Exposure of rat colonic mucosa to human semen in vivo induces mucosal cytolysis, abolishes fluid absorption and raises paracellular permeability

1992 ◽  
Vol 82 (3) ◽  
pp. 277-282 ◽  
Author(s):  
M. V. Mendizabal ◽  
R. J. Naftalin
Keyword(s):  
Polyethylene Glycol ◽  
Seminal Plasma ◽  
Colonic Mucosa ◽  
Human Semen ◽  
Fluid Absorption ◽  
Colonic Wall ◽  
Polyethylene Glycol 4000 ◽  
Bacterial Collagenase ◽  
Colonic Lumen

1. The effects of human semen on rat descending colon fluid absorption, permeability to 3H-labelled polyethylene glycol 4000 and the histological appearance of the mucosa were examined. Also, the semen was fractioned by centrifugation into plasma and sperm fractions and the effects of these fractions on rat colonic function were examined. The effects of trypsin and bacterial collagenase, mimetics of acrosin and seminal collagenase activity, were examined in order to investigate which component of human semen alters colonic permeability. 2. Contact between human semen and rat descending colonic mucosa for 3 h decreased fluid absorption from 52.0 ± 2.9 μl h−1 cm−2 (control) to 10.7 ± 3.4 μl h−1 cm−2 (P >0.001), increased the permeability to polyethylene glycol 4000 from 0.099 ± 0.006 cm/h (control) to 0.31 ± 0.04 cm/h (P>0.001) and caused cytolysis of the surface mucosa. 3. Spermatazoa inside the colonic lumen were destroyed within 1 h with release of acrosomal contents; this raised the activity of the acrosomal proteolytic enzyme acrosin by 40-fold (P >0.005) and of seminal plasma metalloproteinase (collagenase) by about twofold (mean activity 1623 ± 240 units/ml of luminal fluid). 4. The changes in colonic permeability induced by seminal plasma were similar to those induced by similar activities of clostridial collagenase. 5. We conclude that seminal collagenase is present in sufficient amounts to cause acute damage to the colonic mucosa, and that this could be a factor in facilitating viral transmission across the colonic wall.

Effects of spermine on water absorption, polyethylene glycol 4000 permeability and collagenase activity in rat descending colon in vivo

1992 ◽  
Vol 83 (4) ◽  
pp. 417-423 ◽  
Author(s):  
M. V. Mendizabal ◽  
R. J. Naftalin
Keyword(s):  
Polyethylene Glycol ◽  
Dependent Manner ◽  
Fluid Absorption ◽  
Collagenase Activity ◽  
Oedema Formation ◽  
Polyethylene Glycol 4000 ◽  
Control Value ◽  
Anionic Charge ◽  
Descending Colon

1. The effects of spermine in the concentration range 0–10 mmol/l on (a) the fluid absorption, (b) the polyethylene glycol permeability, (c) the release of collagenase activity activity into the lumen and (d) the histological appearance of rat descending colon were examined. 2. Spermine (5 mmol/l) decreased fluid absorption from 48.83 ± 2.98 (n = 7) to 23.98 ± 2.32 (n = 6) μl h−1 cm−2 (P<0.01); polyethylene glycol 4000 permeability was increased from 0.030 ± 0.001 (n = 7) to 0.047 ± 0.003 (n = 6) cm/h (P<0.01) and luminal collagenase activity increased from a negligible control value to 250 ± 39 (n = 6) units/ml (P<0.001). Spermine also caused oedema formation within the mucosal interstitial fluid, without inducing an overt breakdown of the mucosa at the luminal surface. 3. Polyamine-free dialysed seminal plasma had no effect on polyethylene glycol 4000 permeability, although it still caused a significant decrease in colonic fluid absorption from 48.83 ± 2.98 (n = 7) (control) to 31.41 ± 2.08 (n = 5) μl h−1 cm−2 (P<0.01). 4. Low-molecular-mass heparin (600 units/ml) prevented the spermine (5 mmol/l)- and whole-semen-induced increase in colonic polyethylene glycol 4000 permeability and reduced the effect of semen on fluid absorption by 63% (P<0.001) and that of spermine by 56% (P<0.01). 5. The Zn2+ chelator and collagenase inhibitor o-phenanthroline reduced the effect of spermine on fluid absorption and polyethylene glycol 4000 permeability by 100% (P<0.001) and on interstitial oedema formation. o-Phenanthroline also reduced the effects of whole semen on fluid absorption (by 70%, P<0.01) and on polyethylene glycol 4000 permeability by 95%, P<0.01). 6. A synthetic peptide inhibitor of mammalian collagenase activity with high affinity reduced the effects of whole semen on polyethylene glycol 4000 permeability (P<0.01) and on fluid absorption (P<0.01) in a dose-dependent manner. The inhibitor (2 mmol/l) also reduced the effects of spermine (5 mmol/l) on fluid absorption and polyethylene glycol 4000 permeability. 7. These results indicate that polyamines that are present within semen in the concentration range 5–15 mmol/l act co-operatively with seminal collagenases to disrupt the colonic barrier. Cationic polyamines may activate collagenases by binding to and neutralizing the anionic charge of heparins within the interstitial matrix.

Physicochemical characterization and in vivo properties of Zolpidem in solid dispersions with polyethylene glycol 4000 and 6000

1999 ◽  
Vol 184 (1) ◽  
pp. 121-130 ◽  
Author(s):  
Giuseppe Trapani ◽  
Massimo Franco ◽  
Andrea Latrofa ◽  
Maria Rosaria Pantaleo ◽  
Maria Rosaria Provenzano ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Solid Dispersions ◽  
Physicochemical Characterization ◽  
Polyethylene Glycol 4000

A novel colon-specific steroid prodrug enhances sodium chloride absorption in rat colitis

1995 ◽  
Vol 269 (2) ◽  
pp. G210-G218
Author(s):  
R. N. Fedorak ◽  
N. Cui ◽  
D. R. Friend ◽  
K. L. Madsen ◽  
L. R. Empey
Keyword(s):  
Sodium Chloride ◽  
Colonic Mucosa ◽  
Epithelial Transport ◽  
Free Drug ◽  
Fluid Absorption ◽  
Ussing Chambers ◽  
Mucosal Integrity ◽  
Chloride Absorption

A recently synthesized novel colon-specific dexamethasone prodrug, dexamethasone-beta-D-glucuronide, delivers efficacious amounts of dexamethasone to the colon with limited adrenal suppressive effects. During experimentally induced colitis in rats, the dexamethasone prodrug is significantly more potent than free dexamethasone in improving colonic fluid and electrolyte absorptive injury. The present studies examined whether the improvement in colonic absorption seen with the prodrug occurred as a consequence of alterations in sodium and chloride epithelial transport. The efficacy of the dexamethasone prodrug and free dexamethasone were tested in an acetic acid-induced rat model of colitis. Healing of the induced colitis was assessed by measuring net colonic fluid absorption and surface area ulceration. Transmural unidirectional fluxes of 22Na and 36Cl across sheets of colonic mucosa were measured in Ussing chambers. Treatment of colitis with the prodrug delivered a sixfold higher concentration of dexamethasone to the colon than did treatment with the free drug. The prodrug accelerated healing of colitis by returning in vivo colonic fluid absorption to normal and virtually eliminated colonic macroscopic ulceration, whereas the free drug did not. In vitro transmural fluxes demonstrated that, in addition to repair of mucosal integrity, the prodrug enhanced electroneutral sodium chloride absorption over and above that seen in control animals or after treatment with the free drug. Both the prodrug and the free drug limited theophylline-mediated net chloride and sodium secretion, an effect that would be consistent with the antidiarrheal effect induced by these drugs in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

A polyethylene glycol based medium for in vitro germination of cashew pollen

1984 ◽  
Vol 62 (12) ◽  
pp. 2473-2475 ◽  
Author(s):  
C. C. Subbaiah
Keyword(s):  
Polyethylene Glycol ◽  
Pollen Tubes ◽  
Anacardium Occidentale ◽  
In Vitro Germination ◽  
Inorganic Elements ◽  
Polyethylene Glycol 4000 ◽  
Germination Of Pollen

A medium, comprising polyethylene glycol 4000, sucrose, boron, and calcium, for in vitro germination of pollen in cashew (Anacardium occidentale L.) gave 90–95% germination as well as excellent pollen tubes comparable with those found in vivo. The better performance of this combination compared with media containing only sucrose and inorganic elements is discussed in relation to the superiority of polyethylene glycol to sucrose as an osmoticum.

scholarly journals Oxidation of polymines by diamine oxidase from human seminal plasma

1975 ◽  
Vol 145 (2) ◽  
pp. 373-378 ◽  
Author(s):  
E Hölttä ◽  
P Pulkkinen ◽  
K Elfving ◽  
J Jänne
Keyword(s):  
Molecular Weight ◽  
Seminal Plasma ◽  
Gel Electrophoresis ◽  
Diamine Oxidase ◽  
Polyacrylamide Gel Electrophoresis ◽  
Polyacrylamide Gel ◽  
Human Semen ◽  
Human Seminal Plasma ◽  
Ph Values

1. Diamine oxidase [amine-oxygen oxidoreductase (deaminating)(pyridoxal-containing), EC 1.4.3.6] was purified from human seminal plasma more than 1,700-fold. The enzyme appeared to be homogeneous on polyacrylamide-gel electrophoresis at two different pH values. 2. The general properties of the enzyme were comparable with those described for other diamine oxidases from different mammalian sources. The molecular weight of the enzyme was calculated to be about 182,000. 3. The enzyme had highest affinity for diamines, but polyamines spermidine and spermine were also degraded at concentrations that can be considered physiological in human semen. 3. The possible degradation of spermine by diamine oxidase in human semen in vivo may give rise to the formation of cytotoxic aldehydes that conceivably can influence the motility and survival of the spermatozoa.

Co-delivery of Doxorubicin and D-α-Tocopherol Polyethylene Glycol 1000 Succinate by Magnetic Nanoparticles

2018 ◽  
Vol 18 (8) ◽  
pp. 1138-1147 ◽  
Author(s):  
Esra Metin ◽  
Pelin Mutlu ◽  
Ufuk Gündüz
Keyword(s):  
Breast Cancer ◽  
Polyethylene Glycol ◽  
Magnetic Nanoparticles ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Drug Loading ◽  
Gravimetric Analysis ◽  
Polyethylene Glycol 1000 ◽  
Mcf 7

Background: Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells are also affected, just like cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks. Objective: The aim of this study was targeted co-delivery of doxorubicin (Dox) which is an anticancer agent and D-α-Tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) to breast cancer cells. For this purpose, Magnetic Nanoparticles (MNPs) were synthesized and coated with Oleic Acid (OA). Coated nanoparticles were encapsulated in Poly Lactic-co-Glycolic Acid (PLGA) and TPGS polymers and loaded with Dox. The Nanoparticles (NPs) were characterized by Fourier Transform Infrared (FTIR) spectroscopy, zetapotential analysis, Dynamic Light Scattering (DLS) analysis, Thermal Gravimetric Analysis (TGA) and Scanning Electron Microscope (SEM) analysis. Results: The results showed that NPs were spherical, superparamagnetic and in the desired range for use in drug targeting. The targetability of NPs was confirmed. Moreover, TPGS and Dox loading was shown by TGA and FTIR analyses. NPs were internalized by cells and the cytotoxic effect of drug loaded NPs on sensitive (MCF-7) and drug-resistant (MCF-7/Dox) cells were examined. It was seen that the presence of TPGS increased cytotoxicity significantly. TPGS also enhanced drug loading efficiency, release rate, cellular internalization. In MCF- 7/Dox cells, the drug resistance seems to be decreased when Dox is loaded onto TPGS containing NPs. Conclusion: This magnetic PLGA nanoparticle system is important for new generation targeted chemotherapy and could be used for breast cancer treatment after in vivo tests.

scholarly journals Seminal Plasma: Relevant for Fertility?

2021 ◽  
Vol 22 (9) ◽  
pp. 4368
Author(s):  
Heriberto Rodriguez-Martinez ◽  
Emilio A. Martinez ◽  
Juan J. Calvete ◽  
Fernando J. Peña Vega ◽  
Jordi Roca
Keyword(s):  
Seminal Plasma ◽  
Current Knowledge ◽  
Inorganic Ions ◽  
Vitro Fertilization ◽  
Dna And Rna ◽  
Model Animal ◽  
Sexual Glands ◽  
Species Specific

Seminal plasma (SP), the non-cellular component of semen, is a heterogeneous composite fluid built by secretions of the testis, the epididymis and the accessory sexual glands. Its composition, despite species-specific anatomical peculiarities, consistently contains inorganic ions, specific hormones, proteins and peptides, including cytokines and enzymes, cholesterol, DNA and RNA—the latter often protected within epididymis- or prostate-derived extracellular vesicles. It is beyond question that the SP participates in diverse aspects of sperm function pre-fertilization events. The SP also interacts with the various compartments of the tubular genital tract, triggering changes in gene function that prepares for an eventual successful pregnancy; thus, it ultimately modulates fertility. Despite these concepts, it is imperative to remember that SP-free spermatozoa (epididymal or washed ejaculated) are still fertile, so this review shall focus on the differences between the in vivo roles of the SP following semen deposition in the female and those regarding additions of SP on spermatozoa handled for artificial reproduction, including cryopreservation, from artificial insemination to in vitro fertilization. This review attempts, including our own results on model animal species, to critically summarize the current knowledge of the reproductive roles played by SP components, particularly in our own species, which is increasingly affected by infertility. The ultimate goal is to reconcile the delicate balance between the SP molecular concentration and their concerted effects after temporal exposure in vivo. We aim to appraise the functions of the SP components, their relevance as diagnostic biomarkers and their value as eventual additives to refine reproductive strategies, including biotechnologies, in livestock models and humans.

scholarly journals Surrogate post-coital testing for contraceptive efficacy against human sperm activity in the ovine vaginal model†

2020 ◽  
Author(s):  
Yong Zhu ◽  
Jamal Saada ◽  
Shrestha Bhawana ◽  
Sam Lai ◽  
Paula Villarreal ◽  
...  
Keyword(s):  
Human Sperm ◽  
Vaginal Fluid ◽  
Human Semen ◽  
Ovine Model ◽  
Igg Antibody ◽  
Study Objective ◽  
In Vivo Testing ◽  
Efficacy Assessment ◽  
Sperm Immobilization

Abstract High unintended pregnancy rates are partially due to lack of effective nonhormonal contraceptives; development of safe, effective topical vaginal methods will address this need. Preclinical product safety and efficacy assessment requires in vivo testing in appropriate models. The sheep is a good model for the evaluation of vaginally delivered products due to its close similarities to humans. The study objective was to develop an ovine model for efficacy testing of female nonhormonal contraceptives that target human sperm. Fresh human semen was pooled from male volunteers. Nonpregnant female Merino sheep were treated with control or vaginal contraceptive product (IgG antibody with action against sperm or nonoxynol-9 [N9]). Pooled semen was added to the sheep vagina and mixed with product and vaginal secretions. Microscopic assessment of samples was performed immediately and progressive motility (PM) of sperm was compared between treatments. Cytokines CXCL8 and IL1B were assessed in vaginal fluid after instillation of human semen. No adverse reactions or elevations in proinflammatory cytokines occurred in response to human semen. N9 produced signs of acute cellular toxicity while there were no cellular changes after IgG treatment. N9 and IgG had dose-related effects with the highest dose achieving complete sperm immobilization (no sperm with PM). Surrogate post-coital testing of vaginally administered contraceptives that target human semen was developed in an ovine model established for vaginal product preclinical testing. This expanded model can aid the development of much needed nonhormonal topical vaginal contraceptives, providing opportunities for rapid iterative drug development prior to costly, time-intensive human testing.

scholarly journals Specific Seminal Plasma Fractions Are Responsible for the Modulation of Sperm–PMN Binding in the Donkey

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1388
Author(s):  
Jordi Miró ◽  
Jaime Catalán ◽  
Henar Marín ◽  
Iván Yánez-Ortiz ◽  
Marc Yeste
Keyword(s):  
Molecular Weight ◽  
Sperm Motility ◽  
Seminal Plasma ◽  
Potential Effect ◽  
Polymorphonuclear Neutrophils ◽  
Low Fertility ◽  
Plasma Fractions ◽  
Complex Fluid ◽  
First Time

While artificial insemination (AI) with frozen-thawed sperm results in low fertility rates in donkeys, the addition of seminal plasma, removed during cryopreservation, partially counteracts that reduction. Related to this, an apparent inflammatory reaction in jennies is induced following AI with frozen-thawed sperm, as a high amount of polymorphonuclear neutrophils (PMN) are observed within the donkey uterus six hours after AI. While PMN appear to select the sperm that ultimately reach the oviduct, two mechanisms, phagocytosis and NETosis, have been purported to be involved in that clearance. Remarkably, sperm interacts with PMN, but the presence of seminal plasma reduces that binding. As seminal plasma is a complex fluid made up of different molecules, including proteins, this study aimed to evaluate how different seminal plasma fractions, separated by molecular weight (<3, 3–10, 10–30, 30–50, 50–100, and >100 kDa), affect sperm–PMN binding. Sperm motility, viability, and sperm–PMN binding were evaluated after 0 h, 1 h, 2 h, 3 h, and 4 h of co-incubation at 38 °C. Two seminal plasma fractions, including 30–50 kDa or 50–100 kDa proteins, showed the highest sperm motility and viability. As viability of sperm not bound to PMN after 3 h of incubation was the highest in the presence of 30–50 and 50–100 kDa proteins, we suggest that both fractions are involved in the control of the jenny’s post-breeding inflammatory response. In conclusion, this study has shown for the first time that specific fractions rather than the entire seminal plasma modulate sperm–PMN binding within the donkey uterus. As several proteins suggested to be involved in the control of post-AI endometritis have a molecular weight between 30 and 100 kDa, further studies aimed at determining the identity of these molecules and evaluating their potential effect in vivo are much warranted.

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