Multitarget anti-parasitic activities of isoquinoline alkaloids isolated from Hippeastrum aulicum (Amaryllidaceae).

BACKGROUND: Chagas disease and leishmaniasis affect a significant portion of the Latin American population and still lack efficient treatments. In this context, natural products emerge as promising compounds for developing more effective therapies, aiming to mitigate side effects and drug resistance. Notably, species from the Amaryllidaceae family emerge as potential reservoirs of antiparasitic agents due to the presence of diverse biologically active alkaloids. PURPOSE: To assess the anti-Trypanosoma cruzi and anti-Leishmania infantum activity of five isolated alkaloids from Hippeastrum aulicum Herb. (Amaryllidaceae) against different life stages of the parasites using in silico and in vitro assays. Furthermore, molecular docking was employed to evaluate the interaction of the most active alkaloids. METHODS: Five natural isoquinoline alkaloids isolated in suitable quantities for in vitro testing underwent preliminary in silico analysis to predict their potential efficacy against Trypanosoma cruzi (amastigote and trypomastigote forms) and Leishmania infantum (amastigote and promastigote forms). The in vitro antiparasitic activity and mammalian cytotoxicity were investigated with a subsequent comparison of both analysis (in silico and in vitro) findings. Additionally, this study employed the molecular docking technique, utilizing cruzain (T. cruzi) and sterol 14α-demethylase (CYP51, L. infantum) as crucial biological targets for parasite survival, specifically focusing on compounds that exhibited promising activities against both parasites. RESULTS: Through computational techniques, it was identified that the alkaloids haemanthamine (1) and lycorine (8) were the most active against T. cruzi (amastigote and trypomastigote) and L. infantum (amastigote and promastigote), while also revealing unprecedented activity of alkaloid 7­methoxy-O-methyllycorenine (6). The in vitro analysis confirmed the in silico tests, in which compound 1 presented the best activities against the promastigote and amastigote forms of L. infantum with half-maximal inhibitory concentration (IC50) 0.6 µM and 1.78 µM, respectively. Compound 8 exhibited significant activity against the amastigote form of T. cruzi (IC50 7.70 µM), and compound 6 demonstrated activity against the trypomastigote forms of T. cruzi and amastigote of L. infantum, with IC50 values of 89.55 and 86.12 µM, respectively. Molecular docking analyses indicated that alkaloids 1 and 8 exhibited superior interaction energies compared to the inhibitors. CONCLUSION: The hitherto unreported potential of compound 6 against T. cruzi trypomastigotes and L. infantum amastigotes is now brought to the forefront. Furthermore, the acquired dataset signifies that the isolated alkaloids 1 and 8 from H. aulicum might serve as prototypes for subsequent structural refinements aimed at the exploration of novel leads against both T. cruzi and L. infantum parasites.

Remote nutrition care during the first wave of COVID-19 pandemic: Did it impact nutrition therapy goals?

BACKGROUND AND AIMS: Nutrition societies recommended remote hospital nutrition care during the coronavirus disease 2019 (COVID-19) pandemic. However, the pandemic's impact on nutrition care quality is unknown. We aimed to evaluate the association between remote nutrition care during the first COVID-19 wave and the time to start and achieve the nutrition therapy (NT) goals of critically ill patients. METHODS: A cohort study was conducted in an intensive care unit (ICU) that assisted patients with COVID-19 between May 2020 and April 2021. The remote nutrition care lasted approximately 6 months, and dietitians prescribed the nutrition care based on medical records and daily telephone contact with nurses who were in direct contact with patients. Data were retrospectively collected, patients were grouped according to the nutrition care delivered (remote or in person), and we compared the time to start NT and achieve the nutrition goals. RESULTS: One hundred fifty-eight patients (61.5 ± 14.8 years, 57% male) were evaluated, and 54.4% received remote nutrition care. The median time to start NT was 1 (1-3) day and to achieve the nutrition goals was 4 (3-6) days for both groups. The percentage of energy and protein prescribed on day 7 of the ICU stay concerning the requirements did not differ between patients with remote and patients with in-person nutrition care [95.5% ± 20.4% × 92.1% ± 26.4% (energy) and 92.9% ± 21.9% × 86.9% ± 29.2% (protein); P > 0.05 for both analyses]. CONCLUSION: Remote nutrition care in patients critically ill with COVID-19 did not impact the time to start and achieve the NT goals.

Multitarget anti-parasitic activities of isoquinoline alkaloids isolated from Hippeastrum aulicum (Amaryllidaceae)

Background Chagas disease and leishmaniasis affect a significant portion of the Latin American population and still lack efficient treatments. In this context, natural products emerge as promising compounds for developing more effective therapies, aiming to mitigate side effects and drug resistance. Notably, species from the Amaryllidaceae family emerge as potential reservoirs of antiparasitic agents due to the presence of diverse biologically active alkaloids. Purpose To assess the anti-Trypanosoma cruzi and anti-Leishmania infantum activity of five isolated alkaloids from Hippeastrum aulicum Herb. (Amaryllidaceae) against different life stages of the parasites using in silico and in vitro assays. Furthermore, molecular docking was employed to evaluate the interaction of the most active alkaloids. Methods Five natural isoquinoline alkaloids isolated in suitable quantities for in vitro testing underwent preliminary in silico analysis to predict their potential efficacy against Trypanosoma cruzi (amastigote and trypomastigote forms) and Leishmania infantum (amastigote and promastigote forms). The in vitro antiparasitic activity and mammalian cytotoxicity were investigated with a subsequent comparison of both analysis (in silico and in vitro) findings. Additionally, this study employed the molecular docking technique, utilizing cruzain (T. cruzi) and sterol 14α-demethylase (CYP51, L. infantum) as crucial biological targets for parasite survival, specifically focusing on compounds that exhibited promising activities against both parasites. Results Through computational techniques, it was identified that the alkaloids haemanthamine (1) and lycorine (8) were the most active against T. cruzi (amastigote and trypomastigote) and L. infantum (amastigote and promastigote), while also revealing unprecedented activity of alkaloid 7‑methoxy-O-methyllycorenine (6). The in vitro analysis confirmed the in silico tests, in which compound 1 presented the best activities against the promastigote and amastigote forms of L. infantum with half-maximal inhibitory concentration (IC50) 0.6 µM and 1.78 µM, respectively. Compound 8 exhibited significant activity against the amastigote form of T. cruzi (IC50 7.70 µM), and compound 6 demonstrated activity against the trypomastigote forms of T. cruzi and amastigote of L. infantum, with IC50 values of 89.55 and 86.12 µM, respectively. Molecular docking analyses indicated that alkaloids 1 and 8 exhibited superior interaction energies compared to the inhibitors. Conclusion The hitherto unreported potential of compound 6 against T. cruzi trypomastigotes and L. infantum amastigotes is now brought to the forefront. Furthermore, the acquired dataset signifies that the isolated alkaloids 1 and 8 from H. aulicum might serve as prototypes for subsequent structural refinements aimed at the exploration of novel leads against both T. cruzi and L. infantum parasites.

The influence of weaning age and biocholine supplementation to post-weaning growth and puberty in Brangus heifers.

This experiment was conducted to determine the effect of earlier weaning in addition to biocholine supplementation on age at puberty of Brangus heifers. Brangus calves were randomized and divided into three weaning ages groups, at 30 (Hyper-early weaning; HW), 75 (Early weaning; EW) and 180 days (Conventional weaning; CW). Then, calves were supplemented using the additive Biocholine (BIO) or not (CON). Animals were subjected to puberty induction and the presence of estrus was observed for 7 days. In addition, transrectal ultrasonography was performed to assess the ovarian activity and the presence of corpus luteum to determine heifer puberty. We also evaluated the body weight (BW; Kg), hip height (HH; cm), thoracic perimeter (TP; cm) and BW:HH ratio during the experimental period. BIO group showed higher ADG (>226 g/day) when the animals were exposed to ryegrass pasture compared to CON (P < 0.05). We observed an interaction between weaning x biocholine and CW-BIO heifers showed greater HH more compared to CW-CON (P < 0.05). Overall, animals that have reached puberty at day 8 after puberty induction showed 331.0 ± 5.04 kg BW, 122.0 ± 0.56 cm HH and 165.4 ± 0.75 cm TP and 2.7 ± 0.03 BW:HH. At the time of ovulation detection, the heifers from the HW group had 32.1 kg BW, 3.93 cm HH and 0.18 cm BW:HH greater compared to CW (P < 0.05). The BIO supplementation together with ryegrass pasture, led to an increase in ADG weight throughout the evaluated period. We concluded that HW heifers showed an adequate body development throughout the experimental period until puberty appearance at the same age as others weaned groups.

Decline of nutritional status in the first week of hospitalisation predicts longer length of stay and hospital readmission during 6-month follow-up.

Nutritional status (NS) monitoring is an essential step of the nutrition care process. To assess changes in NS throughout hospitalisation and its ability to predict clinical outcomes, a prospective cohort study with patients over 18 years of age was conducted. The Subjective Global Assessment (SGA) was performed within 48 h of admission and 7 d later. For each patient, decline in NS was assessed by two different methods: changes in SGA category and severe weight loss alone (≥2 % during the first week of hospitalisation). Patients were followed up until discharge to assess length of hospital stay (LOS) and in-hospital mortality and contacted 6 months post-discharge to assess hospital readmission and death. Out of the 601 patients assessed at admission, 299 remained hospitalised for at least 7 d; of those, 16·1 % had a decline in SGA category and 22·8 % had severe weight loss alone. In multivariable analysis, decline in SGA category was associated with 2-fold (95 % CI 1·06, 4·21) increased odds of prolonged LOS and 3·6 (95 % CI 1·05, 12·26) increased odds of hospital readmission at 6 months. Severe weight loss alone was associated with 2·5-increased odds (95 % CI 1·40, 4·64) of prolonged LOS. In conclusion, deterioration of NS was more often identified by severe weight loss than by decline in SGA category. While both methods were associated with prolonged LOS, only changes in the SGA predicted hospital readmission. These findings reinforce the importance of nutritional monitoring and provide guidance for further research to prevent short-term NS deterioration from being left undetected.

Hydrogels Containing Nanocapsules and Nanoemulsions of Tea Tree Oil Provide Antiedematogenic Effect and Improved Skin Wound Healing.

In previous works, we developed nanocapsules and nanoemulsions containing the tea tree oil. The aim of this work was to prepare and characterize hydrogels containing these nanocarriers, and to evaluate their in vivo efficacy in protecting skin damage induced by UVB and cutaneous wound healing. Hydrogels were prepared using Carbopol Ultrez and their physicochemical characteristics were evaluated: macroscopic analysis, pH, spreadability and rheological properties. The in vivo antiedematogenic effect was evaluated by ear thickness measurement after UVB-irradiation. In order to evaluate healing action of hydrogels, we investigated the regression of the cutaneous lesion in rats. Hydrogels showed homogeneous aspect and pH values between 5.6-5.8 and a non-Newtonian behavior. The presence of nanocapsules and nanoemulsions in hydrogels did not change their spreadability profile. The inclusion of tea tree oil in the nanocapsules and nanoemulsions allowed reducing the edema induced by UVB exposure. Hydrogel containing nanocapsules presented a higher reduction of the wound area compared to the hydrogel containing nanoemulsions and hydrogel containing allantoin. This study shows the feasibility of obtained dermatological formulations containing the tea tree oil associated in nanostructured systems. These formulations represent a promising approach to topical treatment of inflammatory disorders and wound healing.