The Interplay between Histamine H4 Receptor and the Kidney Function: The Lesson from H4 Receptor Knockout Mice.

Previous studies implicated the histamine H4 receptor in renal pathophysiology. The aim here is to elucidate the role of this receptor on renal function using H4 receptor knockout mice (H4R-/-). Healthy and diabetic H4R-/- mice compared to their C57BL/6J wild-type counterpart for renal function and the expression of crucial tubular proteins. H4R-/- and wild-type mice, matched for ages, showed comparable weight gain curves reaching similar median weight at the end of the study. However, H4R-/- mice displayed a higher basal glycemia. H4R-/- mice showed a lower urine 24 h outflow, and albumin-to-creatinine ratio (ACR) compared to wild-type mice. Consistently, H4R-/- mice presented a higher expression of megalin and a lower basal expression of the sodium-hydrogen exchanger (NHE)3 and aquaporin (AQP)2. According to these basal differences, diabetic H4R-/- mice developed more severe hyperglycemia and a higher 24 h urine volume, but a lower increase in ACR and decrease in urine pH were observed. These events were paralleled by a reduced NHE3 over-expression and megalin loss in diabetic H4R-/- mice. The AQP1 and AQP7 patterns were also different between H4R-/- and wild-type diabetic mice. The collected results highlight the role of the histamine H4 receptor in the control of renal reabsorption processes, particularly albumin uptake.

Efficacy and safety of topical eprinomectin to control Myocoptes musculinus infestation in mice.

Myocoptes musculinus is the most common fur mite identified among laboratory mice; infested mice, in addition to dermatological signs, may also be prone to secondary infections, affecting the outcome of a research trial. This trial was conducted in order to assess the safety and efficacy of a single topical administration of eprinomectin (5mg/kg BW) in a naturally infested laboratory mice colony. A safety trial was conducted on 20 uninfested pregnant females assigned to two groups, receiving eprinomectin and mineral oil, respectively. The mice were examined daily for signs of illness or toxicity; nests were individually weighted at 21 and 28 days postpartum. No acute toxicity was observed, all treated females gave full term delivery and number and mean weight of newborns ranged in the physiological values. To evaluate the efficacy, 20 naturally infested non-pregnant females were divided into two groups, treated as in the safety trial. Animals were observed daily for 15 min until 21 days post-treatment (DPT) and a "pruritus index" (PI: scratching and gnawing acts/mouse/min) was calculated. Pelage examination was performed on DPT 7, 14, 21 and 50. The "PI" was significantly lower in the treated group and mites were eradicated from all infested animals. A single topical administration of eprinomectin at a (high) dosage of 5mg/kg BW was safe and effective to control M. musculinus in mice.

Efficacy and safety of topical eprinomectin to control Myocoptes musculinus infestation in mice / Eficácia e segurança da eprinomectina tópica para controlar a infestação Myocoptes musculinus em camundongos

Myocoptes musculinus is the most common fur mite identified among laboratory mice; infested mice, in addition to dermatological signs, may also be prone to secondary infections, affecting the outcome of a research trial. This trial was conducted in order to assess the safety and efficacy of a single topical administration of eprinomectin (5mg/kg BW) in a naturally infested laboratory mice colony. A safety trial was conducted on 20 uninfested pregnant females assigned to two groups, receiving eprinomectin and mineral oil, respectively. The mice were examined daily for signs of illness or toxicity; nests were individually weighted at 21 and 28 days postpartum. No acute toxicity was observed, all treated females gave full term delivery and number and mean weight of newborns ranged in the physiological values. To evaluate the efficacy, 20 naturally infested non-pregnant females were divided into two groups, treated as in the safety trial. Animals were observed daily for 15 min until 21 days post-treatment (DPT) and a “pruritus index” (PI: scratching and gnawing acts/mouse/min) was calculated. Pelage examination was performed on DPT 7, 14, 21 and 50. The “PI” was significantly lower in the treated group and mites were eradicated from all infested animals. A single topical administration of eprinomectin at a (high) dosage of 5mg/kg BW was safe and effective to control M. musculinus in mice.

Myocoptes musculinus é o ácaro de pele mais comum identificado entre camundongos de laboratório. Camundongos infestados, além de sinais dermatológicos, também podem ser propensos a infecções secundárias, interferindo no resultado de um ensaio de pesquisa. Este estudo foi realizado para avaliar a segurança e eficácia de uma única administração tópica de eprinomectina (5mg / kg PV) em uma colônia de camundongos de laboratório naturalmente infestada. Um estudo de segurança foi realizado em 20 fêmeas prenhes sadias, divididas em dois grupos, recebendo eprinomectina e óleo mineral, respectivamente. Os camundongos foram examinados diariamente para detectar quaisquer sinais da doença ou toxicidade; camundongos recém-nascidos foram pesados individualmente aos 21 e 28 dias pós-parto. Nenhuma toxicidade aguda foi observada. Todas as fêmeas tratadas chegaram ao parto, o número e peso dos recém-nascidos variaram dentro de parâmetros fisiológicos. Para avaliar a eficácia, 20 camundongos não prenhes, naturalmente infestados, foram divididos em dois grupos: tratado e grupo controle não tratado. Os animais foram observados diariamente durante 15 minutos até os 21 dias pós- tratamento (DPT) e um índice de prurido (IP) - arranhões e ato de roer / camundongo / min) foi calculado. Exame da pelagem foi realizado em DPT 7, 14, 21 e 50. O IP foi significativamente menor no grupo tratado, e os ácaros foram erradicados de todos os animais infestados. Uma única administração tópica de eprinomectina, na dose de 5mg / kg de peso corporal, foi segura e eficaz no controle de M. musculinus em camundongos.