21 research outputs found
Dysregulated activation of immune-inflammatory responses contributes to vascular damage in atherosclerosis and hypertension
No full textAtherosclerosis and hypertension (HTN) are major contributors to the development and progression of cardiovascular disease (CVD). The underlying pathophysiology of atherosclerosis and HTN is similar in that both affect the structural and functional properties of the vasculature as a result of enhanced immune-inflammatory processes in the vascular wall. Vasoactive peptides such as angiotensin (Ang) II and endothelin (ET)-1 can contribute to vascular inflammatory responses and damage, and have been implicated in the progression of both atherosclerosis and HTN. We hypothesize that dysregulated activation of immune-inflammatory mechanisms by vasoactive peptides contributes to the progression of vascular damage in atherosclerosis and HTN.The objectives of this thesis were 1) to determine the role of ET-1-mediated vascular immune-inflammatory mechanisms in progression of hyperlipidemia-induced atherosclerosis and formation of abdominal aortic aneurysms (AAA), 2) to investigate the contribution of pro-inflammatory ET-1 signaling to small artery dysfunction in hyperlipidemia-induced atherosclerosis, and 3) to study the role of anti-inflammatory T regulatory lymphocytes on vascular immune-inflammatory responses in Ang II-induced HTN.The first study shows that endothelium-specific ET-1 overexpression in atherosclerotic apolipoprotein E knockout (Apoe-/-) mice fed a high fat diet exaggerates development of aortic atherosclerotic plaques and triggers formation of AAA. This is accompanied by increase in aortic immune-inflammatory responses, spleen pro-inflammatory monocytes, and expression of matrix metalloproteinase-2 in atherosclerotic plaques. This study also suggests that the suppressive capacity of T regulatory lymphocytes may be reduced during atherosclerosis progression.The second study shows that ET-1 overexpression in high fat diet-fed atherosclerotic Apoe-/- mice results in remodeling of endothelial signaling pathways and potassium channels mediating endothelium-dependent relaxation. Although this remodeling manifests as compensatory preservation of endothelial function, it may in fact represent loss of regulation of endothelium-dependent relaxation in resistance arteries.The third study demonstrates that absence of T regulatory lymphocytes exaggerates microvascular damage in Ang II-induced HTN. The findings of this study show that T regulatory lymphocytes exert vascular protection in part by controlling innate and adaptive immune responses.To conclude, chronic low-grade vascular inflammation in atherosclerosis and HTN involves vasoactive peptide-mediated dysregulation of pro-inflammatory and anti-inflammatory mechanisms in favor of the former. Targeting immune-inflammatory mechanisms may allow us to limit the progression of atherosclerosis and HTN, and therefore the development of CVD.L'athérosclérose et l'hypertension (HTN) sont les causes majeures du développement ainsi que l'aggravation des maladies cardio-vasculaires. Les causes de ses maladies sont similaires dans les deux cas, une altération de la structure et de la fonction des vaisseaux induites par une inflammation dans la paroi de ceux-ci. Les peptides vaso-actifs tels que l'angiotensine (Ang) II et l'endotheline (ET)-1 participent aux réponses inflammatoires et aux dommages que subissent les vaisseaux, et sont impliqués dans la progression de l'athérosclérose et de l'hypertension. Nous supposons que cette dysfonction inflammatoire par les peptides vaso-actifs contribue aux dommages vasculaires liés à l'athérosclérose et à l'hypertension.Les objectifs de cette thèse sont 1) de déterminer le rôle inflammatoire d’ET-1 dans les mécanismes de progression de l'hyperlipidémie induisant l'athérosclérose et dans la formation des anévrismes de l’aorte abdominale (AAA), 2) d’étudier la contribution pro-inflammatoire d’ET-1 dans la dysfonction endothéliale des artères de résistances dans l'athérosclérose induite par l’hyperlipidémie 3) d’évaluer le rôle des lymphocytes T régulateurs anti-inflammatoires sur les réponses immunitaires vasculaires T dépendantes dans HTN induite par l’Ang II.La première étude montre, dans un modèle murin de surexpression d’ET-1 endothélium-spécifique, sur des souris n’exprimant pas l’apolipoprotéine E (ApoE -/-) et nourris avec un régime riche en graisses, une exagération des plaques d'athérome aortique favorisant la formation des AAA. Ceci s’accompagne d'une augmentation de la réponse inflammatoire dans l'aorte, et d’une augmentation des monocytes pro-inflammatoires dans la rate. L’ensemble de ces mécanismes sont liés à la métalloprotéinase 2 dans les plaques d'athérome. Cette étude suggère également que la capacité suppressive des lymphocytes T régulateurs peut être réduite au cours de l'athérosclérose.La deuxième étude montre, dans le même modèle, une altération des voies de signalisation des canaux potassiques favorisant la relaxation endothélium. Cependant, elle se manifeste par un remodelage compensatoire afin de préserver la fonction endothéliale dans les artères de résistance.La troisième étude démontre que l'absence de lymphocytes T régulateurs exagère les lésions microvasculaires dans HTN induite par l’AngII. Les résultats de cette étude montrent que les lymphocytes T régulateurs exercent une protection vasculaire en contrôlant les réponses immunitaires innées et adaptatives.Pour conclure, l'inflammation vasculaire chronique à bas bruit, dans l'athérosclérose et HTN, le dérèglement est médié par les peptides vaso-actifs et leurs composantes pro-inflammatoires ce qui altère les mécanismes anti-inflammatoires protecteurs dans ces pathologies. Cibler les mécanismes immunitaires inflammatoires peut nous permettre de limiter la progression de l'athérosclérose et HTN, et donc le développement des maladies cardio-vasculaires
Crimean-Congo hemorrhagic fever outbreak in Chakwal, Pakistan
Get PDFCCHF, tick, livestock, diagnostics, геморрагическая лихорадка Крым-Конго, клещи, домашний скот, диагностика, клинические симптомы, летальный исходCrimean-Congo hemorrhagic fever (CCHF) is the most fatal viral disease with extensive geographical distribution. In Pakistan it is being reported with sporadic outbreaks in cattle rearing areas. The authors in this study presented a clinical case of CCHF in one of cattle rearing district Chakwal of Punjab rovince. The serums and plasma samples from suspected patients along with Hyalomma ticks from reported area were collected and diagnosed for CCHF antigen and IgG antibodies by two step sandwich enzyme-linked immunosorbent assay (ELISA) using Vector BEST Company, Crimean-CHF-antigen kit, Novosibirsk, Russia. Crimean-Congo hemorrhagic fever (CCHF) was suspected in three patients among which two patients died. The only survived patient was diagnosed for CCHF by detecting IgG. Out of 62 Hyalomma ticks collected from livestock of endemic area, 9.67% (6/62) were positive for the CCHF virus. This confirms the emergence of CCHF virus in new areas and the potential risk of its wide spread in different areas of Punjab, Pakistan.Геморрагическая лихорадка Крым-Конго (CCHF) является наиболее смертельным вирусным заболеванием с обширным географическим распространением. В Пакистане сообщается о спорадических вспышках в районах, где интенсивно выращивается крупный рогатый скот. Авторы данного исследования представили клинический случай CCHF в одном из районов, специализирующемся на разведении крупного рогатого скота - район Чаквал провинции Пенджаб. Сыворотки и образцы плазмы у подозреваемых пациентов вместе с клещами Hyalomma из сообщаемой области были собраны и диагностированы на антиген CCHF и IgG-антител с помощью двухступенчатого сэндвич-фермент-связанного иммуносорбентного анализа (ELISA) с использованием Vector BEST Company, набора крымских-CHF-антигенов, Новосибирск, Россия. Геморрагическая лихорадка Крым-Конго (CCHF) подозревалась у трех пациентов, из которых умерли два пациента. Единственный выживший пациент был диагностирован на CCHF по обнаружению IgG. Из 62 клещей Hyalomma, обнаруженных на крупном рогатом скоте эндемического района, 9,67% (6/62) дали положительный результат на наличие вируса CCHF. Это подтверждает появление вируса CCHF в новых областях и указывает на потенциальный риск его широкого распространения в разных районах Пенджаба, Пакистан
Distribution of Ixodid Tick Species and Associated Risk Factors in Temporal Zones of Khyber Pakhtunkhwa Province, Pakistan
No full textPesticide Efficiency of Environment-Friendly Transition Metal-Doped Magnetite Nanoparticles
No full textThis study explored the potential of Fe3O4, SnFe2O4, and CoFe2O4 nanoparticles as larvicidal and adulticidal agents against Aedes aegypti (A. aegypti) larvae and adults, which are vectors for various diseases. This research involved the synthesis of these nanoparticles using the coprecipitate method. The results indicate that CoFe2O4 nanoparticles are the most effective in both larvicidal and adulticidal activities, with complete mortality achieved after 96 h of exposure. SnFe2O4 nanoparticles also showed some larvicidal and adulticidal efficacy, although to a lesser extent than the CoFe2O4 nanoparticles. Fe3O4 nanoparticles exhibited minimal larvicidal and adulticidal effects at low concentrations but showed increased efficacy at higher concentrations. The study also revealed the superparamagnetic nature of these nanoparticles, making them potentially suitable for applications in aquatic environments, where A. aegypti larvae often thrive. Additionally, the nanoparticles induced observable damage to the gut structure of the mosquitoes and larvae, which could contribute to their mortality. Overall, this research suggests that CoFe2O4 nanoparticles, in particular, hold promise as environment-friendly and effective agents for controlling A. aegypti mosquitoes, which are responsible for the transmission of diseases such as dengue fever, Zika virus, and Chikungunya. Further studies and field trials are needed to validate their practical use in mosquito control programs
Prevalence of antibodies to Neospora caninum in the serum of camels (Camelus dromedarius) from central Punjab, Pakistan
No full textPrevalence of Toxoplasma gondii, Neospora caninum, and Sarcocystis Species DNA in the Heart and Breast Muscles of Rock Pigeons (Columbia livia)
No full textLittle is known about the prevalence of protozoan parasites in the muscles of rock pigeons (Columbia livia). The muscles from 54 (heart from 45 and breast from 54) rock pigeons were examined for DNA of Toxoplasma gondii, Neospora caninum, and Sarcocystis species using PCR. Twenty-four were female and 30 were males. The birds were part of flocks of pigeons housed at the tombs of saints in Lahore, Pakistan. Birds that died or were euthanized due to poor health were submitted for necropsy at the Department of Parasitology, University of Veterinary and Animal Sciences, Lahore, Pakistan, where DNA isolations and PCR were conducted. Nineteen (35.1%) of the birds were positive for T. gondii DNA. Seven males and 12 females were positive. Breast tissue was always infected in T. gondii positive birds, while the heart was infected in 13 (28.8%) of breast positive birds. Five (9.2%) of the pigeons, 2 males and 3 females, were positive for N. caninum. The distribution of N. caninum DNA was more variable in the muscles of pigeons than T. gondii and was found only in the heart of 1 (female), heart and breast muscle of 2 (male), and only the breast muscle of 2 birds (female). One of the 54 rock pigeons (female) was positive for both T. gondii (heart and breast) and N. caninum (heart only). Two of the positive Neospora caninum amplicons were sequenced and had 97% nucleotide identity with N. caninum isolates. Sarcocystis DNA was not found in any bird. The prevalence of T. gondii in rock pigeons and their predation by cats suggest that they may play an unrecognized role in maintaining environmental contamination with T. gondii oocysts by cats. Our study indicates that rock pigeons are intermediate hosts of N. caninum and this information will aid in understanding the epidemiology of N. caninum
Crimean–Congo Haemorrhagic Fever: Case study analysis of a sporadic outbreak from Chakwal, Pakistan
No full textContrasting population genetics of cattle-and buffalo-derived Theileria annulata causing tropical theileriosis
Get PDFThe present study was designed to improve understanding of Theileria annulata in sympatric water buffalo and cattle in the Punjab province of Pakistan. The prevalence of tropical theileriosis is high, buparvaquone resistance is widespread, and vaccine protection is poor in the field. Better understanding is, therefore, needed of the factors that influence the genetics of T. annulata populations both within its hosts and in its overall populations. Here we utilise a panel of six satellites and a mitochondrial cytochrome b marker to explore the multiplicity of T. annulata infection and patterns of emergence and spread of different parasite genotypes. Parasite materials were collected from infected animals in defined regions, where water buffalo and cattle are kept together. Our results show that T. annulata is genetically more diverse in cattle-than in water buffalo-derived populations (the mean numbers of unique satellite alleles were 13.3 and 1.8 and numbers of unique cytochrome b locus alleles were 65 and 27 in cattle- and water buffalo-derived populations, respectively). The data show a high level of genetic diversity among the individual host-derived populations (the overall heterozygosity (He) indices were 0.912 and 0.931 in cattle, and 0.874 and 0.861 in buffalo, based on satellite and cytochrome b loci, respectively). When considered in the context of high parasite transmission rates and frequent animal movements between different regions, the predominance of multiple T. annulata genotypes, with multiple introductions of infection in the hosts from which the parasite populations were derived, may have practical implications for the spread of parasite genetic adaptations; such as those conferring vaccine cross-protection against different strains affecting cattle and buffalo, or resistance to antiprotozoal drugs
Remodeling of endothelial function in atherosclerotic mice overexpressing endothelin-1 restricted to endothelium
No full text
