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Streptococci are well-known opportunistic bacterial abortifacients in mares. Colonization of the pregnant uterus is considered to happen after transcervical migration of bacteria from the lower genital tract mucosa. Streptococcus ovis is a pathogen mainly associated with inflammatory lesions in sheep. This species has not been reported in association with disease in horses. In the present case, S. ovis was isolated in monoculture from the lung of an 8-months-old equine fetus and was associated with development of acute suppurative bronchopneumonia, umbilical cord cellulitis and placentitis in the cervical star region of the allantochorion. The mare had been in a pasture together with sheep. One week prior to abortion, a double-guarded uterine swab had been inserted into the cervical canal by a veterinarian, who was unaware of the mare being pregnant. This probably damaged the cervical mucus plug thus allowing S. ovis bacteria to pass the cervical canal and colonize the placenta., Competing Interests: Declaration of competing interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Insulin-like growth factor binding-protein 2 (IGFBP-2) was originally identified as an IGF-carrier, governing IGF half-life, tissue accessibility and biological effects. Later, IGFBP-2 was discovered to possess IGF-independent effects. IGFBP-2 circulates in several forms, as free protein, complexed with IGF-I or IGF-II, or as IGFBP-2 fragments. The various IGFBP-2 forms are all included when measuring serum IGFBP-2 concentrations by immunoassay (i.e., immunoreactive (ir-)IGFBP-2). In this study, we describe a novel method to measure the amount of IGF that circulates bound to IGFBP-2., Method: IGFBP-2 was immunoprecipitated from human serum using magnetic beads, which were subsequently eluted by acidification. After neutralization, eluates were assayed for ir-IGFBP-2, IGF-I and IGF-II and compared to serum concentrations. This allowed measurement of IGFBP-2-compexed IGF-I and IGF-II, respectively. To test the method clinically, serum from 146 patients with lung cancer, 151 patients with non-cancer pulmonary diseases and 28 healthy controls were analyzed., Results: We immuno-precipitated 97 ± 3.3% of serum IGFBP-2 and recovered > 75% of IGFBP-2-complexed IGFs, with intra- and inter-assay coefficient of variations (CVs) averaging < 5% and < 13%, respectively. No co-precipitation with IGFBP-1, -3 or - 4 was detected. Serum levels of ir-IGFBP-2 (median [25;75%]) differed between groups (cancer patients vs. non-cancer patients vs. healthy controls): 342 [260;480] vs. 262 [189;388] vs. 190 [141;269] μg/l (p < .0001). In parallel with this, concentrations of IGF-II carried by IGFBP-2 averaged: 45.0 [33.3;52.5] vs. 34.2 [25.4;46.1] vs. 19.8 [14.1;26.0] μg/l (p < .0001), and concentrations of IGF-I 8.0 [5.2;11.8] vs. 5.4 [3.6;7.3] vs. 7.0 [3.8;13.0] μg/l (p < .0001). Thus, IGFBP-2 carried more IGF-II than IGF-I in all groups (p < .0001). When expressed relative to IGF-concentrations, IGFBP-2 carried 9.0 [5.3;15.5] % of the IGF-I and 4.8 [2.9;5.8] % of the IGF-II in serum from healthy subjects. Notably, in patients, IGFBP-2 carried relatively less IGF-I, but more IGF-II (p < .0001)., Conclusion: Using our novel assay, we demonstrate: that IGFBP-2 carries ≈10% of circulating IGF-I and ≈5% of circulating IGF-II in healthy subjects; that IGF-II is the primary ligand for IGFBP-2; and that IGFBP-2 carries even more IGF-II in patients than in healthy subjects. Thus, our assay may provide information on IGFBP-2 beyond what is achievable by simply measuring ir-IGFBP-2., Competing Interests: Declaration of Competing Interest Jan Frystyk, who is co-authoring this paper, also serves as Editor-in-Chief of Growth Hormone and IGF Research. However, this has not influenced on the handling of the paper, which has been subjected to the Journal's usual procedures. Thus, the peer review process has been handled independently of Jan Frystyk, who has been blinded to the review process. The remaining authors have nothing to disclose., (Copyright © 2020. Published by Elsevier Ltd.)

Several cauliflower-like alopecic masses arose on the head of an otherwise healthy, full-term newborn Jersey × Belgian blue heifer, which was humanely destroyed shortly after birth due to the severity of the skin lesions. Microscopically, the masses were composed of multiple papillary projections displaying well-differentiated sebaceous glands surrounded by a moderate number of well-developed sweat glands, as well as embryonic and fully developed, but dysplastic hair follicles. Thick branching connective tissue stalks supported these adnexal components. The papillated surface, the predominance of sebaceous glands, the presence of embryonic hair follicles and the well-differentiated sweat glands were compatible with nevus sebaceous, a rare form of cutaneous hamartoma described in man, dogs, cats and cattle. However, the cauliflower-like growth pattern, the presence of supportive thick branching connective tissue stalks and the relative abundance of dysplastic hair follicles in association with nevus sebaceous has not been described in the human or veterinary literature. A diagnosis of panadnexal papillomatous hamartoma was made in this case., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Pyometra is a common disease of cattle that causes infertility and thereby financial losses to the cattle industry. Bacteria involved in the development and progression of pyometra have been investigated by microbial culture but their tissue invading abilities, which is an important aspect of bacterial pathogenicity and development of lesions, have not been investigated. Bacterial invasion of the uterus and oviducts was studied in 21 cows diagnosed with pyometra at the time of slaughter by applying fluorescence in situ hybridization using probes targeting 16S ribosomal RNA of Fusobacterium necrophorum, Porphyromonas levii, Trueperella pyogenes and the overall bacterial domain Bacteria. Fusobacterium necrophorum and P. levii were found to invade the endometrium, especially if the endometrium was ulcerated, and penetrated deep into the lamina propria. These species co-localized within the tissue thus indicating a synergism. Trueperella pyogenes did not invade the uterine tissue. In addition to endometrial lesions, most cows with pyometra also had salpingitis but without significant bacterial invasion of the oviductal wall., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate bacterial invasiveness of the bovine endometrium during the postpartum period. Fluorescence in situ hybridization was applied to endometrial biopsies using probes for Fusobacterium necrophorum, Porphyromonas levii, Trueperella pyogenes, Escherichia coli and a probe for bacteria in general (the overall domain Bacteria) to determine their tissue localization. Holstein cows were sampled at three time points postpartum (T1: 4-12 days postpartum, T2: 24-32 days postpartum and T3: 46-54 days postpartum). At T1, cows were clinically scored as having a uterine infection based on presence of a brownish, fetid vaginal discharge or as normal if having normal lochia. An endometrial biopsy was taken from all cows at T1 (n = 57). Endometrial biopsies were taken from the same cows at T2 and T3 if allowed by the size of the cervical canal and if the cow had not been inseminated. Fifty and 39 biopsies were obtained at T2 and T3, respectively. The biopsies were evaluated for inflammation and for presence and localization of bacteria. When analyzed by the probe for the entire domain Bacteria, bacteria were found in most biopsies irrespectively of time (T1: 79.0%, T2: 82.0%, T3: 89.7%). Fusobacterium necrophorum and Porphyromonas levii were often present in the endometrium at T1 (61.1% and 47.8%, respectively), but the prevalence decreased significantly over time. Trueperella pyogenes and Escherichia coli were less prevalent at T1 (8.8% and 10.5%, respectively) and their prevalence also decreased significantly over time. Fusobacterium necrophorum and Porphyromonas levii were often co-localized intraepithelially or in the lamina propria. Trueperella pyogenes and Escherichia coli were located only on the endometrial surface. Due to the high prevalence of tissue invasiveness, these findings emphasize the importance of Fusobacterium necrophorum and Porphyromonas levii in postpartum uterine disease of cattle and indicate that tissue invasiveness is an important aspect of the pathogenesis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Left-sided valvular endocarditis (LSVE) is a common finding in slaughter pigs. The lesion is often associated with renal thromboembolism, but information on embolization to other organs is sparse. This study focuses on the presence and type of endocarditis-associated brain lesions (EABLs). The brains of 20 slaughter pigs with spontaneously arising LSVE and 11 controls were examined by sectioning half of a formalin-fixed brain into 4mm slices for histological examination. The aetiology of the endocarditis was determined by bacteriological and, in some cases, by fluorescence in-situ hybridization examinations. These examinations identified 11 cases of Streptococcus suis, six cases of Erysipelothrix rhusiopathiae, one Streptococcus spp. and two cases that remained aetiologically undetermined. One of the S. suis cases had a dual infection with S. suis in the aortic valve lesions and Streptococcus dysgalactiae subsp. equisimilis in the atrioventricular valve lesions. Renal infarcts were present in eight cases. Focal encephalitis was found in 12 cases, with the number of lesions ranging from one to 11. Most pigs had less than four microscopical lesions. Acute lesions were characterized by focal microabscesses without observable bacteria. Chronic lesions were characterized by astrocytosis and focal accumulation of mononuclear leucocytes. An infarct was observed in one animal. Perivascular inflammation was seen in 14 cases, mostly as two or three lesions, while focal leptomeningitis was found in eight cases. EABLs are therefore common in slaughter pigs with LSVE. The number of lesions per animal is small, which may explain the limited attention paid to this sequela of LSVE. EABLs have rarely been reported in domestic animals and mostly in patients with neurological signs. The frequent occurrence of EABLs in slaughter pigs suggests that this pathology should be investigated in other animal species with LSVE., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The intestinal bacterium Lawsonia intracellularis, the cause of proliferative enteropathy (PE) in pigs, is believed to infect mitotically active epithelial cells of the intestinal crypts and then multiply and spread in these cells as they divide. Further spread of infection is thought to occur by shedding of bacteria from infected crypts followed by infection of new crypts. The early stages of the pathogenesis of PE, from 0 to 48 hours post-infection (hpi), have not been studied in vivo. In the present study pigs were inoculated with L. intracellularis and killed from 12 hpi to 5 days post-infection (dpi). The localization of L. intracellularis was determined immunohistochemically and by fluorescence in-situ hybridization. At 12 hpi L. intracellularis was found within epithelial cells at the tips of villi, indicating infection of a range of epithelial cells including mature differentiated enterocytes. Furthermore, early invasion of the intestinal connective tissue was observed; with the presence of single bacteria in the lamina propria 12 hpi, and with a further spread of bacteria in the lamina propria observed at 5 dpi, suggesting an active role for the lamina propria in the course of infection., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Outbreaks of digital necrobacillosis in Norwegian wild tundra reindeer (Rangifer tarandus tarandus) are described. The outbreaks occurred in late summer and autumn 2007 and 2008, subsequent to periods with an unusually high number of days with precipitation and high air temperature. Lesions were generally restricted to one foot and the disease incidence was highest in calves. Single limbs from 20 animals and six whole carcasses were submitted for laboratory examination. Gross lesions were characterized by swelling of the fetlock to coronary band area and cutaneous sinus tracts with sparse discharge of pus. Subcutaneous tissue was inflamed and oedematous with focal necrosis. Tendons, tendon sheaths, joints and periosteum of the digital bones were often affected. Animals shot during winter showed severe chronic periostitis and osteomyelitis and necrotizing deforming arthritis. Microscopically, skin lesions were characterized by deep ulcers with centrally located necrotic tissue, bordered by a zone of oedema and intense inflammation with granulation tissue and fibrosis. Necrosis, suppurative inflammation and oedema were found in the synovial membranes, tendons and tendon sheaths. Digital bone lesions were characterized by necrosis, fibrosis and extensive bone proliferation. Vasculitis and thrombosis were common in all lesions. Elongate filamentous gram-negative bacteria in necrotic lesions from all animals were identified as Fusobacterium necrophorum by fluorescence in-situ hybridization. F. necrophorum was cultured from the foot lesions of six animals. Five of these isolates were examined by 16S rRNA sequencing. The sequences were identical and differed from all other strains listed in GenBank. These results are consistent with circulation of a reindeer-adapted pathogenic strain of F. necrophorum in the wild reindeer population, causing outbreaks of digital necrobacillosis following warm and humid summers., ((c) 2010 Elsevier Ltd. All rights reserved.)

The association of Fusobacterium necrophorum with late term abortion in sheep is reported. The bacterium was not culturable, but was identified in five cases by fluorescence in-situ hybridization (FISH) with an oligonucleotide probe specifically targeting 16S rRNA in F. necrophorum. Gross lesions were found in several tissues. Histologically, placental lesions were characterized by locally diffuse infiltration of neutrophils, closely associated with abundant small Gram-negative and FISH-positive rods, thrombosis and necrosis. Lesions in the fetal-maternal interface were multifocal and consisted of villous necrosis and suppurative inflammation. Spread to the fetus from the placenta appeared to occur in two ways. Some fetuses had multifocal necrotizing hepatitis consistent with haematogenous spread through the umbilical vein; further dissemination to other organs occurred. Transplacental spread and infection of the fetus through the amniotic fluid was characterized by development of multifocal suppurative dermatitis and suppurative bronchopneumonia. Localization of FISH-positive bacteria in necrotic lesions was restricted to the periphery. F. necrophorum would seem to have been unrecognized previously as a cause of abortion. The value of culture-independent diagnostic methods is emphasized.

In 1998 and 2002, European bat lyssavirus type-1 (EBLV-1) was demonstrated in brain tissue of five Danish sheep suffering from neurological disorders. Four of the five sheep also had encephalic listeriosis. The animals originated from four flocks on pastures within a limited area of western Jutland. In a serological investigation in two of the herds, from which three of the diseased animals originated, EBLV-1 neutralizing antibodies were detected in only one of 69 sheep. In follow-up surveys, 2110 sheep sera collected at Danish slaughterhouses during 2000 were all negative for EBLV-1-antibodies, and EBLV-1 was not demonstrated in 87 ruminants displaying neurological symptoms. To investigate the pathogenic effects of EBLV-1, four sheep were inoculated intralabially with either brain material from one of the naturally infected sheep or virus isolated from the same sheep. These animals developed EBLV-1 neutralizing antibodies at 5-9 weeks post-inoculation but did not exhibit neurological signs during a 33-week observation period. It was speculated that the immune response prevented viral dissemination to the brain, resulting in an abortive peripheral infection. It was concluded that EBLV-1 can infect sheep under natural conditions as an incidental event.

A study was performed to characterize dark brown or black discoloured kidneys ("black kidneys") in Danish slaughter cattle and to investigate the aetiology and pathogenesis. In 133 939 cattle entering four abattoirs, 359 cases of "black kidneys" were recorded. Of these, 57 cases were submitted for macroscopical, microscopical, and ultrastructural examination. A pigment with characteristics similar to those of lipofuscin was found in secondary lysosomes in epithelial cells of the proximal tubules. Pigment accumulation was the cause of discoloration, with a positive correlation between the discoloration of the renal cortex and the degree of pigment accumulation. Cases occurred only in cattle of the Holstein breed or the Red Danish Dairy breed and mainly in animals aged 3 years or older. In these breeds, prevalences of 0.44% and 2.51% were found, respectively. Epidemiological analyses indicated that affected animals aged 4.5 to 6.5 years or 7.5 to 8.5 years were culled more frequently than unaffected cattle. Epidemiological and genealogical analyses strongly indicated a genetic aetiology with simple autosomal recessive inheritance.