ABSTRACT
INTRODUCTION: Recurrent pregnancy losses (RPL) are common women's health issues. Inflammatory and thrombotic events have been associated with RPL including excessive production of cytokines, in particular TNF-α. However, mechanisms behind gestational losses are not yet fully understood. Sildenafil inhibits phosphodiesterase Type-5 (PDE5). This drug increases intracellular cyclic guanosine monophosphate, having vasodilatory and, more recently described, anti-inflammatory properties. PDE5 is present in murine and human uterus and placenta. Sildenafil is already used clinically for treatment of human fetal growth restriction (FGR). Our objective was to determine if Sildenafil alone or in combination with Heparin had protective effects in pregnant Swiss albino challenged to abort by lipopolysaccharide (LPS). METHODS: Treatments (Sildenafil (50 mg/kg/day), Heparin (500 IU/Kg/day) or Sildenafil + Heparin at the same doses) were initiated the morning of copulation plug detection (gestational day (gd0)). On the 15th day of pregnancy, an intra-peritoneal injection of LPS (100 µg/kg) was administered. Untreated, pregnant mice challenged by LPS served as controls. RESULTS: Assessments at 48 h after LPS revealed that Sildenafil + Heparin prevented fetal loss. Early assessments at 2 h after LPS indicated that the pretreatments prevented induction of inflammatory cytokine production (TNF-α, IL-1ß/NF-κß) and preserved placental histopathology. DISCUSSION: Combined Sildenafil + Heparin therapy was superior to either treatment alone in most analyses. The known safety of Sildenafil and Heparin in human pregnancy suggests that usage of these combined agents may be of value for treatment of patients with impending pregnancy loss or prophylactically in women with a history of recurrent miscarriages.
Subject(s)
Abortion, Spontaneous/prevention & control , Phosphodiesterase 5 Inhibitors/therapeutic use , Sildenafil Citrate/therapeutic use , Abortion, Habitual/drug therapy , Abortion, Spontaneous/pathology , Animals , Disease Models, Animal , Drug Evaluation, Preclinical , Female , Lipopolysaccharides , Male , Mice , Phosphodiesterase 5 Inhibitors/pharmacology , Placenta/drug effects , Placenta/ultrastructure , Pregnancy , Sildenafil Citrate/pharmacologyABSTRACT
Avaliou-se a influência da temperatura de descongelação na integridade de espermatozoides criopreservados de cães. Foram utilizados reprodutores das raças Basset Hound (n=3) e Rottweiler (n=3), submetidos a colheitas de sêmen por manipulação peniana. As amostras de sêmen foram descongeladas a 37ºC/1min (G1) ou 70ºC/6s (G2) e avaliadas quanto à motilidade progressiva, vigor e integridade do acrossoma após 0, 30 e 60 minutos de incubação (37ºC), e ultraestrutura espermática imediatamente após a descongelação. Em todos os tempos de incubação, a motilidade progressiva dos espermatozoides descongelados a 70ºC por 6s (74,6%) foi mais alta (P<0,05) que a dos descongelados a 37ºC por 1min (64,6%). O vigor espermático não diferiu (P>0,05) entre os grupos, e o porcentual de gametas com acrossomas íntegros foi maior (P<0,05) nos espermatozoides do G1 do que no G2. Lesões ultraestruturais foram identificadas nos espermatozoides descongelados de ambos os grupos, em maior quantidade nos gametas do G2. Conclui-se que amostras congeladas de sêmen de cães devam ser descongeladas a 37ºC por 1min.
Aiming to evaluate the influence of the thawing temperature on the viability of canine cryopreserved sperm, Basset Hound (n=3) and Rottweiler (n=3) dogs were used, submitted to semen collected through manual manipulation. Semen samples were thawed at 37ºC during 1min (G1) or at 70ºC during 6s (G2), and evaluated for progressive motility, vigor and acrosome integrity, after 0, 30 e 60 minutes of incubation (37ºC), and sperm ultrastructure immediately after thawing. In all incubation times, the average of progressive motility was higher (P<0.05) in samples from G2 Group (74.6%) than from G1 (64.6%). Sperm vigor had no difference (P>0.05) between groups, and the percentage of gametes with intact acrosome was higher (P<0.05) on sperm cells from G1 than from G2. Ultrastructural changes were identified on dog sperm from both groups, and were observed in higher quantity in gametes from G2 Group. It can be concluded that samples of frozen dog sperm must be thawed at 37°C for 1min.
