The effect of isosorbide dinitrate on uterine and ovarian blood flow in cycling and early pregnant mares: A pilot study

Kimura

et al. 2021

JPM

For more than three decades, enhanced permeability and retention (EPR)-effect-based nanomedicines have received considerable attention for tumor-selective treatment of solid tumors. However, treatment of advanced cancers remains a huge challenge in clinical situations because of occluded or embolized tumor blood vessels, which lead to so-called heterogeneity of the EPR effect. We previously developed a method to restore impaired blood flow in blood vessels by using nitric oxide donors and other agents called EPR-effect enhancers. Here, we show that two novel EPR-effect enhancers—isosorbide dinitrate (ISDN, Nitrol®) and sildenafil citrate—strongly potentiated delivery of three macromolecular drugs to tumors: a complex of poly(styrene-co-maleic acid) (SMA) and cisplatin, named Smaplatin® (chemotherapy); poly(N-(2-hydroxypropyl)methacrylamide) polymer-conjugated zinc protoporphyrin (photodynamic therapy and imaging); and SMA glucosamine-conjugated boric acid complex (boron neutron capture therapy). We tested these nanodrugs in mice with advanced C26 tumors. When these nanomedicines were administered together with ISDN or sildenafil, tumor delivery and thus positive therapeutic results increased two- to four-fold in tumors with diameters of 15 mm or more. These results confirmed the rationale for using EPR-effect enhancers to restore tumor blood flow. In conclusion, all EPR-effect enhancers tested showed great potential for application in cancer therapy.

Section: Introductionmentioning

confidence: 99%

EPR-Effect Enhancers Strongly Potentiate Tumor-Targeted Delivery of Nanomedicines to Advanced Cancers: Further Extension to Enhancement of the Therapeutic Effect

Kimura

et al. 2021

JPM

“…Classically, PGF 2α induces luteolysis by decreasing luteal blood flow, resulting in hypoxia; however, before the initial steps of the luteolytic cascade, PGF 2α increases luteal blood flow and CL vascularization [ 28 , 29 ]. Additionally, the increased blood serum E 2 and NO levels in NGPG and HNGPG may contribute to this effect through their vasodilation effects [ 30 , 31 ]. These findings support the relevance of the PGF 2α in nanoform for the expected role of this injection even when the dose is reduced to half of the conventional dose.…”

Section: Discussionmentioning

confidence: 99%

Nanodelivery System for Ovsynch Protocol Improves Ovarian Response, Ovarian Blood Flow Doppler Velocities, and Hormonal Profile of Goats

Hashem

El‐Sherbiny

Fathi

et al. 2022

Animals

Fifteen cyclic, multiparous goats were equally stratified and received the common Ovsynch protocol (GPG: intramuscular, IM, injection of 50 mg gonadorelin, followed by an IM injection of 125 µg cloprostenol 7 days later, and a further IM injection of 50 mg gonadorelin 2 days later) or the Ovsynch protocol using nanofabricated hormones with the same dosages (NGPG) or half dosages (HNGPG) of each hormone. The ovarian structures and ovarian and luteal artery hemodynamic indices after each injection of the Ovsynch protocol using B-mode, color, and spectral Doppler scanning were monitored. Levels of blood serum progesterone (P4), estradiol (E2), and nitric oxide (NO) were determined. After the first gonadotrophin-releasing hormone (GnRH) injection, the number of large follicles decreased (p = 0.02) in NGPG and HNGPG, compared with GPG. HNGPG resulted in larger corpus luteum (CL) diameters (p = 0.001), and improved ovarian and luteal blood flow, compared with GPG and NGPG. Both NGPG and HNGPG significantly increased E2 and NO levels compared with GPG. HNGPG increased (p < 0.001) P4 levels compared with GPG, whereas NGPG resulted in an intermediate value. After prostaglandin F2α (PGF2α) injection, HNGPG had the largest diameter of CLs (p = 0.001) and significantly improved ovarian blood flow compared with GPG and NGPG. Both NGPG and HNGPG increased (p = 0.007) NO levels, compared with GPG. E2 level was increased (p = 0.028) in HNGPG, compared with GPG, whereas NGPG resulted in an intermediate value. During the follicular phase, HNGPG increased (p = 0.043) the number of medium follicles, shortened (p = 0.04) the interval to ovulation, and increased (p < 0.001) ovarian artery blood flow and levels (p < 0.001) of blood serum P4, E2, and NO, compared with GPG and NGPG. During the luteal phase, the numbers of CLs were similar among different experimental groups, whereas the diameter of CLs, luteal blood flow, and levels of blood serum P4 and NO increased (p < 0.001) in HNGPG, compared with GPG and NGPG. Conclusively, the nanodelivery system for the Ovsynch protocol could be recommended as a new strategy for improving estrous synchronization outcomes of goats while enabling lower hormone dose administration.

“…Diante disso, os autores concluíram que nenhum benefício imediato na administração da Pentoxifilina em éguas prenhes foi observado sobre o fluxo da artérias uterinas. Zoller et al (2016) (2015), lesões degenerativas do útero estão associadas a infertilidade ou subfertilidade. O processo degenerativo uterino, caracterizado pela intensificação das disfunções vasculares e aumento na severidade de fibrose endometrial e periglandular, se deve a grande distensão uterina no transcurso da gestação e regressão pós-parto.…”

Section: Análise Uterinaunclassified

Principais Aplicações Da Ultrassonografia Modo Doppler Na Reprodução Em Éguas

Sá¹,

Dutra²,

Nogueira³

et al. 2017

Enci Bio

RESUMOA ultrassonografia modo Doppler tem sido utilizada para acompanhar e avaliar a vascularização do sistema reprodutor de fêmeas equinas. Trata-se de uma tecnologia emergente na Medicina Veterinária que visa análise da vascularização diretamente no local de interesse. Esta ferramenta de análise fornece não apenas informações atuais da estrutura, bem como é capaz de predizer condições futuras, como o potencial de dominância de um folículo ou ainda sua capacidade ovulatória. O modo Power-flow possibilita estudar vasos de pequeno calibre e tortuosos, numerosos no sistema reprodutor de grandes animais. Já o modo espectral é considerado inadequado devido aos sinais de Doppler no endométrio. Para análise do fluxo sanguíneo do corpo lúteo, o modo Doppler consegue detectar alterações durante o ciclo estral e diferenças individuais na vascularização. O exame da estrutura lútea por meio da ultrassonografia modo Doppler de éguas receptoras é uma ferramenta importante, pois auxilia na seleção de animais com perfil sérico de progesterona adequado para o desenvolvimento do embrião e manutenção da gestação. Outra aplicabilidade da ultrassonografia modo Doppler encontrada na literatura consiste na análise de folículos hemorrágicos anovulatórios, que desenvolveram tecido luteal bem vascularizado como indicado através da ecotextura, sinais Doppler colorido e pela produção de progesterona em níveis próximos ao normal. Sendo assim, esta técnica apresenta inúmeras aplicações como método complementar de diagnóstico sobre o sistema reprodutor de éguas. Apesar dos estudos já existentes, novos estudos são necessários visando preencher as lacunas ainda existentes sobre aplicabilidade do modo Doppler.