Assessing cross-resistance within the pyrethroids in terms of their interactions with key cytochrome P450 enzymes and resistance in vector populations.

BACKGROUND: It is important to understand whether the potential impact of pyrethroid resistance on malaria control can be mitigated by switching between different pyrethroids or whether cross-resistance within this insecticide class precludes this approach. METHODS: Here we assess the relationships among pyrethroids in terms of their binding affinity to, and depletion by, key cytochrome P450 enzymes (hereafter P450s) that are known to confer metabolic pyrethroid resistance in Anopheles gambiae (s.l.) and An. funestus, in order to identify which pyrethroids may diverge from the others in their vulnerability to resistance. We then investigate whether these same pyrethroids also diverge from the others in terms of resistance in vector populations. RESULTS: We found that the type I and II pyrethroids permethrin and deltamethrin, respectively, are closely related in terms of binding affinity to key P450s, depletion by P450s and resistance within vector populations. Bifenthrin, which lacks the common structural moiety of most pyrethroids, diverged from the other pyrethroids tested in terms of both binding affinity to key P450s and depletion by P450s, but resistance to bifenthrin has rarely been tested in vector populations and was not analysed here. Etofenprox, which also lacks the common structural moiety of most pyrethroids, diverged from the more commonly deployed pyrethroids in terms of binding affinity to key P450s and resistance in vector populations, but did not diverge from these pyrethroids in terms of depletion by the P450s. The analysis of depletion by the P450s indicated that etofenprox may be more vulnerable to metabolic resistance mechanisms in vector populations. In addition, greater resistance to etofenprox was found across Aedes aegypti populations, but greater resistance to this compound was not found in any of the malaria vector species analysed. The results for pyrethroid depletion by anopheline P450s in the laboratory were largely not repeated in the findings for resistance in malaria vector populations. CONCLUSION: Importantly, the prevalence of resistance to the pyrethroids α-cypermethrin, cyfluthrin, deltamethrin, λ-cyhalothrin and permethrin was correlated across malaria vector populations, and switching between these compounds as a tool to mitigate against pyrethroid resistance is not advised without strong evidence supporting a true difference in resistance.

Intestinal permeability and incidence of diarrhea in newborn calves.

Seventy-six newborn Holstein calves (44.4 ± 6.15 kg of body weight) were involved in this study from birth until 21 d of age. Within 2 h after birth, calves received 4 L of maternal colostrum via an esophageal tube. The following 3 meals consisted of 2 L of late colostrum (or transition milk). After that, calves were fed 1.5 L of milk replacer (22.9% CP, 20.1% fat) twice daily. Calves were considered diarrheic when they showed fecal scores ≥ 3 for 3 consecutive days. Then, data from a random subset of 30 calves (45.9 ± 5.47 kg of body weight), 15 that never had diarrhea and 15 that had diarrhea, were used to assess potential associations between intestinal permeability and incidence of diarrhea. On d 0, 7, 14, and 21 of life, intestinal permeability of calves was measured by dosing 2 markers (lactulose and d-mannitol) and assessing their concentration in serum by ultra-HPLC-mass spectrometry. Plasma IgG concentration was measured at birth and at 6 h, 24 h, and 12 d after first colostrum intake, and efficiency of IgG absorption was calculated. Plasma and colostrum IgG contents were determined by radial immunodiffusion and bacterial load in colostrum samples by colony counting. All diarrhea incidences occurred between 7 to 14 d of life. Overall colostrum quality was good, with an IgG content > 100mg/mL, but total bacterial load was slightly high (> 100,000 cfu/mL). However, there were no differences in these 2 parameters between colostrums consumed by calves that did and those that did not incur diarrhea later in life, and efficiency of IgG transfer from colostrum to bloodstream was similar for all calves. Diarrheic calves had greater serum lactulose concentrations than healthy calves throughout the first 21 d of life. Furthermore, diarrheic calves tended to have a greater serum lactulose-to-d-mannitol ratio from birth until 21 d of life compared with healthy calves. In conclusion, calves that incur diarrhea show an altered intestinal permeability within the first 2 h of life compared with those that do not suffer scours.

Arginine supplementation between 41 and 146 days of pregnancy reduces uterine blood flow in dairy heifers.

We hypothesized that arginine (Arg) supplementation during early pregnancy could foster placental vascularization. The objective of this study was to evaluate the effects of Arg supplementation on uterine artery hemodynamics between 40 and 140 days of gestation. At 41 days of gestation, 17 Holstein heifers (448 ± 73.9 kg) were surgically fitted with a catheter in the peritoneal cavity. After surgery, nine heifers received a daily intraperitoneal infusion of 40 mg of Arg/kg of body weight (BW; ARG), whereas the remaining eight heifers received a daily intraperitoneal infusion of saline solution at equivalent volumes as ARG heifers relative to BW (CTRL). Daily infusions took place every 12 hours until heifers reached 146 days of pregnancy. At 41, 62, 83, 104, 125, and 146 days of pregnancy, all heifers were body weighed, bled, and uterine blood flow volume (FV) and other hemodynamics were determined using Doppler ultrasonography. The measurements included heart rate, FV, pulsatility index, and resistance index. Plasma concentrations of amino acids (AAs), nitric oxide, glucose, insulin growth factor, progesterone (P4), growth hormone, and prolactin were analyzed. In a second experiment, we evaluated Arg metabolism when infused either intravenously or intraperitoneally. Overall, FV did not differ between the treatments, but it increased (P < 0.001) with pregnancy day. Uterine blood FV evolved differently between the treatments, with CTRL heifers having a greater (P < 0.05) FV (1104 ± 65.42 mL/min) at 146 days of pregnancy than in ARG heifers (806 ± 65.32 mL/min). Pulsatility index and resistance index decreased throughout pregnancy but did not differ between the treatments. Heart rate was decreased (P < 0.05) in ARG (74 ± 1.4 beats/min) compared with CTRL heifers (81 ± 1.5 beats/min). Plasma concentrations of Arg tended (P < 0.09) to be greater in ARG than those in CTRL heifers, but carnitine, valine, isoleucine, leucine, phenylalanine, and tryptophan were lower (P < 0.05) in ARG than those in CTRL heifers. The proportion of essential AAs (with respect to total AAs) in plasma was greater (P < 0.05) in CTRL (73 ± 2.4%) than that in ARG heifers (65 ± 2.3%). No differences between the treatments were found in plasma prolactin (P = 0.43), insulin growth factor (P = 0.97), glucose (P = 0.45), growth hormone (P = 0.39), or nitric oxide (P = 0.89) concentrations. However, plasma P4 concentration was greater (P < 0.05) in ARG than in CTRL heifers. Contrary to our hypothesis, Arg supplementation did not increase blood flow to the uterus but did change other parameters that could influence placental and fetal growth such as heart rate, maternal concentration of plasma AAs, or P4 synthesis. Furthermore, infusion sites (blood vs. peritoneum) of Arg render different metabolic responses.

Short communication: lying behavior of lactating dairy cows is influenced by lameness especially around feeding time.

Lameness is considered one of the most common welfare and productive problems in dairy cattle. The objective of this study was to evaluate differences in lying behavior between moderately lame and nonlame lactating cows under commercial conditions. Data were collected from 10 free-stall commercial herds, which were feeding on exactly the same ration once daily. All lactating cows were scored for lameness according to a 1 to 5 locomotion scoring system. Only cows with a lameness score between 1 and 4 were considered in the study. In each herd, between 10 and 15 lame cows (scored as 3 or 4) were chosen, and for each lame cow, a nonlame cow (scored as 1) within the same parity and similar days in milk was also selected. Pendant data loggers were then placed on the right hind leg of each cow for 10 d to record lying behavior at 1-min intervals. In addition, the time of feed delivery was recorded in each herd on a daily basis. Total daily lying time, daily number of lying bouts, lying bout duration, laterality (side of recumbence), and lying behavior around feed delivery time were evaluated using a mixed-effects model that accounted for the fixed effects of lameness, days in milk, parity, and the interaction between parity and lameness, plus the random effects of herd. Total daily lying time (721±24.2 min/d) tended to increase with days in milk, but it was not affected by lameness or parity. Likewise, no differences were found in the number of lying bouts (9.6±0.49/d) or laterality (47±2.6% of time lying on the right side). However, the mean bout duration was longer in lame (89.3±3.89 min) compared with nonlame (80.7±3.90 min) cows. It is interesting that lame cows stood up 13 min later than nonlame cows relative to the time when the ration was delivered. In addition, lame cows lay down 19 min earlier than nonlame ones after the feed was delivered, which implies that nonlame cows spent more time standing, and probably eating, than did lame cows. It was concluded that lame cows have longer lying bouts than nonlame animals, and that lying behavior around feed delivery time may be an effective proxy to identify moderately lame cows.