Open-label, single-center, clinical study evaluating the safety, tolerability and clinical effects of pentosan polysulfate sodium in subjects with mucopolysaccharidosis I.

Lysosomal enzyme deficiency in mucopolysaccharidosis (MPS) I results in glycosaminoglycan (GAG) accumulation leading to pain and limited physical function. Disease-modifying treatments for MPS I, enzyme replacement, and hematopoietic stem cell therapy (HSCT), do not completely resolve MPS I symptoms, particularly skeletal manifestations. The GAG reduction, anti-inflammatory, analgesic, and tissue remodeling properties of pentosan polysulfate sodium (PPS) may provide disease-modifying treatment for musculoskeletal symptoms and joint inflammation in MPS I following ERT and/or HSCT.

Intrathecal enzyme replacement therapy reverses cognitive decline in mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disease that seriously affects the brain. Severity of neurocognitive symptoms in attenuated MPS subtype (MPS IA) broadly varies partially, due to restricted permeability of blood-brain barrier (BBB) which limits treatment effects of intravenously applied α-L-iduronidase (rhIDU) enzyme. Intrathecal (IT) rhIDU application as a possible solution to circumvent BBB improved brain outcomes in canine models; therefore, our study quantifies effects of IT rhIDU on brain structure and function in an MPS IA patient with previous progressive cognitive decline.

Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA.

Mucopolysaccharidosis type IVA (MPS IVA) was described in 1929 by Luis Morquio from Uruguay and James Brailsford from England, and was later found as an autosomal recessive lysosomal storage disease. MPS IVA is caused by mutations in the gene encoding the enzyme, N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Reduced GALNS activity results in impaired catabolism of two glycosaminoglycans (GAGs), chondroitin-6-sulfate (C6S) and keratan sulfate (KS).

Pre-freeze bull sperm head morphometry related to post-thaw fertility.

Artificial insemination using cryopreserved semen is a common management tool of the contemporary livestock producer. The ability to determine post-thaw fertility from pre-freeze sperm function parameters would be of major benefit to producers. In this study computer-aided sperm head morphometry was used to determine whether there is any association between pre-freeze bull sperm head measurements and post-thaw non-return to oestrus rates.

Flow cytometric assessment of changes in rat sperm mitochondrial function after treatment with pentachlorophenol.

The fluorophore 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl carbocyanine iodide (JC-1) localizes to the mitochondria and is affected by membrane potential, fluorescing bright orange when the membrane potential is high and green when mitochondrial membrane potential is low. The present study used flow cytometric analysis of JC-1 staining patterns of large numbers of spermatozoa to detect chemical-induced alterations of sperm mitochondrial membrane potential. Cauda epididymal rat spermatozoa were incubated with pentachlorophenol (PCP; 0.

Activity of angiotensin-converting enzyme (ACE) in reproductive tissues of the stallion and effects of angiotensin II on sperm motility.

A testis-specific isoform of angiotensin-converting enzyme (ACE) has been identified in a number of mammalian species. The purpose of this study was to characterize the activity of ACE in equine spermatozoa, seminal plasma, and testis. Activity of ACE was determined in seminal plasma, ejaculated and epididymal spermatozoa from mature stallions as well as from pre- and postpubertal testis.

Growth hormone or insulin-like growth factor-I extends longevity of equine spermatozoa in vitro.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are both present in blood plasma and IGF-I has been measured in epididymal fluid and seminal plasma. This study was designed to investigate the direct effects of GH or IGF-I on the motility of mature equine spermatozoa in vitro. We compared the effects of one concentration (100 ng/ml) of recombinant bovine GH (rbGH) and recombinant human IGF-I (rhIGF-I) on motility and motion characteristics of equine spermatozoa over a 24 h period.

Effect of antioxidants on preservation of motility,viability and acrosomal integrity of equine spermatozoa during storage at 5 degrees C.

Preservation of liquid semen at 5 degrees C is an important technique in the breeding management of horses. Oxidative damage to spermatozoa during storage is a potential cause of the decline in motility and fertility during hypothermic storage of liquid semen. The objective of this study was to evaluate the use of water-soluble and lipid-soluble antioxidants to improve the maintenance of motility of equine spermatozoa at 5 degrees C during storage for 72 to 96 h.

Seminal plasma addition attenuates the dilution effect in bovine sperm.

Dilution of semen to low cell numbers/dose can result in a bull-dependent reduction in the post-thaw viability of cryopreserved bovine spermatozoa. It is possible that essential seminal plasma components are lacking at the greater dilution rates, thereby contributing to the deleterious effects of semen dilution. Ejaculates of 6 Holstein bulls were diluted to 120 x 10(6) sperm/mL in an egg yolk citrate extender (EYC).

Fluorescent probes and flow cytometry to assess rat sperm integrity and mitochondrial function.

Fluorescent assessment of cellular integrity and mitochondrial function by flow cytometry can provide a rapid and precise means of determining the functional status of large numbers of spermatozoa. In the present study, rat sperm viability was assessed with SYBR-14 and PI and sperm mitochondria were differentially labeled with JC-1. Sperm samples of variable viability were prepared using varying proportions of fresh and frozen spermatozoa.

The effect of reactive oxygen species on equine sperm motility, viability, acrosomal integrity, mitochondrial membrane potential, and membrane lipid peroxidation.

The objective of this study was to examine the influence of reactive oxygen species (ROS), generated through the use of the xanthine (X)-xanthine oxidase (XO) system, on equine sperm motility, viability, acrosomal integrity, mitochondrial membrane potential, and membrane lipid peroxidation. Equine spermatozoa were separated from seminal plasma on a discontinuous Percoll gradient, and spermatozoa were incubated with 0.6 mM X and 0.

Catalase activity in equine semen.

Objective: To characterize the activity of catalase in equine semen.

Animals: 15 stallions of known and unknown reproductive history.

Procedure: Seminal plasma was collected from raw equine semen by centrifugation, and samples of seminal plasma were frozen prior to assay for catalase activity.

Assessment of equine sperm mitochondrial function using JC-1.

The fluorescent carbocyanine dye, JC-1, labels mitochondria with high membrane potential orange and mitochondria with low membrane potential green. Evaluation of mitochondrial membrane potential with JC-1 has been used in a variety of cell types, including bull spermatozoa; however, JC-1 staining has not yet been reported for equine spermatozoa. The aim of this study was to apply JC-1 staining and assessment by flow cytometry or a fluorescence microplate reader for evaluation of mitochondrial function of equine spermatozoa.

Computer-assisted sperm head morphometry analysis (ASMA) of cryopreserved ram spermatozoa.

Normal sperm morphology has been shown to be indicative of male fertility; however, subjective methods of assessing morphology are highly variable. Computer-assisted sperm morphometry analysis (ASMA) has been developed for the objective analysis of sperm head dimensions. Developing applicable protocols for sperm head morphometry analysis increases the efficiency of these systems.

IGF-I treatment increases motility and improves morphology of immature spermatozoa in the GH-deficient dwarf (dw/dw) rat.

It has recently been shown that short-term growth hormone (GH) treatment can increase the motility of spermatozoa in the GH-deficient dw/dw rat. To examine whether the effects of GH on motility of immature spermatozoa are mediated by an increase in plasma concentrations of IGF-I, we treated GH-deficient dw/dw rats with 2 microg/g/day of IGF-I using osmotic minipumps. Body weight (saline 227+/-5 g, IGF-I 253+/-4 g) and IGF-I concentrations in blood plasma (saline 472+/-19.

Replicate and technician variation associated with computer aided bull sperm head morphometry analysis (ASMA).

Associations of abnormal spermatozoa with bull fertility have yielded varying results. Manual methods of analysis are subjective and highly variable within and between technicians, which may account for these differences. Computer-aided sperm head morphometry appears to be a precise method of assessing sperm head dimensions; however, the effects of replication and technician on sperm head morphometry have not been assessed.

Effects of cryopreservation on bull sperm head morphometry.

Artificial insemination using cryopreserved semen is a common management tool of the contemporary livestock producer. However, cryopreservation is detrimental to sperm function and fertility, killing some 50% of the spermatozoa during the process. Prediction of cryopreservation damage from prefreeze samples remains elusive.

Percentage of normal sperm heads is significantly increased by Percoll separation of semen.

The purpose of this study was to assess objectively the effects of Percoll separation on human sperm head morphometry. Semen samples were washed and smears were prepared on slides. An aliquot of each sample was centrifuged on a Percoll gradient and spermatozoa were prepared on slides.

Impaired sperm characteristics in postpubertal growth-hormone-deficient dwarf (dw/dw) rats.

The objective of the current study was to determine if sperm function is compromised in rats deficient in growth hormone (dw/dw) since a deficiency in this hormone has been implicated as a cause of lowered fertility and spermatogenic cessation in some biological models. Spermatozoa were recovered from the cauda epididymides of adult dwarf and Wistar control male rats. Spermatozoa were diluted in Medium 199 and analysed for motility.

The effects of cryopreservation on the morphometric dimensions of caprine sperm heads.

Cryopreserved semen has been utilised in the artificial insemination of livestock species for over 40 years, even though the detrimental effects of cryopreservation on sperm function and fertility are well documented. In the present study, computer-automated sperm-head morphometry was used to determine if goat sperm-head morphometry was affected by freezing and thawing. A microscope slide was prepared from single semen samples, collected by artificial vagina, from 10 sexually active Saanen bucks.

Sperm head morphometry analysis of ejaculate and dismount stallion semen samples.

The evaluation of seminal characteristics is important in the clinical detection of stallion subfertility. Conventional semen evaluation includes subjective determination of sperm concentration, motility, and gross morphology. Due to the subjectivity and variability of the manual morphology assessment, computer automated sperm morphology analyses has been developed.

Morphometric differences in sperm head dimensions of fertile and subfertile stallions.

Gross morphological evaluation of stallion spermatozoa is of clinical value in assessing male fertility in the horse. While of value, methods of subjective sperm classification yield highly variable results. Recent development of computer-assisted sperm morphometry analysis (ASMA) technology has allowed for the objective analysis of sperm head morphometry.

Quantification of normal head morphometry of stallion spermatozoa.

The heads of stallion spermatozoa were analysed by computer automated sperm head morphometry and the morphometric values of the major subpopulations of sperm heads were assessed. The criteria for normal dimensions of stallion sperm heads are proposed based on the analysis of these measurements. Semen samples were collected from 10 fertile and 10 subfertile stallions, processed by a standard method, smeared onto microscope slides and stained using haematoxylin.

Growth hormone (GH) therapy markedly increases the motility of spermatozoa and the concentration of insulin-like growth factor-I in seminal vesicle fluid in the male GH-deficient dwarf rat.

There is increasing evidence for an important role of the somatotropic axis in male reproductive function. We investigated the effect of recombinant bovine GH (rbGH) treatment for 21 days on semen characteristics in post-pubertal GH-deficient dwarf (dw/dw) rats. Male dw/dw rats at an age of 75-80 days were divided into two groups (n = 10 per group) and injected twice per day with either rbGH (2 micrograms/g/day) or saline.