Microscopic changes in the kidneys of cows infected with Leptospira sp.

Ukhovskyi, V. V.; Борисевич, Б В; Kulykova, Vlada; Żmudzki, J.; Jabłoński, Artur

doi:10.2478/bvip-2014-0079

Cited by 2 publications

(2 citation statements)

References 16 publications

(11 reference statements)

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“…Apart from immune protection against microbes, these epithelial cells also strongly express ACE-2 [17], which is known for its Surprisingly, KEPTIDE-treatment prevented the degeneration of these epithelial cells in virusinfected K18-hACE2 mice. We also observed increased vacuolization in kidney cortex with glomerular swelling after twenty-four hours of virus treatment, which is frequently observed in degenerative kidney [19,20]. ACIS KEPTIDE significantly protected the kidney parenchyma with decreased vacuolization and also protected glomerular swelling.…”

Section: Acis Keptide Stimulates the Internalization And Downregulatisupporting

confidence: 67%

Intranasal Administration of ACIS KEPTIDE™ Prevents SARS-CoV2-Induced Acute Toxicity in K18-hACE2 Humanized Mouse Model of COVID-19: A Mechanistic Insight for the Prophylactic Role of KEPTIDE™ in COVID-19

Gottschalk¹,

Keating²,

Kesler³

et al. 2020

Preprint

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Previously, we have demonstrated that ACIS KEPTIDE™, a chemically modified peptide, selectively binds to ACE-2 receptor and prevents the entry of SARS-CoV2 virions in vitro in primate kidney Cells. However, it is not known if ACIS KEPTIDE™ attenuates the entry of SARS-CoV2 virus in vivo in lung and kidney tissues, protects health, and prevent death once applied through intranasal route. In our current manuscript, we demonstrated that the intranasal administration of SARS-CoV2 (1*106) strongly induced the expression of ACE-2, promoted the entry of virions into the lung and kidney cells, caused acute histopathological toxicities, and mortality (28%). Interestingly, thirty-minutes of pre-treatment with 50 μg/Kg Body weight ACIS normalized the expression of ACE-2 via receptor internalization, strongly mitigated that viral entry, and prevented mortality suggesting its prospect as a prophylactic therapy in the treatment of COVID-19. On the contrary, the peptide backbone of ACIS was unable to normalize the expression of ACE-2, failed to improve the health vital signs and histopathological abnormalities. In summary, our results suggest that ACIS is a potential vaccine-alternative, prophylactic agent that prevents entry of SARS-CoV2 in vivo, significantly improves respiratory health and also dramatically prevents acute mortality in K18-hACE2 humanized mice.HighlightsACIS KEPTIDE stimulates the internalization of ACE-2 receptor (Fig. 2) and buffers the membrane localization of ACE-2 receptors (Fig. 2, 6 & 8). Intranasal inoculation of SARS-CoV2 upregulates the expression of ACE-2 in lung epithelium (Fig.6) and kidney tubular cells (Fig.8). ACIS KEPTIDE normalizes the expression of ACE-2 in the kidney tubular cells of virus-treated K18-hACE2mice (Fig. 8).ACIS KEPTIDE™ completely prevents the entry of SARS-CoV2 in Bronchiolar epithelium (Fig.6), alveolar parenchyma (Fig. 6), and kidney tubular cells (Fig.8).ACIS KEPTIDE™ improves the pulmonary (Fig. 5) and renal pathological changes (Fig. 7) caused by the SARS-CoV2 virus insult.Intranasal administration of 0.05% Beta-propiolactone (βPL)-inactivated SARS-CoV2 (1 *106) causes significant death (28%) in K18-hACE2 humanized mice after 24 hrs of intranasal inoculation (Supplemental videos) suggesting that SARS-CoV2 does not require its infective properties and genetic mechanism to be functional to cause mortality.The peptide backbone of ACIS KEPTIDE™ provides much less and insignificant protection in the prevention of pathological changes in Lungs (Fig.5 & 6) and Kidney (Fig.7 & 8). Peptide failed to normalize the upscaled expression of ACE-2 in kidney tubular cells (Fig.8) of SARS-CoV2-treated K18-hACE2 mice.

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Section: Acis Keptide Stimulates the Internalization And Downregulatisupporting

confidence: 67%

Intranasal Administration of ACIS KEPTIDE™ Prevents SARS-CoV2-Induced Acute Toxicity in K18-hACE2 Humanized Mouse Model of COVID-19: A Mechanistic Insight for the Prophylactic Role of KEPTIDE™ in COVID-19

Gottschalk¹,

Keating²,

Kesler³

et al. 2020

Preprint

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“…Carrier animals with chronic renal infection, mainly rats, dogs, cattle, horses, sheep, goats and pigs, are a constant reservoir of Leptospira in nature. These animals can excrete Leptospira in their urine for many years (Ukhovskyi, 2014). Dogs are a fairly common source of human infection (Adler & de la Peña Moctezuma, 2010;Narkkul et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Epizootological and epidemiological aspects of leptospirosis in Ukraine for the period 2003–2022

Korniienko,

Ukhovskyi,

Moroz

et al. 2023

Regul. Mech. Biosyst.

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Zoonotic leptospirosis is an infectious disease caused by pathogenic Leptospira bacteria that can be transmitted from animals to humans. Animals, especially wild and domestic mammals, are reservoir hosts that carry and excrete the bacteria in their urine. A retrospective analysis of the incidence of leptospirosis in animals and humans in Ukraine from 2003 to 2022 was conducted based on reports from regional state laboratories of veterinary medicine and the Center for Public Health. GIS mapping was used to analyze and visualize the data. The incidence and prevalence of leptospirosis among different animal species, including farm, domestic and wild animals, were analyzed. These studies included a retrospective analysis of blood serum samples from different animal species for leptospirosis and analysis of the results to determine the level of seropositivity. The study analyzed a total of 6,543,934 samples, with an overall seropositivity rate of 3.3%. Among cattle, 4.1% of the samples were positive. For pigs, 2.1% were positive. Horses had a seropositivity rate of 7.9%, while dogs and cats had seropositivity rates of 17.5% and 13.1% respectively. Wild boars showed a positivity rate of 2.2%. The number of seropositive animals of different species in Ukraine showed different dynamics from 2003 to 2022. The highest number of positive cases was found among cattle, pigs and horses. However, the number of positive cases decreased significantly after 2015, which coincides with a significant reduction in the number of farm animals. Trends of increasing seropositivity among dogs and cats in the period 2007–2015 indicate that these species are also active carriers of Leptospira, as are the leading agricultural species. Wildlife species with stable seropositivity serve as both sources and reservoirs of Leptospira. Wild pigs are becoming the main bacterial carriers in all regions of Ukraine. There is a marked disproportion between the number of positive cases among farm animals and wildlife, indicating that seropositivity in these populations exists largely autonomously. A total of 7,937 people were infected in Ukraine between 2003 and 2022. Certain regions, such as Lviv, Kherson, Kyiv, Mykolaiv, and Vinnytsia, account for a larger share of the total number of cases, ranging from 4.8% to 7.3%. The incidence of human leptospirosis has fluctuated over the years, peaking at 473 cases in 2014, followed by a decline: 301 cases in 2015, 323 cases in 2016 and 330 cases in 2017, and in subsequent years the number of cases remained relatively stable, ranging from 142 to 295 cases per year. The study emphasizes the need to improve preventive measures and raise public awareness of the disease, especially in rural areas. It is important to adopt a comprehensive interdisciplinary approach involving collaboration between veterinary medicine, public health and environmental authorities to better understand and address the complexities of leptospirosis transmission and reduce its impact on animal and human health.

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Microscopic changes in the kidneys of cows infected with Leptospira sp.

Cited by 2 publications

References 16 publications

Intranasal Administration of ACIS KEPTIDE™ Prevents SARS-CoV2-Induced Acute Toxicity in K18-hACE2 Humanized Mouse Model of COVID-19: A Mechanistic Insight for the Prophylactic Role of KEPTIDE™ in COVID-19

Intranasal Administration of ACIS KEPTIDE™ Prevents SARS-CoV2-Induced Acute Toxicity in K18-hACE2 Humanized Mouse Model of COVID-19: A Mechanistic Insight for the Prophylactic Role of KEPTIDE™ in COVID-19

Epizootological and epidemiological aspects of leptospirosis in Ukraine for the period 2003–2022

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