Proof of concept of a new plasma complement Factor H from waste plasma fraction.

Introduction: Complement factor H (FH) is a major regulator of the complement alternative pathway, its mutations predispose to an uncontrolled activation in the kidney and on blood cells and to secondary C3 deficiency. Plasma exchange has been used to correct for FH deficiency and although the therapeutic potential of purified FH has been suggested by experiments in animal models, a clinical approved FH concentrate is not yet available. We aimed to develop a purification process of FH from a waste fraction rather than whole plasma allowing a more efficient and ethical use of blood and plasma donations.

The art of establishing mineral tolerances of dogs and cats.

For over six decades, nutritional science has provided well-developed, peer-reviewed nutrient recommendations to support the health of dogs and cats. These guidelines are updated based on new scientifically valid research and appropriate peer-review. Recent regulatory and scientific positions around health issues have resulted in strong opinions and desires for rapid regulatory action surrounding mineral nutrition, but with limited and conflicting scientific evidence.

HUS and TTP: traversing the disease and the age spectrum.

Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenia purpura (TTP) are rare diseases sharing a common pathological feature, thrombotic microangiopathy (TMA). TMA is characterized by microvascular thrombosis with consequent thrombocytopenia, microangiopathic hemolytic anemia and/or multiorgan dysfunction. In the past, the distinction between HUS and TTP was predominantly based on clinical grounds.

Liver factor B silencing to cure C3 glomerulopathy: Evidence from a mouse model of complement dysregulation.

Uncontrolled activation of the alternative pathway (AP) of complement, due to genetic and/or acquired defects, plays a primary pathogenetic role in C3 glomerulopathy (C3G), a rare and heterogeneous disease characterised by predominant C3 fragment deposition within the glomerulus, as well as glomerular damage. There are currently no approved disease-specific treatments for C3G, but new drugs that directly counteract AP dysregulation, targeting components of the pathway, have opened promising new perspectives for managing the disease. Complement factor B (FB), which is primarily synthesised by hepatocytes, is a key component of the AP, as it drives the central amplification loop of the complement system.

Mutation Analysis of PKD1 and PKD2 Genes in a Large Italian Cohort Reveals Novel Pathogenic Variants Including a Novel Complex Rearrangement.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidney. It occurs in adulthood but is also rarely diagnosed in early childhood. The majority of the disease-causing variants observed in ADPKD patients are in two genes: PKD1 and PKD2.

Substrate degradation and postbiotic analysis of alternative fiber ingredients fermented using an in vitro canine fecal inoculum model.

Many fiber ingredients are used by the pet food industry; however, little data are available regarding the fermentation characteristics of alternative fibers currently being used. The objectives of this study were to determine organic matter disappearance (OMD) and postbiotic production from various fruit and vegetable fiber sources using an in vitro dog fecal inoculum model. Apple pomace (AP), blueberry pomace (BP), cranberry pomace (CP), tomato pomace (TP), and pea fiber (PF) were used as experimental treatments.

and structural variants in atypical Hemolytic Uremic Syndrome: Prevalence, genomic characterization and impact on outcome.

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare disease that manifests with microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, and is associated with dysregulation of the alternative complement pathway. The chromosomal region including and is rich in repeated sequences, favoring genomic rearrangements that have been reported in several patients with aHUS. However, there are limited data on the prevalence of uncommon genomic rearrangements in aHUS and their impact on disease onset and outcomes.

Fresh Food Consumption Increases Microbiome Diversity and Promotes Changes in Bacteria Composition on the Skin of Pet Dogs Compared to Dry Foods.

The skin is the first barrier the body has to protect itself from the environment. There are several bacteria that populate the skin, and their composition may change throughout the dog's life due to several factors, such as environmental changes and diseases. The objective of this research was to determine the skin microbiome changes due to a change in diet on healthy pet dogs.

Mycoplasma pneumoniae Infection Associated with Anti-Factor H Autoantibodies in Atypical Hemolytic Uremic Syndrome.

Hemolytic uremic syndrome (HUS) is a rare disease characterized by hemolytic anemia, thrombocytopenia, and renal impairment mostly triggered by strains of Shiga-like toxin-producing Escherichia coli (STEC-HUS). A rarer form of HUS, defined as atypical HUS (aHUS), is associated with genetic or acquired dysregulation of the alternative pathway of the complement system and presents a poorer prognosis than STEC-HUS. Factor H autoantibodies (anti-FHs) have been reported in aHUS in 5-11% of cases and are strongly associated with the homozygous deletion of CFHR3-CFHR1 genes.

SARS-CoV-2 Spike Protein 1 Activates Microvascular Endothelial Cells and Complement System Leading to Platelet Aggregation.

Microvascular thrombosis is associated with multiorgan failure and mortality in coronavirus disease 2019 (COVID-19). Although thrombotic complications may be ascribed to the ability of SARS-CoV-2 to infect and replicate in endothelial cells, it has been poorly investigated whether, in the complexity of viral infection in the human host, specific viral elements alone can induce endothelial damage. Detection of circulating spike protein in the sera of severe COVID-19 patients was evaluated by ELISA.

Therapeutic Small Interfering RNA Targeting Complement C3 in a Mouse Model of C3 Glomerulopathy.

Alternative pathway complement dysregulation with abnormal glomerular C3 deposits and glomerular damage is a key mechanism of pathology in C3 glomerulopathy (C3G). No disease-specific treatments are currently available for C3G. Therapeutics inhibiting complement are emerging as a potential strategy for the treatment of C3G.

and Copy Number Variations in C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis.

C3 Glomerulopathy (C3G) and Immune Complex-Mediated Membranoproliferative glomerulonephritis (IC-MPGN) are rare diseases characterized by glomerular deposition of C3 caused by dysregulation of the alternative pathway (AP) of complement. In approximately 20% of affected patients, dysregulation is driven by pathogenic variants in the two components of the AP C3 convertase, complement C3 () and Factor B (), or in complement Factor H () and Factor I (), two genes that encode complement regulators. Copy number variations (CNVs) involving the -related genes () that give rise to hybrid FHR proteins also have been described in a few C3G patients but not in IC-MPGN patients.

Amnion epithelial cells are an effective source of factor H and prevent kidney complement deposition in factor H-deficient mice.

Complement factor H (FH) is the main plasma regulator of the alternative pathway of complement. Genetic and acquired abnormalities in FH cause uncontrolled complement activation amplifying, with the consequent accumulation of complement components on the renal glomeruli. This leads to conditions such as C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS).

The effects of fiber source on extrusion processing parameters and kibble characteristics of dry cat foods.

Cellulose and beet pulp have been commonly used in the pet food industry to increase the dietary fiber content of cat foods. However, pet food companies seek alternatives to these so-called byproducts. Miscanthus grass is grown for its fiber content and may serve as an alternative to traditional fibrous ingredients.

A commercial grain-free diet does not decrease plasma amino acids and taurine status but increases bile acid excretion when fed to Labrador Retrievers.

Grain-free diets tend to have greater inclusions of pulses in contrast to grain-based diets. In 2018, the Food and Drug Administration (FDA) released a statement that grain-free diets may be related to the development of canine dilated cardiomyopathy (DCM). However, all dog foods met regulatory minimums for nutrient inclusion recommended by the Association of American Feed Controls Official.

The effects of diets varying in fibre sources on nutrient utilization, stool quality and hairball management in cats.

Pet food companies use fibrous ingredients in cat foods to aid weight and hairball management. Miscanthus grass could be an alternative novel fibre source for cat foods. The objectives of this work were to determine the effects of Miscanthus grass as a fibre source on nutrient utilization, stool quality and hairball management in cats.

Organic matter disappearance and production of short- and branched-chain fatty acids from selected fiber sources used in pet foods by a canine in vitro fermentation model1.

Dietary fibers can influence a dog's overall health, but high concentrations of soluble dietary fibers can cause soft stools. An in vitro model could be useful to predict the rate fibers are fermented once they reach the colon. Pet food companies are constantly searching for new ingredients to differentiate their products from competitors.

The effects on nutrient utilization and stool quality of Beagle dogs fed diets with beet pulp, cellulose, and Miscanthus grass12.

Dogs can benefit from dietary fibers. Traditionally, cellulose (CE) and beet pulp (BP) have been used by pet food companies as insoluble and soluble fiber sources. Miscanthus grass (MG) is a novel fiber ingredient made from Miscanthus giganteus, a C4 grass produced for its fiber content, but it has not been evaluated for dogs.

Effect of fiber source and particle size on chick performance and nutrient utilization.

The addition of fiber in chick feeds is known to dilute nutrients; as a result, this may reduce nutrient digestibility and performance. However, recent studies suggest that moderate inclusion of insoluble fibers (2 to 3%) may stimulate gizzard development, which could result in better nutrient utilization and chick growth. The previous fiber sources evaluated were subject to wide fluctuation in their nutritional and chemical composition due to variation in processing.

Rare Functional Variants in Complement Genes and Anti-FH Autoantibodies-Associated aHUS.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal failure. It is caused by genetic or acquired defects of the complement alternative pathway. Factor H autoantibodies (anti-FHs) have been reported in 10% of aHUS patients and are associated with the deficiency of factor H-related 1 (FHR1).

An Ex Vivo Test of Complement Activation on Endothelium for Individualized Eculizumab Therapy in Hemolytic Uremic Syndrome.

Rationale & Objective: Although primary atypical hemolytic uremic syndrome (aHUS) is associated with abnormalities in complement genes and antibodies to complement factor H, the role of complement in secondary aHUS remains debatable. We evaluated the usefulness of an ex vivo test to: (1) detect complement activation within the endothelium in primary and secondary aHUS, (2) differentiate active disease from remission, (3) monitor the effectiveness of eculizumab therapy, and (4) identify relapses during eculizumab dosage tapering and after discontinuation of treatment.

Study Design: Case series.