulation of expression of several hypothalamic neuropeptides known to intervene in the regulation of body weight and energy expenditure, both during the acute and late stages of infection. During the acute stage, while viral replication occurs, we found a dramatic decrease of expressions of neuropeptides, in particular neuropeptide Y, melanin-concentrating hormone (MCH), hypocretin, vasopressin and tachykinins, the magnitude of which seemed to be linked to the viral burden and the individual susceptibility. The effect of the virus, however, varied with the hypothalamic nucleus and neuropeptide involved, suggesting that certain circuits were affected while others remained intact. During the late stage of infection, marked recovery to the initial hypothalamic levels of peptide expression was seen in a number of lean animals, suggesting recovery of homeostasis equilibrium. Interestingly, some neuropeptidergic systems remained disturbed in mice exhibiting obese phenotype, arguing for their involvement in triggering/maintaining obesity. Even though our data could not fully explain the viral-induced obesity, they may be helpful in understanding the molecular events associated with obesity and in investigating therapeutic alternatives.
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PMID:Specific alteration of the expression of selected hypothalamic neuropeptides during acute and late mouse brain infection using a morbillivirus: relevance to the late-onset obesity? 1535 27

An open controlled trial of 0.75 mg/Kg/day prednisolone was conducted at a stage when the patients had started falling several times in a day and stopped on their attaining a chair bound stage, thus minimising the total period of steroid therapy. Out of the 67 DMD patients enrolled in this study, 44 were put on prednisolone therapy and 23 served as controls. All patients were followed-up at two-monthly intervals for two years and thereafter they continued to take their respective medications till their chair-bound stage; then the drug was gradually withdrawn. In the treatment group 24 patients could not continue the trial because of adverse effects - 14 due to excessive obesity, 3 due to measles, 4 due to pulmonary tuberculosis, 2 due to recurrent throat and chest infection and 1 due to an unexplained high leukocyte count. Of the remaining 20 patients in the treatment group, steroid therapy was stopped in 5 patients as there was no improvement in power in six months. Fifteen patients in the treatment group and 19 patients in the control group could be followed regularly for 2 years and then up to chair-bound stage. Outcome parameters included fall frequency, peak expiratory flow rate, limb muscle power, ability to lift weights, time taken in getting up from squatting position, walking 9 metres and climbing 13 stairs. Maximum improvement was noted between 2 and 4 months while mild improvement in some parameters continued up to six months. All parameters remained stabilised for 1 year or so, after which there was slight deterioration. Deterioration at 2 years was, however, less than the natural course of events noted in control patients. Prednisolone treated patients and controls became chair bound at the mean age of 169 +/- 9 and 132 +/- 8 months respectively. Till the ideal stage of the disease and the type or dosage of starting steroid therapy is defined by specially designed studies, 0.75 mg/Kg/day prednisolone therapy may be started in DMD patients at the stage of frequent falls ( > 10 / day) on walking or increased get-up time ( > 10 s) as observed while testing Gowers' sign; this improves muscle power and timing of motor performance within 2-4 months of onset of therapy in about 75% of those who tolerate this therapy, with a possible gain of approximately 3 years in terms of independent walking.
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PMID:Prednisolone in Duchenne muscular dystrophy with imminent loss of ambulation. 1678 14

France has recently witnessed a nationwide outbreak of measles. Data on severe forms of measles in adults are lacking. We sought to describe the epidemiologic, clinical, treatment, and prognostic aspects of the disease in adult patients who required admission to an intensive care unit (ICU). We performed a retrospective analysis of a cohort of 36 adults admitted to a total of 64 ICUs throughout France for complications of measles from January 1, 2009, to December 31, 2011. All cases of measles were confirmed by serologic testing and/or reverse transcription polymerase chain reaction.The cohort consisted of 21 male and 15 female patients, with a median age of 29.2 years (25th-75th interquartile range [IQR], 27.2-34.2 yr) and a median Simplified Acute Physiology Score (SAPS II) of 13 (IQR, 9-18). Among the 26 patients whose measles vaccination status was documented, none had received 2 injections. One patient had developed measles during childhood. Underlying comorbid conditions included chronic respiratory disease in 9 patients, immunosuppression in 7 patients, and obesity in 3 patients, while measles affected 5 pregnant women.Respiratory complications induced by measles infection led to ICU admission in 32 cases, and measles-related neurologic complications led to ICU admission in 2 cases. Two patients were admitted due to concurrent respiratory and neurologic complications.Bacterial superinfection of measles-related airway infection was suspected in 28 patients and was documented in 8. Four cases of community-acquired pneumonia, 6 cases of ventilator-associated pneumonia, 1 case of tracheobronchitis, and 2 cases of sinusitis were microbiologically substantiated.Of 11 patients who required mechanical ventilation, 9 developed acute respiratory distress syndrome (ARDS). Among the patients with ARDS, extraalveolar air leak complications occurred in 4 cases. Five patients died, all of whom were severely immunocompromised.On follow-up, 1 patient had severe chronic respiratory failure related to lung fibrosis, and 2 patients had mild lower limb paraparesis along with bladder dysfunction, both of which were ascribable to measles-induced encephalitis and myelitis. Among the 5 pregnant patients, the course of measles infection was uneventful, albeit 1 patient underwent emergent cesarean delivery because of fetal growth restriction.Measles is a disease with protean and potentially deceptive clinical manifestations, especially in the immunocompromised patient. Measles-associated pneumonitis and its complications, and less commonly postinfectious encephalomyelitis, are the main source of morbidity and mortality. In contrast with the usually benign course of the disease in immunocompetent patients, measles occurring in immunocompromised patients gives rise to lethal complications including ARDS, with or without bacterial superinfection. Other patients potentially at high risk for severe measles are young adults and pregnant women. Measles pneumonitis may predispose to air leak disease in patients using mechanical ventilation. To date, vaccination remains the most potent tool to control measles infection.
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PMID:Severe Measles Infection: The Spectrum of Disease in 36 Critically Ill Adult Patients. 2398 57

2018 marks the 100-year anniversary of the 1918 influenza pandemic, which killed ~50 million people worldwide. The severity of this pandemic resulted from a complex interplay between viral, host, and societal factors. Here, we review the viral, genetic and immune factors that contributed to the severity of the 1918 pandemic and discuss the implications for modern pandemic preparedness. We address unresolved questions of why the 1918 influenza H1N1 virus was more virulent than other influenza pandemics and why some people survived the 1918 pandemic and others succumbed to the infection. While current studies suggest that viral factors such as haemagglutinin and polymerase gene segments most likely contributed to a potent, dysregulated pro-inflammatory cytokine storm in victims of the pandemic, a shift in case-fatality for the 1918 pandemic toward young adults was most likely associated with the host's immune status. Lack of pre-existing virus-specific and/or cross-reactive antibodies and cellular immunity in children and young adults likely contributed to the high attack rate and rapid spread of the 1918 H1N1 virus. In contrast, lower mortality rate in in the older (>30 years) adult population points toward the beneficial effects of pre-existing cross-reactive immunity. In addition to the role of humoral and cellular immunity, there is a growing body of evidence to suggest that individual genetic differences, especially involving single-nucleotide polymorphisms (SNPs), contribute to differences in the severity of influenza virus infections. Co-infections with bacterial pathogens, and possibly measles and malaria, co-morbidities, malnutrition or obesity are also known to affect the severity of influenza disease, and likely influenced 1918 H1N1 disease severity and outcomes. Additionally, we also discuss the new challenges, such as changing population demographics, antibiotic resistance and climate change, which we will face in the context of any future influenza virus pandemic. In the last decade there has been a dramatic increase in the number of severe influenza virus strains entering the human population from animal reservoirs (including highly pathogenic H7N9 and H5N1 viruses). An understanding of past influenza virus pandemics and the lessons that we have learnt from them has therefore never been more pertinent.
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PMID:Back to the Future: Lessons Learned From the 1918 Influenza Pandemic. 3034 11

Malnourishment, specifically overweight/obesity and undernourishment, affects more than 2.5 billion people worldwide, with the number affected ever-increasing. Concurrently, emerging viral diseases, particularly those that are mosquito-borne, have spread dramatically in the past several decades, culminating in outbreaks of several viruses worldwide. Both forms of malnourishment are known to lead to an aberrant immune response, which can worsen disease outcomes and reduce vaccination efficacy for viral pathogens such as influenza and measles. Given the increasing rates of malnutrition and spread of arthropod-borne viruses (arboviruses), there is an urgent need to understand the role of host nutrition on the infection, virulence, and transmission of these viruses. To address this gap in knowledge, we infected lean, obese, and undernourished mice with arthritogenic arboviruses from the genus Alphavirus and assessed morbidity, virus replication, transmission, and evolution. Obesity and undernourishment did not consistently influence virus replication in the blood of infected animals except for reductions in virus in obese mice late in infection. However, morbidity was increased in obese mice under all conditions. Using Mayaro virus (MAYV) as a model arthritogenic alphavirus, we determined that both obese and undernourished mice transmit virus less efficiently to mosquitoes than control (lean) mice. In addition, viral genetic diversity and replicative fitness were reduced in virus isolated from obese compared to lean controls. Taken together, nutrition appears to alter the course of alphavirus infection and should be considered as a critical environmental factor during outbreaks.
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PMID:Host nutritional status affects alphavirus virulence, transmission, and evolution. 3171 Jun 53

The aim of this serological survey was to assess the persistence of measles antibodies among health care workers (HCWs) at risk of incidental measles. A prospective study of measles-specific antibodies in serum samples obtained from a total of 2782 participants aged 19-89 years was conducted between May 2018 and December 2019. The seropositivity rate of 93.7% (95% CI: 92.4-94.9%) in fully vaccinated participants aged 19-48 years was significantly lower than that of 98.0% (95% CI: 96.5-99.0%) in participants naturally immunised before 54 years. A cohort of those born in 1971-1975, vaccinated predominantly with one dose, showed lower seropositivity persistence (86.6%) than those fully vaccinated with two doses or naturally immunised. Otherwise, seropositivity was not markedly influenced by sex, age, smoking status, overweight, obesity or concomitant disease. The presence of sufficient antibody levels in a high proportion of HCWs irrespective of the way they acquired immunity is a favourable finding for managing incidental measles; hence, in the presence of a risk of a measles outbreak, it would be possible to perform targeted vaccination of only at-risk HCWs with a history of incomplete vaccination or missing information about the way in which immunity is acquired.
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PMID:A Serosurvey Identifying Vulnerability to Measles in Health Care Workers. A Hospital-Based Prospective Seroprevalence Study. 3254 6


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