Comprehensive and compassionate responses for opioid use disorder among pregnant and parenting women.

Pregnant and parenting women with opioid use disorder face multiple challenges to recovery. Trauma histories, poverty, stigma and discrimination, and lack of access to treatment intersect to marginalise this population. It is important that pregnant and parenting women with opioid use disorder receive comprehensive care to improve their health, the health of their child(ren), and prevent the intergenerational transmission of opioid and other substance use disorders. For nearly 50 years the Maternal Addiction Treatment, Education, and Research program has provided an evolving and expanding range of comprehensive services for treating opioid and other substance use disorders in this population. In this review the rationale for, and processes by which, key components of a comprehensive approach are discussed. These components include patient navigation for access to care, low-barrier medications for opioid use disorder, effective trauma-responsive therapy, prenatal and well-child healthcare, and other support services that make it possible for pregnant and parenting women to engage in treatment and improve the health of the entire family. Additionally, a method for supporting staff to build resilience and reduce fatigue and burnout is discussed. These components comprise an effective model of care for pregnant and parenting women with opioid and other substance use disorders.

In vitro activity of the hydroethanolic extract and biflavonoids isolated from Selaginella sellowii on Leishmania (Leishmania) amazonensis

This study is the first phytochemical investigation of Selaginella sellowii and demonstrates the antileishmanial activity of the hydroethanolic extract from this plant (SSHE), as well as of the biflavonoids amentoflavone and robustaflavone, isolated from this species. The effects of these substances were evaluated on intracellular amastigotes of Leishmania (Leishmania) amazonensis, an aetiological agent of American cutaneous leishmaniasis. SSHE was highly active against intracellular amastigotes [the half maximum inhibitory concentration (IC50) = 20.2 µg/mL]. Fractionation of the extract led to the isolation of the two bioflavonoids with the highest activity: amentoflavone, which was about 200 times more active (IC50 = 0.1 μg/mL) and less cytotoxic than SSHE (IC50 = 2.2 and 3 μg/mL, respectively on NIH/3T3 and J774.A1 cells), with a high selectivity index (SI) (22 and 30), robustaflavone, which was also active against L. amazonensis (IC50 = 2.8 µg/mL), but more cytotoxic, with IC50 = 25.5 µg/mL (SI = 9.1) on NIH/3T3 cells and IC50 = 3.1 µg/mL (SI = 1.1) on J774.A1 cells. The production of nitric oxide (NO) was lower in cells treated with amentoflavone (suggesting that NO does not contribute to the leishmanicidal mechanism in this case), while NO release was higher after treatment with robustaflavone. S. sellowii may be a potential source of biflavonoids that could provide promising compounds for the treatment of cutaneous leishmaniasis.

In vitro activity of the hydroethanolic extract and biflavonoids isolated from Selaginella sellowii on Leishmania (Leishmania) amazonensis.

This study is the first phytochemical investigation of Selaginella sellowii and demonstrates the antileishmanial activity of the hydroethanolic extract from this plant (SSHE), as well as of the biflavonoids amentoflavone and robustaflavone, isolated from this species. The effects of these substances were evaluated on intracellular amastigotes of Leishmania (Leishmania) amazonensis, an aetiological agent of American cutaneous leishmaniasis. SSHE was highly active against intracellular amastigotes [the half maximum inhibitory concentration (IC50) = 20.2 µg/mL]. Fractionation of the extract led to the isolation of the two bioflavonoids with the highest activity: amentoflavone, which was about 200 times more active (IC50 = 0.1 µg/mL) and less cytotoxic than SSHE (IC50 = 2.2 and 3 µg/mL, respectively on NIH/3T3 and J774.A1 cells), with a high selectivity index (SI) (22 and 30), robustaflavone, which was also active against L. amazonensis (IC50 = 2.8 µg/mL), but more cytotoxic, with IC50 = 25.5 µg/mL (SI = 9.1) on NIH/3T3 cells and IC50 = 3.1 µg/mL (SI = 1.1) on J774.A1 cells. The production of nitric oxide (NO) was lower in cells treated with amentoflavone (suggesting that NO does not contribute to the leishmanicidal mechanism in this case), while NO release was higher after treatment with robustaflavone. S. sellowii may be a potential source of biflavonoids that could provide promising compounds for the treatment of cutaneous leishmaniasis.

Early life LiCl-pilocarpine-induced status epilepticus reduces acutely hippocampal glutamate uptake and Na+/K+ ATPase activity.

Status epilepticus-induced hippocampal neuronal loss is mainly associated with excitotoxicity induced by increased levels of extracellular glutamate which is normally neutralized by high-affinity uptake mechanism. The energy source for the glutamate uptake is the electrochemical Na(+) gradient maintained by Na(+)/K(+) ATPase pump. In this study, we investigated the effect of early-life-induced status epilepticus on hippocampal Na(+)/K(+) ATPase activity and glutamate uptake. Rat pups 15 days old were injected i.p. with LiCl (3 mEq/kg) 12-18 h prior to s.c. pilocarpine administration (60 mg/kg). Hippocampal Na(+)/K(+) ATPase activity and glutamate uptake were evaluated 1.5, 12 and 24 h after SE induction. LiCl-pilocarpine-induced SE decreased Na(+)/K(+) ATPase activity and glutamate uptake by 42 and 38%, respectively, 1.5 h after SE induction. However, 12 and 24 h after SE induction the pump activity and glutamate uptake returned to control levels. SE early in life increased hippocampal number of degenerating neurons in the CA1 subfield and dentate gyrus 24 h after SE induction. In conclusion, SE induced early in life causes short-term disruption in hippocampal Na(+)/K(+) ATPase activity and glutamate uptake, which may be related to neuronal death found in CA1 subfield.

[Effects of different dilution levels on bull- and ejaculate related variability of plasmamembran integrity, acrosomal damage and DNA-integrity of cryopreserved bull spermatozoa]. / Effekte der unterschiedlich starken Verdünnung auf die individuell- und ejakulatbedingte Variabilität der Plasmamembranintegrität, des akrosomalen Status und die DNA-Integrität kryokonservierten Bullenspermas.

In this study the effects of three different dilution levels (60, 30 and 15 Mio/ml) on quality of cryopreserved bovine sperm were investigated. Particularly it was tested, if effects of dilution in regard to sperm quality were related to the factors bull or ejaculate. The following parameters were analysed in four ejaculates each of 42 bulls: percentage of plasma membrane intact sperm (PMI), percentage of sperm with acrosomal damage (AS) as well as percentage of sperm with a high DNA-fragmentation index (DFI%) following cryopreservation. PMI-values decreased (p < 0.05) with increasing degree of dilution. AS-values were not influenced (p > 0.05) by dilution level. There was a decline in DFI% (p <0.05) with increasing dilution of the ejaculate. Coefficient of variation for PMI, AS and DFI% were not (p > 0.05) influenced by dilution. The effects of the factor ejaculate on the variabilities of PMI and AS were higher than the effects of the factor bull. Variability of DFI% depended at the highest dilution level more on the factor bull and in the lowest dilution level more on the factor ejaculate. In conclusion, these results show that dilution of sperm has positive as well as negative effects on sperm quality. With increasing dilution the effect of the factor bull on plasma membrane- and acrosomal integrity.

Effects of early-life LiCl-pilocarpine-induced status epilepticus on memory and anxiety in adult rats are associated with mossy fiber sprouting and elevated CSF S100B protein.

PURPOSE: This study investigated putative correlations among behavioral changes and: (1) neuronal loss, (2) hippocampal mossy fiber sprouting, and (3) reactive astrogliosis in adult rats submitted to early-life LiCl-pilocarpine-induced status epilepticus (SE). METHODS: Rats (P15) received LiCl (3 mEq/kg, i.p.) 12-18 h prior pilocarpine (60 mg/kg; s.c.). At adulthood, animals were submitted to behavioral tasks and after the completion of tasks biochemical and histological analysis were performed. RESULTS: In SE group, it was observed an increased number of degenerating neurons in the CA1 subfield and in the hilus of animals 24 h after SE. At adulthood, SE group presented an aversive memory deficit in an inhibitory avoidance task and the animals that presented lower latency to the step down showed a higher score for mossy fiber sprouting. In the light-dark exploration task, SE rats returned less and spent less time in the light compartment and present an increased number of risk assessment behavior (RA). There was a negative correlation between the time spent in the light compartment and the score for mossy fiber sprouting and a positive correlation between score for mossy fiber sprouting and number of RA. LiCl-pilocarpine-treated animals showed higher levels of S100B immunocontent in the CSF as well as a positive correlation between the score for sprouting and the GFAP immunocontent in the CA1 subfield, suggesting an astrocytic response to neuronal injury. CONCLUSIONS: We showed that LiCl-pilocarpine-induced SE during development produced long-lasting behavioral abnormalities, which might be associated with mossy fiber sprouting and elevated CSF S100B levels at adulthood.