Contents
Paraoxonase‐1 (PON1) is an enzyme found in serum and follicular fluid that protects cell membrane and circulating lipids against oxidative damage. The aims of this study were to measure the ...direct effects of recombinant PON1 (rPON1) on bovine oocyte maturation at the molecular level (gene expression) and to measure the carry‐over effects of PON1 on pre‐implantation embryo development in vitro. COCs were submitted to IVM with the addition of 0.0, 0.02, 0.04 and 0.08 mg ml−1 of rPON1, corresponding to an average PON1 arylesterase enzyme activity of 2.2 ± 0.4, 15.5 ± 1.5, 30.2 ± 3.0 and 57.9 ± 5.0 U ml−1, respectively. The results indicated that addition of rPON1 during IVM improved embryo development in a dose‐dependent manner as D7 embryo development was 22.2%, 29.4%, 32.2% and 37.0% for the treatment groups, respectively (p = 0.02). In conclusion, addition of PON1 enzyme during IVM exerted dose‐related positive effects on embryo development rates to blastocysts.
Contents
Normal metabolic activity in ovarian follicles may result in oxidative stress and damage to oocytes. The aim of this study was to evaluate expression of the natural anti‐oxidants paraoxonase ...(PON) 1, 2 and 3 in granulosa cells and PON1 activity in follicular fluid (FF) and plasma of dairy cows. For the first experiment, ovaries were collected from cows at slaughter, after which follicles were dissected and classified as oestrogen active (EAF) or atretic (ATF). Expression of PON1, PON2 and PON3 mRNA was evaluated in granulosa cells, and activity of PON1 was measured in FF. PON1 mRNA was undetectable in granulosa cells, PON2 mRNA expression was not different between follicle types, and PON3 mRNA tended to be higher in EAF (p = 0.11). The activity of PON1 in FF was higher (p = 0.01) for EAF (82.6 ± 8.0 kU/L) than ATF (53.9 ± 6.8 kU/L), as were high‐density lipoproteins (HDL), low‐density lipoproteins (LDL) and total cholesterol concentrations. In the second experiment, we aimed to compare plasma and FF PON1 activity in early lactation Holstein cows (n = 15) with pre‐ovulatory EAF. Activity of PON1 was twofold higher (p < 0.0001) in plasma (122.5 ± 11.1 kU/L) than in FF (61.4 ± 5.2 kU/L). Plasma concentrations were also higher (p < 0.0001) for HDL, LDL and total cholesterol when compared to FF. In conclusion, FF concentrations of PON1, HDL, LDL and total cholesterol were higher in healthy oestrogen active bovine follicles than in atretic follicles. PON1 was not expressed by granulosa cells indicating that high PON1 activity in bovine FF is apparently derived by transfer from blood in association with HDL.
Amniocentesis is a routine procedure utilized on several species including human, equine, and bovine patients. Early assessment and discovery of new genetic traits in the cattle industry are highly ...desirable in order to accelerate genetic gain by shortening generational intervals. One of the main concerns from this procedure is the introduction of pathogenic bacterial contamination into the amniotic cavity thereby increasing the risks of spontaneous pregnancy losses post procedure. In this randomized controlled equivalence study, we have tested the effect of antimicrobial prophylaxis on the incidence of spontaneous abortions and contrasted it to untreated individuals post amniocentesis. On the treated group (n = 67) all heifers remained pregnant whereas 1 of the untreated group (n = 65) resulted in a spontaneous abortion during the study period. The latter represents 1.54% of pregnancy losses attributed to the risk associated to the amniocentesis procedure. However, the probability of inducing spontaneous abortion from the technique itself is not different to that of the contemporaneous population (n = 694) not undergoing amniocentesis viz., 1.59%. Following a two-tailed distribution, statistical analyses showed no significant differences across treatments (Fisher's exact test P = 0.49). The current prospective study indicates that performing amniocenteses on cattle have resulted in similar spontaneous pregnancy losses comparable to those of pregnant heifers without undergoing amniocentesis and regardless of antimicrobial use. In conclusion, prophylactic antimicrobials may not be applicable within the cattle amniocentesis framework.
Objectives
Searching for more effective and selective therapies for head and neck cancer, we demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) to treat oral cancer and ...inhibit long‐term tumor development from field‐cancerized tissue in the hamster cheek pouch model. However, BNCT‐induced mucositis in field‐cancerized tissue was dose limiting. In a clinical scenario, oral mucositis affects patients’ treatment and quality of life. Our aim was to evaluate different radioprotectors, seeking to reduce the incidence of BNCT‐induced severe mucositis in field‐cancerized tissue.
Materials and Methods
Cancerized pouches treated with BNCT mediated by boronophenylalanine at 5 Gy were treated as follows: control: saline solution; Hishigh: histamine 5 mg kg−1; Hislow: histamine 1 mg kg−1; and JNJ7777120: 10 mg kg−1.
Results
Hislow reduced the incidence of severe mucositis in field‐cancerized tissue to 17% vs CONTROL: 55%; Hishigh: 67%; JNJ7777120: 57%. Hislow was non‐toxic and did not compromise the long‐term therapeutic effect of BNCT or alter gross boron concentration. Conclusion: Histamine reduces BNCT‐induced mucositis in experimental oral precancer without jeopardizing therapeutic efficacy. The fact that both histamine and boronophenylalanine are approved for use in humans bridges the gap between experimental work and potential clinical application to reduce BNCT‐induced radiotoxicity in patients with head and neck cancer.
Objective
The objective of this study was to investigate whether histamine H4 receptor (H4R) antagonists could prevent experimental periodontitis (EP)‐induced histological, functional and ...inflammatory alterations in submandibular gland (SMG), periodontal bone and gingiva.
Methods
Bilateral EP was induced for 2 weeks in anaesthetized male rats. The effect of systemic and local administration of H4R antagonists (JNJ7777120, JNJ10191584) on histopathology and functionality of SMG, bone loss and gingival inflammation was evaluated.
Results
The subcutaneous administration of JNJ7777120 prevented periodontitis‐induced SMG histological injury, reducing vacuolization and apoptosis and additionally reversed the increased prostaglandin E2 (PGE2) levels in SMG while it partially reversed the methacholine‐induced salivation reduction produced by periodontitis. JNJ7777120 attenuated bone loss and the increased PGE2 levels and inflammatory infiltration in gingival tissue of rats with periodontitis. Finally, local administration of JNJ7777120 and JNJ10191584 was also beneficial for improving periodontal parameters.
Conclusions
H4 receptor antagonists are able to ameliorate periodontitis‐induced injury on SMG, gingival tissue and bone structure, suggesting that pharmacological targeting of H4R could be an attractive strategy to improve periodontal health.
The exposure to high doses of ionizing radiation during radiotherapy results in severe morphological and functional alterations of the salivary glands, such as xerostomia. In the present study we ...investigated the chronic effect of a single radiation dose of 15 Gray (Gy) limited to head and neck on rat salivary gland function (salivary secretion and gland mass) and histology. Results indicate that norepinephrine (NE)-induced salivary secretion was reduced significantly at 30, 90, 180 and 365 days after the administration of a single dose of 15 Gy of ionizing radiation compared to non-irradiated animals. The maximal secretory response was reduced by 33% at 30 and 90 days post irradiation. Interestingly, a new fall in the salivary response to NE was observed at 180 days and was maintained at 365 days post irradiation, showing a 75% reduction in the maximal response. The functional fall of the salivary secretion observed at 180 days post irradiation was not only associated with a reduction of gland mass but also to an alteration of the epithelial architecture exhibiting a changed proportion of ducts and acini, loss of eosinophilic secretor granular material, and glandular vacuolization and fibrosis. On the basis of the presented results, we conclude that ionizing radiation produces irreversible and progressive alterations of submandibular gland (SMG) function and morphology that leads to a severe salivary hypo-function.
The present study examined pacing site-dependent changes in QT interval and transmural dispersion of repolarization (TDR) and their potential role in the development of torsade de pointes (TdP).
In ...humans, the QT interval, JT interval, and TDR were measured in 29 patients with heart failure during right ventricular endocardial pacing (RVEndoP), biventricular pacing (BiVP), and left ventricular epicardial pacing (LVEpiP). In animal experiments, pacing site--dependent changes in ventricular repolarization were examined with a rabbit left ventricular wedge preparation in which action potentials from endocardium and epicardium could be simultaneously recorded with a transmural ECG. In humans, LVEpiP and BiVP led to significant QT and JT prolongation. LVEpiP also enhanced TDR. Frequent R-on-T extrasystoles generated by BiVP and LVEpiP but completely inhibited by RVEndoP occurred in 4 patients, of whom 1 developed multiple episodes of nonsustained polymorphic ventricular tachycardia and another suffered incessant TdP. In rabbit experiments, switching from endocardial to epicardial pacing produced a net increase in QT interval and TDR by 17+/-5 and 22+/-5 ms, respectively (n=6, P<0.01), without parallel increases in ventricular transmembrane action potential durations. Epicardial pacing facilitated transmural propagation of early afterdepolarization, leading to the development of R-on-T extrasystoles and TdP in the presence of action potential duration-prolonging agents.
LVEpiP and BiVP increase QT, JT, and TDR by altering the transmural sequence of activation of the intrinsically heterogeneous ventricular myocardium. Our data suggest that the resultant exaggeration of arrhythmic substrates can lead to the development of TdP in a subset of patients.
The aim of the present work was to evaluate the potential protective effect of histamine on Doxorubicin (Dox)-induced hepatic and cardiac toxicity in different rodent species and in a triple-negative ...breast tumor-bearing mice model. Male Sprague Dawley rats and Balb/c mice were divided into four groups: control (received saline), histamine (5 mg/kg for rats and 1 mg/kg for mice, daily subcutaneous injection starting 24 h before treatment with Dox), Dox (2 mg/kg, intraperitoneally injected three times a week for 2 weeks) and Dox+histamine (received both treatments). Tissue toxicity was evaluated by histopathological studies and oxidative stress and biochemical parameters. The combined effect of histamine and Dox was also investigated in vitro and in vivo in human MDA-MB-231 triple-negative breast cancer model. Heart and liver of Dox-treated animals displayed severe histological damage, loss of tissue weight, increased TBARS levels and DNA damage along with an augment in serum creatine kinase-myocardial band. Pretreatment with histamine prevented Dox-induced tissue events producing a significant preservation of the integrity of both rat and mouse myocardium and liver, through the reduction of Dox-induced oxidative stress and apoptosis. Histamine treatment preserved anti-tumor activity of Dox, exhibiting differential cytotoxicity and increasing the Dox-induced inhibition of breast tumor growth. Findings provide preclinical evidence indicating that histamine could be a promising candidate as a selective cytoprotective agent for the treatment of Dox-induced cardiac and hepatic toxicity, and encourage the translation to clinical practice.
Objective
The objective of this study was to investigate whether histamine H
4
receptor (H
4
R) antagonists could prevent experimental periodontitis (
EP
)‐induced histological, functional and ...inflammatory alterations in submandibular gland (
SMG
), periodontal bone and gingiva.
Methods
Bilateral
EP
was induced for 2 weeks in anaesthetized male rats. The effect of systemic and local administration of H
4
R antagonists (
JNJ
7777120,
JNJ
10191584) on histopathology and functionality of
SMG
, bone loss and gingival inflammation was evaluated.
Results
The subcutaneous administration of
JNJ
7777120 prevented periodontitis‐induced
SMG
histological injury, reducing vacuolization and apoptosis and additionally reversed the increased prostaglandin E2 (PGE2) levels in
SMG
while it partially reversed the methacholine‐induced salivation reduction produced by periodontitis.
JNJ
7777120 attenuated bone loss and the increased
PGE
2 levels and inflammatory infiltration in gingival tissue of rats with periodontitis. Finally, local administration of
JNJ
7777120 and
JNJ
10191584 was also beneficial for improving periodontal parameters.
Conclusions
H
4
receptor antagonists are able to ameliorate periodontitis‐induced injury on
SMG
, gingival tissue and bone structure, suggesting that pharmacological targeting of H
4
R could be an attractive strategy to improve periodontal health.
Contents
Normal metabolic activity in ovarian follicles may result in oxidative stress and damage to oocytes. The aim of this study was to evaluate expression of the natural anti‐oxidants paraoxonase ...(
PON
) 1, 2 and 3 in granulosa cells and
PON
1 activity in follicular fluid (
FF
) and plasma of dairy cows. For the first experiment, ovaries were collected from cows at slaughter, after which follicles were dissected and classified as oestrogen active (
EAF
) or atretic (
ATF
). Expression of
PON
1,
PON
2 and
PON
3 m
RNA
was evaluated in granulosa cells, and activity of
PON
1 was measured in
FF
.
PON
1 m
RNA
was undetectable in granulosa cells,
PON
2 m
RNA
expression was not different between follicle types, and
PON
3 m
RNA
tended to be higher in
EAF
(p = 0.11). The activity of
PON
1 in
FF
was higher (p = 0.01) for
EAF
(82.6 ± 8.0 k
U
/
L
) than
ATF
(53.9 ± 6.8 k
U
/
L
), as were high‐density lipoproteins (
HDL
), low‐density lipoproteins (
LDL
) and total cholesterol concentrations. In the second experiment, we aimed to compare plasma and
FF PON
1 activity in early lactation
H
olstein cows (n = 15) with pre‐ovulatory
EAF
. Activity of
PON
1 was twofold higher (p < 0.0001) in plasma (122.5 ± 11.1 k
U
/
L
) than in
FF
(61.4 ± 5.2 k
U
/
L
). Plasma concentrations were also higher (p < 0.0001) for
HDL
,
LDL
and total cholesterol when compared to
FF
. In conclusion,
FF
concentrations of
PON
1,
HDL
,
LDL
and total cholesterol were higher in healthy oestrogen active bovine follicles than in atretic follicles.
PON
1 was not expressed by granulosa cells indicating that high
PON
1 activity in bovine
FF
is apparently derived by transfer from blood in association with
HDL
.
PDF
