ABSTRACT
AIMS: The goal of this study was to identify mediators in peri-lymphatic adipose tissue (PLAT) that are altered in obese versus lean Zucker rats, with focus on potential sex differences MAIN METHODS: Mesenteric PLAT was analyzed with protein and lncRNA arrays. Additional RT-PCR confirmation was performed with epididymal/ovarian fat. KEY FINDINGS: MCP-1, TCK-1, Galectin-1, Galectin-3, and neuropilin-1 were elevated in PLAT from obese rats of both sexes. However, 11 additional proteins were elevated only in obese males while 24 different proteins were elevated in obese females. Profiling of lncRNAs revealed lean males have elevated levels of NEAT1, MALAT1 and GAS5 compared to lean females. NEAT1, MALAT1, and GAS5 were significantly reduced with obesity in males but not in females. Another lncRNA, HOTAIR, was higher in lean females compared to males, and its levels in females were reduced with obesity. Obese rats of both sexes had similar histologic findings of mesenteric macrophage crown-like structures and hepatocyte fat accumulation. SIGNIFICANCE: While obese male and female Zucker rats both have increased inflammation, they have distinct signals. Future studies of the proteome and lncRNA landscape of obese males vs. females in various animal models and in human subjects are warranted to better guide development of therapeutics for obesity-induced inflammation.
Subject(s)
RNA, Long Noncoding , Female , Male , Rats , Humans , Animals , RNA, Long Noncoding/genetics , Rats, Zucker , Obesity/genetics , Obesity/metabolism , Adipose Tissue/metabolism , Inflammation/genetics , Inflammation/metabolism , Inflammation MediatorsABSTRACT
BACKGROUND: Goreisan is a traditional herbal formulation with diuretic properties tested as a clinical therapeutic to alleviate lymphedema in Japan. The present study aimed to determine how Goreisan and its five different components affect lymphatic pump function. METHODS: Mesenteric collecting lymphatics were isolated from anesthetized Sprague-Dawley rats and mounted on resistance-matched glass micropipettes in a 37°C physiological salt solution bath for studies. Diameter was continuously measured to obtain the following lymphatic pump parameters: contraction frequency (CF), end diastolic diameter (EDD), and end systolic diameter (ESD), contraction amplitude (AMP), ejection fraction (EF), and fractional pump flow (FPF). Goreisan and each of its components (Cinnamomi Cortex, Atractylodis Rhizoma, Alismatis Rhizoma, Polyporus, and Poria) were applied to the bath at concentrations of 1-30 µg/mL. RESULTS: The results show that while Goreisan causes no significant changes to lymphatic pumping, Alismatis Rhizoma and Polyporus each significantly reduce CF and FPF. In addition, rats that received oral administration of Goreisan and Alismatis Rhizoma for 1 week had elevated expression of VEGFR-3 in their mesenteric collecting lymphatics. CONCLUSIONS: Collectively, the results suggest that some components of Goreisan have a direct, rapid impact on lymphatic pumping. These findings provide new insights but also raise new questions about the therapeutic potential of Goreisan in patients with secondary lymphedema.
Subject(s)
Lymphatic Vessels , Lymphedema , Rats , Animals , Rats, Sprague-Dawley , Lymphatic SystemABSTRACT
Introducción y objetivo: Las lesiones de la extremidad inferior son una entidad frecuente y en ocasiones requieren tratamientos reconstructivos avanzados por zona afecta. Siempre se ha cuestionado sobre el mejor tiempo quirúrgico para reconstruir dichas lesiones. El objetivo de este estudio es aportar un mejor conocimiento sobre el tiempo recomendado para reconstrucción así como sobre la funcionalidad de la extremidad dependiendo de esa variable, análisis que extraemos del tratamiento y estudio de diversos casos tratados por los especialistas del Centro Médico Lic. Adolfo López Mateos en Toluca, México.Material y método. Estudio retrospectivo de casos abarcando distintas técnicas de análisis: observacional, estadística descriptiva para el análisis de datos y seguimiento de casos con lesión de pierna y pie con necesidad de manejo quirúrgico, revisando expedientes entre marzo de 2017 y febrero de 2020. Incluimos 29 expedientes en un estudio dividido en 4 grupos de reconstrucción: de 0 a 3 días; de 3 a 21 días; de 22 a 90 días; y más de 90 días. Resultados: El mecanismo de lesión más frecuente fue accidente por motocicleta y quemaduras en el 27.59% de los casos, seguido de atropello en el 17.24%. El tercio más afectado fue el inferior con un 37.93%. El tipo de colgajo más frecuentemente utilizado fue el sural reverso, con un 31.03%. Se reoperó el 13.70% de los pacientes y la principal complicación fue la necrosis total del colgajo en un 10.34%. Conclusiones: Encontramos el mayor número de complicaciones en el tercer grupo, en el que la reconstrucción se hizo entre los 22 y los 90 días, con mayor pérdida de los colgajos así como menor funcionalidad de la extremidad. De esto podemos deducir que el tiempo óptimo de reconstrucción de las lesiones de la extremidad inferior estaría dentro de los primeros 21 días. Así mismo, que es importante rehabilitar de forma oportuna para generar menores secuelas. (AU)
Background and objective: Lower extremity injures are a frequent entity and sometimes required advanced reconstructive treatments for each affected area. There has always been a question about when would be the best surgical time to perform reconstructions of these injuries. For this reason, the main objective of this study is to provide a better understanding of the time of reconstruction of the lower limb as well as the functionality, from cases analyzed at the Medical Center Lic. Adolfo López Mateos in Toluca, México. Methods: Retrospective case study combining different methods: observational, descriptive statistics for data analysis and follow-up of cases with leg and foot injuries requiring surgical management, reviewing files between March 2017 and February 2020. We included 29 cases divided into 4 recons- truction groups: from 0 to 3 days; from 3 to 21 days; from 22 to 90 days; and more than 90 days. Results: The most frequent injury mechanism was motorcycle accident and burns in 27.59%, followed by run over in 17.24%. The most affected leg third was the lower one in 37.93%. The most frequently used type of flap was sural reverse in 31.03%. The 13.70% of the patients underwent reoperation and the main complication was total necrosis of the flap in 10.34%. Conclusions: The highest number of complications were found in the third group with a reconstruction time of 22 to 90 days. The greatest flap losses occurred in this group as well as less functionality of the limb. From this we can deduce that an optimal reconstruction time for lower extremity injuries is within the first 21 days. Likewise, we can conclude that it is important to carry out rehabilitation in a timely manner to generate fewer sequelae. (AU)
Subject(s)
Humans , Adolescent , Young Adult , Adult , Middle Aged , Lower Extremity , Post Disaster Reconstruction , Free Tissue Flaps , Aftercare , Retrospective Studies , Data Analysis , AccidentsABSTRACT
BACKGROUND: Dengue fever is a major public health problem in Colombia. A fever surveillance study was conducted for evaluation of the clinical, epidemiological, and molecular patterns of dengue, prior to Chikungunya and Zika epidemics. METHODS: In November 2011-February 2014, a passive facility-based surveillance was implemented in Santa Cruz Hospital, Medellin, and enrolled eligible febrile patients between 1 and 65 years-of-age. Acute and convalescent blood samples were collected 10-21 days apart and tested for dengue using IgM/IgG ELISA. RNA was extracted for serotyping using RT-PCR on acute samples and genotyping was performed by sequencing. RESULTS: Among 537 febrile patients enrolled during the study period, 29% (n = 155) were identified to be dengue-positive. Only 7% of dengue cases were hospitalized, but dengue-positive patients were 2.6 times more likely to be hospitalized, compared to non-dengue cases, based on a logistic regression. From those tested with RT-PCR (n = 173), 17 were dengue-confirmed based on PCR and/or virus isolation showing mostly DENV-3 (n = 9) and DENV-4 (n = 7) with 1 DENV-1. Genotyping results showed that: DENV-1 isolate belongs to the genotype V or American/African genotype; DENV-3 isolates belong to genotype III; and DENV-4 isolates belong to the II genotype and specifically to the IIb sub-genotype or linage. CONCLUSIONS: Our surveillance documented considerable dengue burden in Santa Cruz comuna during non-epidemic years, and genetic diversity of circulating DENV isolates, captured prior to Chikungunya epidemic in 2014 and Zika epidemic in 2015. Our study findings underscore the need for continued surveillance and monitoring of dengue and other arboviruses and serve as epidemiological and molecular evidence base for future studies to assess changes in DENV transmission in Medellin, given emerging and re-emerging arboviral diseases in the region.
Subject(s)
Dengue Virus/genetics , Dengue Virus/immunology , Dengue/epidemiology , Fever/epidemiology , Genetic Variation , Adolescent , Adult , Aged , Child , Child, Preschool , Colombia/epidemiology , Dengue/virology , Dengue Virus/isolation & purification , Endemic Diseases , Enzyme-Linked Immunosorbent Assay , Female , Fever/virology , Genotype , Humans , Incidence , Infant , Male , Middle Aged , Multiplex Polymerase Chain Reaction , Phylogeny , Reverse Transcriptase Polymerase Chain Reaction , Young AdultABSTRACT
Ultrasound has been used since the 1950s as a useful tool for the screening of several pregnancy abnormalities. The National Institute for Excellence in Health and Care (NICE) guidelines for prenatal control recommend its routine use between 12 and 20 weeks of gestational age, given that during the first trimester, a series of very frequent markers that determine a high risk of fetal anomalies can be evaluated. Among these markers, the most frequently studied are: increased nuchal translucency, the absence of nasal bones, increased tricuspid regurgitation, and altered flow in the venous duct. There is also a new ultrasound technique consisting of the evaluation of the retronasal triangle view, which captures the coronal plane of the face in which the primary palate and the frontal process of the maxillary are simultaneously visualized, presenting high sensitivity and specificity for malformations such as oropalatine clefts, malformations of the nasal bones, and micrognathia. The purpose of this article is to make a comprehensive review of first trimester sonographic diagnosis of orofacial defects.
Subject(s)
Nasal Bone , Ultrasonography, Prenatal , Female , Gestational Age , Humans , Nasal Bone/diagnostic imaging , Nuchal Translucency Measurement , Pregnancy , Pregnancy Trimester, FirstABSTRACT
In the current study, the potential contributions of ryanodine receptors (RyRs) to intrinsic pumping and responsiveness to substance P (SP) were investigated in isolated rat mesenteric collecting lymphatic vessels. Responses to SP were characterized in lymphatic vessels in the absence or presence of pretreatment with nifedipine to block L-type Ca2+ channels, caffeine to block normal release and uptake of Ca2+ from the sarcoplasmic reticulum, ryanodine to block all RyR isoforms, or dantrolene to more selectively block RyR1 and RyR3. RyR expression and localization in lymphatics was also assessed by quantitative PCR and immunofluorescence confocal microscopy. The results show that SP normally elicits a significant increase in contraction frequency and a decrease in end-diastolic diameter. In the presence of nifedipine, phasic contractions stop, yet subsequent SP treatment still elicits a strong tonic contraction. Caffeine treatment gradually relaxes lymphatics, causing a loss of phasic contractions, and prevents subsequent SP-induced tonic contraction. Ryanodine also gradually diminishes phasic contractions but without causing vessel relaxation and significantly inhibits the SP-induced tonic contraction. Dantrolene treatment did not significantly impair lymphatic contractions nor the response to SP. The mRNA for all RyR isoforms is detectable in isolated lymphatics. RyR2 and RyR3 proteins are found predominantly in the collecting lymphatic smooth muscle layer. Collectively, the data suggest that SP-induced tonic contraction requires both extracellular Ca2+ plus Ca2+ release from internal stores and that RyRs play a role in the normal contractions and responsiveness to SP of rat mesenteric collecting lymphatics.NEW & NOTEWORTHY The mechanisms that govern contractions of lymphatic vessels remain unclear. Tonic contraction of lymphatic vessels caused by substance P was blocked by caffeine, which prevents normal uptake and release of Ca2+ from internal stores, but not nifedipine, which blocks L-type channel-mediated Ca2+ entry. Ryanodine, which also disrupts normal sarcoplasmic reticulum Ca2+ release and reuptake, significantly inhibited substance P-induced tonic contraction. Ryanodine receptors 2 and 3 were detected within the smooth muscle layer of collecting lymphatic vessels.
Subject(s)
Calcium Signaling , Lymphatic Vessels/metabolism , Muscle Contraction , Muscle, Smooth/metabolism , Ryanodine Receptor Calcium Release Channel/metabolism , Animals , Caffeine/pharmacology , Calcium Signaling/drug effects , Lymphatic Vessels/drug effects , Male , Mesentery , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Rats, Sprague-Dawley , Ryanodine/pharmacology , Ryanodine Receptor Calcium Release Channel/drug effects , Ryanodine Receptor Calcium Release Channel/genetics , Sarcoplasmic Reticulum/metabolism , Substance P/pharmacologyABSTRACT
Dengue virus (DENV) is a flavivirus responsible for the most common and burdensome arthropod-borne viral disease of humans[1]. DENV evolution has been extensively studied on broad geographic and time scales, using sequences from a single gene[2,3]. It is believed that DENV evolution in humans is dominated primarily by purifying selection due to the constraint of maintaining fitness in both humans and mosquitoes[4,5]. Few studies have explored DENV evolutionary dynamics using whole genome sequences, nor have they explored changes in viral diversity that occur during intra-epidemic periods. We used deep sequencing of the viral coding region to characterize DENV-1 evolution in a Colombian population sampled during two high-prevalence dengue seasons in which serotype dominance shifted. Our data demonstrate patterns of strain extinction and replacement within DENV-1 as its prevalence waned and DENV-3 became established. A comparison of whole-genome versus single-gene-based phylogenetic analyses highlights an important difference in evolutionary patterns. We report a trend of higher nonsynonymous to synonymous diversity ratios among non-structural (NS) genes, and statistically significantly higher values among these ratios in the NS1 gene after DENV-1 strain replacement. These results suggest that positive selection could be driving DENV evolution within individual communities. Signals of positive selection coming from distinct samples may be drowned out when combining multiple regions with differing patterns of endemic transmission as commonly done by large-scale geo-temporal assessments. Here, we frame our findings within a small, local transmission history which aids significance. Moreover, these data suggest that the NS1 gene, rather than the E gene, may be a target of positive selection, although not mutually exclusive, and potentially useful sentinel of adaptive changes at the population level.
Subject(s)
Dengue Virus/genetics , Dengue/virology , Endemic Diseases , Evolution, Molecular , Viral Nonstructural Proteins/genetics , Adolescent , Adult , Aged , Child , Child, Preschool , Colombia/epidemiology , Dengue/epidemiology , Dengue/transmission , Female , Genetic Variation , Genome, Viral , Humans , Male , Middle Aged , Phylogeny , Prevalence , RNA, Viral/isolation & purification , Selection, Genetic , Serogroup , Viral Envelope Proteins/genetics , Whole Genome Sequencing , Young AdultABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Piper auritum Kunth is employed as an aphrodisiac in the traditional medicine, but corroborative evidence for such effect is scarce. AIM OF THE STUDY: The pro-sexual effect of an aqueous extract of P. auritum and its possible mechanisms were analyzed in two paradigms of male sexual function. MATERIAL AND METHODS: Effects of an aqueous extract of P. auritum (PA, single administration) were investigated in the fictive ejaculation, and copulatory behavior paradigms in sexually sluggish male rats. WAY 100635 (antagonist of 5-HT1A receptors), atosiban (antagonist of oxytocinergic receptors), L-NAME (inhibitor of the nitric oxide synthase) and baclofen (antagonist of GABAB receptors) were used as pre-treatments in order to investigate the role of different neurotransmitter systems in PA actions. Chemical profile of PA was determined by Gases Chromatography and Ultra Performance Chromatography-Electrospray Ionization-Masses Spectrometry (UPLC-ESI-MS). RESULTS: In males with retarded ejaculation, PA stimulated ejaculatory behavior and recovered electromyographic activity of pelvic musculature participating in seminal emission and ejaculation. All pre-treatments blocked stimulating effects of PA on the fictive ejaculation; additionally WAY 100635 interfered with PA actions on ejaculatory behavior. Safrol, apigenin dimethylether, myristicin, vaccihein A, sakuranin and sakuranetin flavonoids, were main constituents of PA, with possible participation in its pro-sexual effects. CONCLUSIONS: Pro-sexual effects of P. auritum elicited at level of ejaculation were mediated by several neurotransmitter systems, among which serotonin and its 5-HT1A receptors play an important role. Present findings support P. auritum reputation as an aphrodisiac, with potential use in delayed ejaculation disorder.
Subject(s)
Aphrodisiacs/pharmacology , Piper , Plant Extracts/pharmacology , Sexual Behavior/drug effects , Animals , Aphrodisiacs/chemistry , Behavior, Animal/drug effects , Ejaculation/drug effects , Female , Male , Phytochemicals/analysis , Phytochemicals/pharmacology , Piper/chemistry , Piperazines/pharmacology , Plant Extracts/chemistry , Plant Leaves/chemistry , Pyridines/pharmacology , Rats, Wistar , Receptor, Serotonin, 5-HT1A/physiology , Serotonin 5-HT1 Receptor Antagonists/pharmacologyABSTRACT
Excessive microvascular permeability is a serious complication following hemorrhagic shock and resuscitation (HSR). S1P has been shown to ameliorate microvascular leakage in a model of combined alcohol intoxication and HSR. In the current study, we tested the hypothesis that S1P reduces HSR-induced microvascular leakage by preserving endothelial cell junctional structure and the endothelial glycocalyx through the protection of mitochondrial function. We used an established in vivo rat model of conscious HSR and assessed microvascular leakage, endothelial glycocalyx integrity, and mitochondrial function by intravital microscopy. Junctional integrity in the mesenteric microcirculation was assessed by confocal microscopy. Cultured rat intestinal microvascular endothelial cells monolayers were used to test the ability of S1P to protect against glycocalyx shedding and endothelial barrier dysfunction caused by direct disruption of mitochondrial integrity due to inhibition of mitochondrial complex III. The results show that in vivo, S1P protects against HSR-induced hyperpermeability, preserves the expression of adherens junctional proteins, and protects against glycocalyx degradation. S1P treatment during HSR also protects against mitochondrial membrane depolarization. S1P also protects against mitochondrial dysfunction-induced endothelial barrier dysfunction and glycocalyx degradation by acting through mitochondrial complex III. Taken together, our data indicate that S1P protects against HSR-induced mitochondrial dysfunction in endothelial cells, which in turn improves the structure of the endothelial glycocalyx after HSR and allows for better junctional integrity to the prevention of excess microvascular permeability.
Subject(s)
Capillary Permeability/drug effects , Endothelium, Vascular , Lysophospholipids/pharmacology , Mitochondria , Resuscitation , Shock, Hemorrhagic , Sphingosine/analogs & derivatives , Adherens Junctions/metabolism , Adherens Junctions/pathology , Animals , Cell Line , Endothelial Cells/metabolism , Endothelial Cells/pathology , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Male , Membrane Potential, Mitochondrial/drug effects , Microvessels/metabolism , Microvessels/pathology , Mitochondria/metabolism , Mitochondria/pathology , Mitochondrial Membranes/metabolism , Mitochondrial Membranes/pathology , Rats , Rats, Sprague-Dawley , Shock, Hemorrhagic/drug therapy , Shock, Hemorrhagic/metabolism , Shock, Hemorrhagic/pathology , Sphingosine/pharmacologyABSTRACT
Objective: Chronically ill patients heal recalcitrant ulcerative wounds more slowly. Human adipose-derived stem cells (hADSCs) play an important role in tissue regeneration and exosomes secreted by hADSC contribute to their paracrine signaling. In addition to cytokines, lipids and growth factors, hADSC secrete mRNA, miRNA, and long noncoding (lnc) RNA into exosomes. In this study we examined the role of lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), an abundant lncRNA in exosomes from conditioned media (CM), on cell migration and ischemic wound healing. Approach: CM and isolated exosomes from hADSC were applied to human dermal fibroblast (HDF) in scratch assays and electric cell-substrate impedance sensing (ECIS) assays. CM was also applied to a rat model of ischemic wound healing and wound closure was followed. Results: CM stimulated cell migration of HDFs in vitro by 48%. CM stimulated the closure of ischemic wounds in a rat model 50% faster than unconditioned media. The depletion of MALAT1 in adipose-derived stem cell (ADSC) CM significantly reduced cell migration. Since MALAT1 is secreted into exosomes, a purified population of exosomes was applied to HDF where they enhanced cell migration in a similar manner to FGF-2 or basic fibroblast growth factor (bFGF) in ECIS wound healing assays. The uptake of exosomes by HDF was shown using dynasore, an inhibitor that blocks clathrin- and caveolin-dependent endocytosis. Depletion of MALAT1 in hADSC with antisense oligonucleotides resulted in exosomes without MALAT1. These exosomes had an effect similar to the unconditioned, control media in ECIS assays. Innovation: Exosomes contain lncRNA MALAT1 and other factors that have the potential to stimulate HDF cell migration and angiogenesis involved in wound healing without applying stem cells to wounds. Conclusion: Our results show the potential of using topically applied ADSC-derived exosomes containing MALAT1 for treating ischemic wounds. This allows for harnessing the power of stem cell paracrine signaling capabilities without applying the cells.
ABSTRACT
Dengue fever is an increasing health problem in tropical and subtropical regions. During 2010 in Medellin, the younger population presented a particularly high dengue incidence rate. This study estimated dengue virus (DENV) transmission in schoolchildren (aged 5-19 years) in Medellin from 2010 to 2012. A longitudinal serological survey (IgG) and spatial analysis were conducted to determine the distribution of DENV seroprevalence. A total of 4,385 schoolchildren participated for at least one year. Dengue seroprevalence significantly increased during the studied period (53.8% to 64.6%; p < 0.001). A significantly higher seroconversion rate was observed in 2010-2011 (16.8%) compared to 2011-2012 (7.8%). Multivariate regression analysis showed that the main factor associated with the seroprevalence was the aging. Furthermore, in 2010, patients with high socioeconomic status presented a lower risk. Predominant multitypic and DENV4 monotypic antibody responses were demonstrated. Geostatistical analysis evidenced a temporal clustering distribution of DENV seroprevalence in 2010. Population density and Ae. aegypti House Index were significantly correlated with the observed pattern. This study revealed high DENV transmission in schoolchildren determined as "sentinel population." High DENV risk was found in districts with combined poorly socioeconomic conditions and densest human and mosquito populations. These findings may allow to target population for effective prevention and vaccination campaigns.
ABSTRACT
Recently, it has been reported that a σ-receptor antagonist could reduce inflammation-induced edema. Lymphatic vessels play an essential role in removing excess interstitial fluid. We tested the hypothesis that activation of σ-receptors would reduce or weaken collecting lymphatic contractions. We used isolated, cannulated rat mesenteric collecting lymphatic vessels to study contractions in response to the σ-receptor agonist afobazole in the absence and presence of different σ-receptor antagonists. We used RT-PCR and Western blot analysis to investigate whether these vessels express the σ1-receptor and immunofluorescence confocal microscopy to examine localization of the σ1-receptor in the collecting lymphatic wall. Using N-nitro-l-arginine methyl ester (l-NAME) pretreatment before afobazole in isolated lymphatics, we tested the role of nitric oxide (NO) signaling. Finally, we used 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate fluorescence as an indicator to test whether afobazole increases NO release in cultured lymphatic endothelial cells. Our results show that afobazole (50-150 µM) elevated end-systolic diameter and generally reduced pump efficiency and that this response could be partially blocked by the σ1-receptor antagonists BD 1047 and BD 1063 but not by the σ2-receptor antagonist SM-21. σ1-Receptor mRNA and protein were detected in lysates from isolated rat mesenteric collecting lymphatics. Confocal images with anti-σ1-receptor antibody labeling suggested localization in the lymphatic endothelium. Blockade of NO synthases with l-NAME inhibited the effects of afobazole. Finally, afobazole elicited increases in NO production from cultured lymphatic endothelial cells. Our findings suggest that the σ1-receptor limits collecting lymphatic pumping through a NO-dependent mechanism.NEW & NOTEWORTHY Relatively little is known about the mechanisms that govern contractions of lymphatic vessels. σ1-Receptor activation has been shown to reduce the fractional pump flow of isolated rat mesenteric collecting lymphatics. The σ1-receptor was localized mainly in the endothelium, and blockade of nitric oxide synthase inhibited the effects of afobazole.
Subject(s)
Lymphatic Vessels/drug effects , Lymphatic Vessels/metabolism , Mesentery/drug effects , Mesentery/metabolism , Nitric Oxide/biosynthesis , Receptors, Opioid, delta/agonists , Animals , Benzimidazoles/pharmacology , Cells, Cultured , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Enzyme Inhibitors/pharmacology , Male , Morpholines/pharmacology , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , NG-Nitroarginine Methyl Ester/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Opioid, delta/antagonists & inhibitorsABSTRACT
BACKGROUND: Dengue is an important public health problem worldwide. A vaccine has recently been licensed in some countries of Latin America and Asia. Recommendations for dengue vaccine introduction include endemicity and a high serological prevalence of dengue in the territories considering its introduction. METHODS: A community-based survey was conducted to estimate dengue seroprevalence and age-specific seroconversion rates in a community in Medellin, Colombia, using a dengue serological test (IgG indirect ELISA). Residents were selected at random and were first screened for dengue infection; they were then followed over 2.5 years. RESULTS: A total of 3684 individuals aged between 1 and 65 years participated in at least one survey. The overall dengue seroprevalence was 61%, and only 3.3% of seropositive subjects self-reported a past history of dengue. Among dengue virus (DENV)-naïve subjects with more than two visits (n=1002), the overall seroconversion rate was 8.7% (95% confidence interval 7.3-10.4) per 1000 person-months, over the study period. Overall, the mean age of DENV prevalent subjects was significantly higher than the mean age of seroconverted subjects. Specifically, DENV seropositivity over 70% was observed in participants over 21 years old. Serotype-specific plaque-reduction neutralization tests (PRNT) revealed that all four dengue serotypes were circulating, with DENV4 being most prevalent. CONCLUSIONS: These laboratory-based findings could inform dengue vaccine decisions, as they provide age-specific seroprevalence and seroconversion data, evidencing permanent and ongoing dengue transmission in the study area. This study provides evidence for the existing rates of secondary and heterotypic responses, presenting a challenge that must be addressed adequately by the new vaccine candidates.
Subject(s)
Dengue Vaccines , Dengue Virus/immunology , Dengue/epidemiology , Seroconversion , Adolescent , Adult , Antibodies, Viral , Child , Child, Preschool , Colombia/epidemiology , Dengue/virology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Infant , Male , Middle Aged , Neutralization Tests , Prevalence , Seroepidemiologic Studies , Serogroup , Young AdultABSTRACT
During an active surveillance study in school children in Medellin, we assessed the performance of two diagnostic strategies for dengue virus. A total of 41 patients with suspected dengue acute infection were evaluated. Diagnostic strategies consisted of one combining Panbio(®) Dengue virus IgM and IgG Capture ELISAs (enzyme-linked immunosorbent assays) with reverse transcriptase polymerase chain reaction (RT-PCR) and another using a commercial rapid SD Bioline Dengue Duo (IgG/IgM + NS1 Ag) test. These two strategies were compared with the enzyme-linked immunospot microneutralization test (ELISPOT-MNT). The sensitivity and specificity were 53.9% and 80.0% for the combination of Panbio(®) ELISAs and RT-PCR tests, and 30.8% and 73.3% for the SD Bioline Duo test, respectively. ELISPOT-MNT detected 16.4% additional cases and revealed the presence of neutralizing antibodies in all the acute samples, evidencing that they were all secondary infections. In contrast, Panbio(®) and SD Dengue Duo rapid tests only classified 23.0% and 26.9% of the cases as secondary dengue infections, respectively. Cohen's kappa coefficient and McNemar's association tests demonstrated a significant disagreement between the two diagnostic strategies and ELISPOT-MNT. Overall, these results evidence the relatively poor performances of commercial assays for the diagnosis of acute and secondary dengue infections, compared with ELISPOT-MNT, and raise concern about the accuracy of these assays for the diagnostic of dengue in endemic areas.
Subject(s)
Antibodies, Viral/blood , Dengue Virus/isolation & purification , Dengue/diagnosis , Dengue/epidemiology , Epidemics , Acute Disease , Adolescent , Child , Colombia/epidemiology , Dengue/immunology , Dengue/virology , Dengue Virus/genetics , Dengue Virus/immunology , Enzyme-Linked Immunosorbent Assay/standards , Enzyme-Linked Immunosorbent Assay/statistics & numerical data , Enzyme-Linked Immunospot Assay/standards , Enzyme-Linked Immunospot Assay/statistics & numerical data , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Reverse Transcriptase Polymerase Chain Reaction/standards , Reverse Transcriptase Polymerase Chain Reaction/statistics & numerical data , Schools , Sensitivity and SpecificityABSTRACT
Resumen La mucormicosis es una infección causada por hongos del orden de los mucorales; las infecciones causadas por estos hongos generalmente se adquieren por vía respiratoria ya que las esporas de estos se encuentran en el ambiente. En pacientes inmunocomprometidos o diabéticos descompensados, estos microorganismos pueden causar cuadros fatales. Puede presentarse en varias localizaciones, en este caso se tratará la localización pulmonar. La fiebre, la hemoptisis y el infarto tisular son característicos de la mucormicosis pulmonar. Radiológicamente, se puede encontrar consolidación lobar, lesiones aisladas, enfermedad nodular y cavitación. Una vez realizado el diagnóstico de mucormicosis de cualquier localización, se deben identificar los factores predisponentes y corregirlos o atenuarlos. En esta ocasión se presenta el caso clínico de una paciente de 61 años de edad con diabetes mellitus tipo 2 (DM2) de 10 años de evolución que ingresa al servicio de urgencias de esta institución con descontrol glucémico de 520 mg/dL, acompañado de fiebre y con cuadro clínico de infección de vías respiratorias en tratamiento. Se realiza la presentación del caso, su comparación con la literatura disponible y las conclusiones a las que se llegaron.
Abstract Mucormycosis is an infection caused by organisms that belong to a group of fungi called Mucoromycotina in the order Mucorales; Infections caused by these microorganisms, are usually acquired through the respiratory route since the spores of fungi are found in the environment. These infections are more common among people with a weakened immune system or diabetic people, and they could be fatal. Mucormycosis can be found in several localizations but this case will focus specifically in the lung. The symptoms associated with it are fever, hemoptysis, and tissular infarct. Radiographically, lobar consolidation, isolate mass, nodular component and cavitation can be found. Once the diagnostics is made, in any location, its important to identify the risk factors, and try to correct or improve them. In this occasion, the we present the case of a 62-years-old female, with diabetes mellitus type 2 with and 10 years of evolution,. She arrives to the emergency room of this institution with uncontrolled blood glucose (520 mg / dL), accompanied by fever.and respiratory infection, and is treated by a multidisciplinary team (internal medicine, surgery and infectology). This is the presentation of the case, its comparison with the available literature and the conclusions of the author.
ABSTRACT
The propensity for chronic wounds in humans increases with ageing, disease conditions such as diabetes and impaired cardiovascular function, and unrelieved pressure due to immobility. Animal models have been developed that attempt to mimic these conditions for the purpose of furthering our understanding of the complexity of chronic wounds. The model described herein is a rat ischemic skin flap model that permits a prolonged reduction of blood flow resulting in wounds that become ischemic and resemble a chronic wound phenotype (reduced vascularization, increased inflammation and delayed wound closure). It consists of a bipedicled dorsal flap with 2 ischemic wounds placed centrally and 2 non-ischemic wounds lateral to the flap as controls. A novel addition to this ischemic skin flap model is the placement of a silicone sheet beneath the flap that functions as a barrier and a splint to prevent revascularization and reduce contraction as the wounds heal. Despite the debate of using rats for wound healing studies due to their quite distinct anatomic and physiologic differences compared to humans (i.e., the presence of a panniculus carnosus muscle, short life-span, increased number of hair follicles, and their ability to heal infected wounds) the modifications employed in this model make it a valuable alternative to previously developed ischemic skin flap models.
Subject(s)
Disease Models, Animal , Ischemia/physiopathology , Skin/blood supply , Wound Healing/physiology , Animals , Female , Male , Rats , Silicones , Surgical Flaps/blood supplyABSTRACT
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Subject(s)
Measles/complications , Measles/diagnosis , Epidemiological Monitoring/organization & administration , Epidemiological Monitoring/standards , Measles Vaccine/immunology , Measles Vaccine/therapeutic use , Measles/epidemiology , Measles/immunology , Measles/prevention & control , Public Health/methods , Public Health/statistics & numerical data , Public Health/trends , Measles virus/isolation & purificationABSTRACT
Alveolar rhabdomyosarcoma (ARMS) is a rare tumor in adults. Cytologic diagnosis of metastatic ARMS to the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been reported rarely in the literature. A 20-year-old male with a history of ARMS in the right maxillary sinus resected one year earlier and pancreatitis treated two months earlier, presented on routine follow-up. Abdominal positron electron tomography-CT scan revealed a mass in the pancreas and fluorodeoxyglucose uptake in the left paraaortic lymph node. Subsequent magnetic resonance imaging of the abdomen showed a 3.6 × 6.4 cm mass in the tail of the pancreas. EUS-FNA was performed using a 22-gauge needle. Cytologic criteria and immunohistochemistry in the smears were analyzed. A diagnosis consistent with metastatic ARMS was rendered. Subsequent FISH analysis of the case and histologic review of the primary tumor supported the final diagnosis. A diagnosis of metastatic ARMS to the pancreas can be made by EUS-FNA. FISH can be used as an ancillary technique in diagnosing the tumor.