Search

Ultra-long-acting delivery platforms for HIV pre-exposure prophylaxis (PrEP) may increase adherence and maximize public health benefit. We report on an injectable, biodegradable, and removable in-situ forming implant (ISFI) that is administered subcutaneously and can release the integrase inhibitor cabotegravir (CAB) above protective benchmarks for more than 6 months. CAB ISFIs are well-tolerated in female mice and female macaques showing no signs of toxicity or chronic inflammation. In macaques, median plasma CAB concentrations exceed established PrEP protection benchmarks within 3 weeks and confer complete protection against repeated rectal SHIV challenges. Implant removal via a small incision in 2 macaques at week 12 results in a 7- to 48-fold decrease in plasma CAB levels within 72 hours. Modeling to translate CAB ISFI dosing suggests that a 3 mL injection would exceed protective benchmarks in humans for over 5 months post administration. Our results support the clinical advancement of CAB ISFIs for ultra-long-acting PrEP in humans. In this study, the authors developed an ultra-long-acting injectable, biodegradable, and removable in-situ forming implant delivering cabotegravir (CAB ISFI). CAB ISFI was well tolerated and protected against multiple rectal SHIV challenges in female macaques. [ABSTRACT FROM AUTHOR]

Ultra-long-acting delivery platforms for HIV pre-exposure prophylaxis (PrEP) may increase adherence and maximize public health benefit. We report on an injectable, biodegradable, and removable in-situ forming implant (ISFI) that is administered subcutaneously and can release the integrase inhibitor cabotegravir (CAB) above protective benchmarks for more than 6 months. CAB ISFIs are well-tolerated in female mice and female macaques showing no signs of toxicity or chronic inflammation. In macaques, median plasma CAB concentrations exceed established PrEP protection benchmarks within 3 weeks and confer complete protection against repeated rectal SHIV challenges. Implant removal via a small incision in 2 macaques at week 12 results in a 7- to 48-fold decrease in plasma CAB levels within 72 hours. Modeling to translate CAB ISFI dosing suggests that a 3 mL injection would exceed protective benchmarks in humans for over 5 months post administration. Our results support the clinical advancement of CAB ISFIs for ultra-long-acting PrEP in humans. In this study, the authors developed an ultra-long-acting injectable, biodegradable, and removable in-situ forming implant delivering cabotegravir (CAB ISFI). CAB ISFI was well tolerated and protected against multiple rectal SHIV challenges in female macaques. [ABSTRACT FROM AUTHOR]

Syrian hamsters are a key animal model of SARS-CoV-2 and other respiratory viruses and are useful for the evaluation of associated medical countermeasures. Delivery of an infectious agent or intervention to the respiratory tract mirrors natural routes of exposure and allows for the evaluation of clinically relevant therapeutic administration. The data to support instillation or inoculation volumes are important both for optimal experimental design and to minimize or avoid effects of diluent alone, which may compromise both data interpretation and animal welfare. Here we investigate four intranasal (IN) instillation volumes in hamsters (50, 100, 200, or 400 µL). The animals were monitored daily, and a subset were serially euthanized at one of four pre-determined time-points (1, 3, 7, and 14 days post-instillation). Weight, temperature, oxygen saturation, CBC, radiographs, and respiratory tissue histopathology were assessed to determine changes associated with instillation volume alone. With all the delivery volumes, we found no notable differences between instilled and non-instilled controls in all of the parameters assessed, except for histopathology. In the animals instilled with 200 or 400 µL, inflammation associated with foreign material was detected in the lower respiratory tract indicating that higher volumes may result in aspiration of nasal and/or oropharyngeal material in a subset of animals, resulting in IN instillation-associated histopathology. [ABSTRACT FROM AUTHOR]

Low endogenous estrogen action causes several injuries. Medicinal plants, such as flaxseed and mulberry, contain substances that have been shown to be effective to the organism. The aim was to verify the effects of flaxseed and/or mulberry extracts on ovariectomized Wistar rats. The animals received supplements of extracts and estrogen or saline by gavage for 60 days and were weighed weekly. Vaginal wash, blood, pituitary, uterus, liver, and kidneys were collected. Phenolic compounds and the antioxidant activity of the extracts, lipid profile, uric acid, liver enzymes, and pituitary weight were measured. Histomorphometric for uterine wall and histopathological analyses for liver and kidney were performed. Flaxseed and mulberry extracts showed great antioxidant activity and large amounts of phenolic compounds. The treatment with extracts had less weight gain, increased pituitary weight, the predominance of vaginal epithelial cells, and reduced TC, LDL-c and lipase activity, similar to estrogen animals. Estrogen or flaxseed + mulberry animals reduced VLDL-c and TAG. HDL-c, uric acid, and liver enzymes did not differ. Estrogen or extracts demonstrated trophic action on the endometrial thickness and have not shown hepatotoxicity or nephrotoxicity. We suggested the beneficial effects of flaxseed and mulberry extract as an alternative to reduce and/or prevent the negative effects caused by low estrogenic action. [ABSTRACT FROM AUTHOR]

Background: Candlenut (CN) has been used indiscriminately for weight loss. In vivo effects of CN in different doses are scarce. Objective: To evaluate the effects of CN ingestion in obese rats. Design: Thirty animals (obese and non-obese) received one of three different types of treatments: placebo, CN ingestion in a popular therapeutic regimen (8 days with oral administration of 0.2 mg/kg followed by 20 days with doses of 0.4 mg/kg), and ingestion of a doubled popular dose—called 2CN. Treatment was maintained for 28 days. Results: The fatty acid profile of CN indicated mainly linolelaidic and palmitoleic acids. Rats receiving CN and 2CN showed reduced plasmatic levels of glucose and lipoproteins (p < 0.05). A dose-dependent carcass fat reduction was observed (p < 0.05). Blood levels of aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) reduced with CN and increased with 2CN doses (p < 0.05). Alanine aminotransferase (ALT) and the atherogenic index remained similar among all treatments (p > 0.05). Hepatic vacuolation decreased with CN, but the 2CN dose produced mononuclear leucocyte infiltrate. Conclusions: Although CN presented beneficial effects on the metabolism of rats, it also caused increased risk of liver damage. [ABSTRACT FROM AUTHOR]