In this article, we describe a new approach that allows the prediction of the performance of a large-scale integrated process for the primary recovery of a therapeutic antibody from an analysis of the individual unit operations and their interactions in an ultra scale-down mimic of the process. The recovery process consisted of four distinct unit operations. Using the new approach we defined the important engineering parameters in each operation that impacted the overall recovery process and in each case verified its effect by a combination of modelling and experimentation. Immunoglobulins were precipitated from large volumes of dilute blood plasma and the precipitated flocs were recovered by centrifugal separation from the liquor containing contaminating proteins, including albumin. The fluid mechanical forces acting on the precipitate and the time of exposure to these forces were used to define a time-integrated fluid stress. This was used as a scaling factor to predict the properties of the precipitated flocs at large scale. In the case of centrifugation, the performance of a full-scale disc stack centrifuge was predicted. This was achieved from a computational fluid dynamics (CFD) analysis of the flow field in the centrifuge coupled with experimental data obtained from the precipitated immunoglobulin flocs using the scale-down precipitation tank, a rotating shear device, and a standard swing-out rotor centrifuge operating under defined conditions. In this way, the performance of the individual unit operations, and their linkage, was successfully analysed from a combination of modelling and experiments. These experiments required only millilitre quantities of the process material. The overall performance of the large-scale process was predicted by tracking the changes in physical and biological properties of the key components in the system, including the size distribution of the antibody precipitates and antibody activity through the individual unit operations in the ultra scale-down process flowsheet.
The first case of human babesiosis was reported in the literature in 1957. The clinical disease has sporadically occurred as rare case reports in North America and Europe in the subsequent decades. Since the new millennium, especially in the last decade, many more cases have apparently appeared not only in these regions but also in Asia, South America, and Africa. More than 20,000 cases of human babesiosis have been reported in North America alone. In several cross-sectional surveys, exposure to Babesia spp. has been demonstrated within urban and rural human populations with clinical babesiosis reported in both immunocompromised and immunocompetent humans. This review serves to highlight the widespread distribution of these tick-borne pathogens in humans, their tick vectors in readily accessible environments such as parks and recreational areas, and their phylogenetic relationships.
Phytophthora root rot (PRR) of avocado, caused by Phytophthora cinnamomi, is a significant threat to sustainable production wherever the crop is grown. Resistant rootstocks in combination with phosphite applications are the most effective options for managing this disease. Recently, the mechanisms underpinning PRR resistance have been investigated by the avocado community. Here, biochemical assays and confocal and scanning electron microscopy were used to investigate early defence responses in PRR resistant and ‐susceptible avocado rootstocks. Zoospore germination and subsequent hyphal growth for the pathogen were significantly inhibited on the surface of resistant avocado roots. When penetration occurred in the resistant R0.06 rootstock, callose was deposited in the epidermal cells, parenchyma and cortex of roots. In addition, β‐1,3‐glucanase was released early (6 h post‐inoculation, hpi) in response to the pathogen, followed by a significant increase in catalase by 24 hpi. In contrast, susceptible R0.12 roots responded only with the deposition of lignin and phenolic compounds incapable of impeding pathogen colonization. In this study, PRR resistance was attributed to a timely multilayered response to infection by P. cinnamomi.
Spirocerca lupi is a common cause of vomiting, regurgitation, and sudden death in dogs that live in tropical or subtropical regions. Sudden death due to aortic rupture may occur with no preceding clinical signs. The purpose of this prospective study was to compare radiographic and computed tomographic (CT) characteristics of aortic lesions in a cohort of 42 dogs with endoscopically confirmed spirocercosis. Dorsoventral and right lateral recumbent thoracic radiographic findings were compared with pre- and postcontrast thoracic CT findings. Aortic mineralization was detected using CT in 18/42 dogs (43%). Three dogs had faint diffuse aortic wall mineralization. Using CT as the reference standard, radiographs had a sensitivity and specificity of 6% and 96%, respectively, for detecting aortic mineralization. A total of 20 aortic aneurysms were detected using CT in 15/42 dogs (36%). Using CT as the reference standard, radiographs had a sensitivity and specificity of 86% and 56%, respectively, for detecting aortic aneurysms. Respiratory motion, aortic displacement by esophageal masses and Spirocerca nodules adjacent to the aorta mimicked aneurysm formation on radiographs. Aortic thrombi were seen in two dogs in postcontrast CT images. Findings from this study indicated that aortic mineralization and aneurysm formation are common in dogs with spirocercosis. Findings also supported the use of pre- and postcontrast CT as effective methods for detecting and characterizing these lesions.
Several faecal examination techniques have shown variable sensitivity in demonstrating Spirocerca lupi (S. lupi) eggs. The objective of this study was to determine which faecal examination technique, including a novel modified centrifugal flotation technique, was most sensitive to diagnose spirocercosis. Ten coproscopic examinations were performed on faeces collected from 33 dogs confirmed endoscopically to have spirocercosis. The tests included a direct faecal examination, a faecal sedimentation/flotation test, 4 direct faecal flotations and 4 modified faecal centrifugal flotations. These latter 2 flotation tests utilised 4 different faecal flotation solutions:NaNO3 (SG 1.22),MgSO4 (SG 1.29),ZnSO4 (SG 1.30) and sugar (SG 1.27). The sensitivity of the tests ranged between 42 %and 67 %, with theNaNO3 solution showing the highest sensitivity in both the direct and modified-centrifugal flotations. The modified NaNO3 centrifugal method ranked 1st with the highest mean egg count (45.24±83), and was superior (i.e. higher egg count) and significantly different (P< 0.05) compared with the routine saturated sugar,ZnSO4 andMgSO4 flotation methods. The routine NaNO3 flotation method was also superior and significantly different (P < 0.05) compared with the routine ZnSO4 andMgSO4 flotation methods. Fifteen per cent (n=5) of dogs had neoplastic oesophageal nodules and a further 18 % (n = 6) had both neoplastic and non-neoplastic nodules. S. lupi eggs were demonstrated in 40%of dogs with neoplastic nodules only and 72.9 % of the dogs with non-neoplastic nodules. The mean egg count in the non-neoplastic group (61) was statistically greater (P = 0.02) than that of the neoplastic group (1). The results show that faecal examination using a NaNO3 solution is the most sensitive in the diagnosis of spirocercosis. The modified centrifugal flotation faecal method using this solution has the highest egg count. The study also found that dogs with neoplastic nodules shed significantly fewer eggs than dogs with non-neoplastic nodules
Theileriosis is a tick-borne disease caused by a piroplasma of the genus Theileria that can causeanaemia and thrombocytopenia. Its clinical importance for dogs’ remains poorly understood,as only some develop clinical signs. In this study, physical and laboratory findings, treatment and outcomes of six client-owned diseased dogs presented at the Onderstepoort Veterinary Academic Hospital are described retrospectively. In the dogs, Theileria species (n = 4)and Theileria equi (n = 2) were detected by a polymerase chain reaction (PCR)-reverse blothybridisation assay in blood samples, whilst PCR for Babesia, Anaplasma and Ehrlichia were negative. The most common physical findings were pale mucous membranes (five out of six dogs), bleeding tendencies (five out of six dogs) and lethargy (three out of six dogs). All dogs were thrombocytopenic [median 59.5 x 109/L (range 13–199)] and five out of six dogs were anaemic [median haematocrit 18% (range 5–32)]. Bone marrow core biopsies performed in two dogs showed myelofibrosis. Theileriosis was treated with imidocarb dipropionate and the suspected secondary immune-mediated haematological disorders with prednisolone and azathioprine. Five dogs achieved clinical cure and post-treatment PCR performed in three out of five dogs confirmed absence of circulating parasitaemia. An immune-mediated response to Theileria species is thought to result in anaemia and/or thrombocytopenia in diseased dogs with theileriosis. A bleeding tendency, most likely secondary to thrombocytopenia and/or thrombocytopathy, was the most significant clinical finding in these cases. The link between thrombocytopenia, anaemia and myelofibrosis in theileriosis requires further investigation and theileriosis should be considered a differential diagnosis for dogs presenting with anaemia and/or thrombocytopenia in endemic tick-borne disease areas.
Trichomonas tenax is a flagellated protozoan that inhabits the human and canine oral cavity in patients with poor oral hygiene and periodontal disease. The loop-mediated isothermal amplification (LAMP) assay could provide clinicians with a quick, cheap and reliable diagnostic test used for the detection of T. tenax in various settings. In this study, we aimed to develop a LAMP assay that can detect T. tenax with high sensitivity and specificity. A set of LAMP primers were specifically designed to detect the ITS and 5.8S rRNA gene of T. tenax. The newly developed LAMP assay was 1000 times more sensitive than conventional PCR. The limit of detection of the LAMP assay was 10 fg of genomic DNA, or 0.2–1 cell. Moreover, the LAMP assay was specific, resulting in no cross-reaction even with a closely related protozoan T. vaginalis or other microorganisms (Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, and Candida albicans) used. The present LAMP assay can be performed directly without prior DNA extraction, making the assay an easy, fast, cheap, specific and sensitive diagnostic tool for the detection of T. tenax at the point-of-care of both medical and veterinary clinics in developed and developing countries.
This longitudinal cross-sectional clinical study investigated the incidence of sialorrhoea in dogs with spirocercosis and determined whether breed, body weight and the extent of the oesophageal involvement was associated with this presentation. A retrospective analysis was performed on the medical records of 233 dogs and information pertaining to 65 dogs was collected as part of a prospective study. All the animals were client-owned. Patients from the retrospective study underwent thoracic radiography or oesophageal endoscopy to diagnose and characterise the infection and were placed on therapy with a macrocyclic lactone, whereas the patients in the prospective study had both radiography and endoscopy routinely performed and biopsies of the oesophageal nodules collected where possible. Tru-cut biopsies of affected salivary glands were taken in 10 of 13 patients demonstrating clinical signs of sialorrhoea and salivary gland enlargement. The entire salivary gland was sectioned in an additional three dogs with spirocercosis and no sialorrhoea that were presented for post mortem examination. Sialorrhoea was present in 33/298 cases (11%). Fox terrier breeds were over-represented in the patients with sialorrhoea, comprising 36% of cases, whereas they only comprised 1.5% of the patients without sialorrhoea (p < 0.001, chi squared test) and 5% of the combined group. Dogs weighing 12 kg or less were significantly over-represented in the sialorrhoea group, 69% versus 19.5% (p < 0.001, chi square test). Age was not significantly different between the two groups (p < 0.08, Mann-Whitney test). The number of oesophageal nodules per case was significantly higher in the non-sialorrhoea cases (p = 0.048, Mann-Whitney test). The prevalence of distal oesophageal and lower oesophageal sphincter involvement, and neoplastic transformation of the nodules were not statistically different between the two groups. None of the fox terriers in either group showed neoplastic transformation of the parasitic nodules even though they were over-represented as a breed. Mandibular salivary glands were affected in 86% of cases showing sialorrhoea. Histopathology revealed acinar hyperplasia in all cases with concurrent necrosis detected in only two cases.Sialorrhoea and salivary gland enlargement has an incidence of 11% (33/298 cases) in canine spirocercosis. Small breeds (≤ 12 kg) and particularly fox terrier breeds are over-represented in the group demonstrating sialorrhoea and this appeared to be the only risk factor.The conclusion was that sialorrhoea secondary to canine spirocercosis occurs frequently and its presence should prompt further investigation for oesophageal and gastro-intestinal disease. Severely affected patients can be managed with phenobarbitone to control the dysphagia in addition to the routine macrocyclic lactones treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.