scholarly journals Neutralization of Relaxin within the Brain Affects the Timing of Birth in Rats*

Endocrinology ◽  
1998 ◽  
Vol 139 (2) ◽  
pp. 479-484 ◽  
Author(s):  
A. J. S. Summerlee ◽  
D. G. Ramsey ◽  
R. S. Poterski
Keyword(s):  
Monoclonal Antibody ◽  
Birth Rate ◽  
Physiological Role ◽  
Live Birth Rate ◽  
Premature Delivery ◽  
Specific Monoclonal Antibody ◽  
Pregnant Rats ◽  
Plasma Progesterone ◽  
The Brain ◽  
Length Of Gestation

Abstract Experiments were performed to determine whether neutralization of relaxin in the brain, by injecting monoclonal antibodies to rat relaxin into the ventricular system of the brain, affected either the timing or the processes of birth in rats. Pregnant rats were injected daily through a chronically implanted intracerebroventricular cannula either with a specific monoclonal antibody raised against rat relaxin from days 12–22 of gestation or with an antibody raised against fluorescein as a control. The rats were watched closely from the afternoon of day 20 of pregnancy, and the process of birth was observed. No sign of dystocia was observed in any of the rats in the experiment. Neutralization of endogenous relaxin caused a significant decrease in the length of gestation (505.4 ± 3.1 h) compared with that in rats treated with PBS (524.6 ± 0.5 h) or that in rats treated with a nonspecific antibody (525.9 ± 0.7 h). The time to the onset of delivery was also shorter in the relaxin-neutralized group (507.8 ± 1.1 h) compared with that in either PBS-treated (526.5 ± 0.6 h) or fluorescein antibody-treated (525.3 ± 0.7 h) animals. In contrast, there was no significant effect of the relaxin antibody on length of straining, duration of parturition, delivery interval, live birth rate, or body weight of the neonates. Premature delivery in the relaxin-neutralized group was accompanied by a 24-h advance in the fall in plasma progesterone. These data support the hypothesis that there may be a central relaxin system that is independent of the peripheral relaxin system. Central relaxin may have a significant physiological role on the timing of pregnancy in the rat, but does not affect the course of labor once it has started.

THE EFFECTS OF DEXAMETHASONE AND INDOMETHACIN ON THE OUTCOME OF PREGNANCY IN THE RABBIT

1975 ◽  
Vol 64 (2) ◽  
pp. 363-370 ◽  
Author(s):  
J. R. G. CHALLIS ◽  
I. J. DAVIES ◽  
K. J. RYAN
Keyword(s):  
Late Pregnancy ◽  
Late Gestation ◽  
Premature Delivery ◽  
Progesterone Concentration ◽  
Dexamethasone Treatment ◽  
Similar Time ◽  
Plasma Progesterone ◽  
Peripheral Plasma ◽  
Prostaglandin F ◽  
Length Of Gestation

SUMMARY Pregnant rabbits were treated with indomethacin (8–10 mg/kg/day) or dexamethasone (1·2–1·8 mg/kg/day) during late gestation. The effects of these treatments on the concentrations of progesterone and prostaglandin F (PGF) in the peripheral plasma, and the outcome of gestation were studied. Treatment with indomethacin significantly prolonged the length of gestation (P < 0·01) compared with control, untreated animals. In these treated animals, the plasma progesterone levels declined at a similar time to that in control rabbits but the increase in systemic PGF normally seen during late pregnancy was reduced. Dexamethasone treatment reliably induced premature delivery within 3–6 days. The plasma progesterone concentration fell rapidly during the first 24 h of dexamethasone administration, but in no animal was this associated with a significant increase in the plasma levels of PGF. These results are consistent with the suggestion that prostaglandins are involved in the normal initiation of parturition in the rabbit. They do not support the hypothesis that the effect of dexamethasone on the length of gestation is mediated through an increase in the production of prostaglandin F.

scholarly journals IDIOPATHIC RECURRENT MISCARRIAGES

2016 ◽  
Vol 23 (09) ◽  
pp. 1033-1038
Author(s):  
Farhat ul Ain Ahmed ◽  
Numeera Faryad
Keyword(s):  
Live Birth ◽  
Birth Rate ◽  
Fetal Death ◽  
Recurrent Miscarriage ◽  
Live Birth Rate ◽  
Secondary Outcome ◽  
Pharmacological Intervention ◽  
Premature Delivery ◽  
Recurrent Miscarriages ◽  
Intensive Surveillance

Objectives: The rationale of our study is to investigate whether aspirin alone,or aspirin combined with low molecular weight heparin as compared to placebo (intensivepregnancy surveillance), would improve the live birth rate (primary outcome) among withidiopathic recurrent miscarriages. Secondary outcomes included rate of serious adverse eventsduring pregnancy among pharmacological intervention group and intensive surveillance group:rates of miscarriage, intrauterine fetal death (fetal death after 24 weeks of gestation), small forgestational age, premature delivery, APH and PPH. Study Design: A prospective, randomized,single-blinded, placebo- controlled trial was conducted at Tertiary Referral Obstetric Hospital.Setting: Fatima Memorial Hospital, Lahore Period: 2007 to 2013. Method: The participantswere 172 women with a diagnosis of idiopathic recurrent miscarriage.12 patients dropped outof the study. Women with 2 or more recurrent fetal losses and after exclusion of all knowncauses of recurrent miscarriage were randomly allocated to receive aspirin alone (n=54),combination treatment aspirin and heparin (n=56) or placebo (n=50 intensive pregnancysurveillance). The results were analyzed by SPSS (version 17) and they were tested by chisquaretest. Results: Out of 160 women who underwent randomization, live birth rate did notdiffer significantly among the three groups. The live birth rate was 70.3% among aspirin onlygroup, 73.2% among aspirin and heparin group and 70% among intensive surveillance group(placebo) with a p value equal to 0.11. No significant differences in secondary outcome wereobserved among three groups. Conclusion: In conclusion, our findings do not support thehypotheses that use of aspirin alone or in combination with enoxapirin improves the live birthrate in women with idiopathic recurrent miscarriages.

The F(ab′)2 fragment of an Aβ-specific monoclonal antibody reduces Aβ deposits in the brain

2005 ◽  
Vol 20 (2) ◽  
pp. 541-549 ◽  
Author(s):  
Yuichi Tamura ◽  
Kenji Hamajima ◽  
Kiyohiko Matsui ◽  
Shunsuke Yanoma ◽  
Masato Narita ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Specific Monoclonal Antibody ◽  
The Brain

scholarly journals Ultrasound-mediated delivery of novel tau-specific monoclonal antibody enhances brain uptake but not therapeutic efficacy

2021 ◽  
Author(s):  
Rinie Bajracharya ◽  
Esteban Cruz ◽  
Juergen Goetz ◽  
Rebecca M Nisbet
Keyword(s):  
Monoclonal Antibody ◽  
Therapeutic Efficacy ◽  
Therapeutic Strategy ◽  
Paracellular Transport ◽  
Brain Endothelial Cells ◽  
Specific Monoclonal Antibody ◽  
Tau Pathology ◽  
Uptake Mechanism ◽  
Transcellular Transport ◽  
The Brain

Tau-specific immunotherapy is an attractive therapeutic strategy for the treatment of Alzheimer's disease and other tauopathies. However, targeting tau effectively remains a considerable challenge due to the restrictive nature of the blood-brain barrier (BBB), which excludes 99.9% of peripherally administered antibodies. We have previously shown that the delivery of tau-specific monoclonal antibody (mAb) with low-intensity scanning ultrasound in combination with intravenously injected microbubbles (SUS+MB) increases the passage of IgG antibodies into the brain. SUS+MB transiently opens tight junctions to allow paracellular transport, but also facilitates transcellular transport, particularly for larger cargoes. However, therapeutic efficacy after enhanced brain delivery has not been explored. To assess whether ultrasound-mediated delivery of tau-specific mAbs leads to an enhanced therapeutic response, K369I tau transgenic K3 mice were passively immunised once weekly for 12 weeks with a novel mAb, RNF5, in combination with SUS+MB. While none of the treatment arms improved behaviour or motor functions in these mice, we found that both RNF5 and SUS+MB treatments on their own reduced tau pathology, but, surprisingly, the combination of both (RNF5+SUS+MB) did not achieve an additive reduction in tau pathology. This was despite observing increased antibody penetration in the brain. Interestingly, a significant fraction of the antibody in the combination treatment was visualized in brain endothelial cells, suggesting that paracellular transport may not be the preferred uptake mechanism for RNF5. Taken altogether, more research is warranted to develop SUS+MB as a delivery modality for anti-tau antibodies.

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