Desensitization to trimethoprim-sulfamethoxazole in a toxoplasmic encephalitis patient who was intolerant to conventional treatments.

Toxoplasma gondii is an obligate intracellular protozoan that causes toxoplasmic encephalitis (TE) in immunocompromised patients. We describe a case of a 29-year-old Japanese man presenting with headache and vomiting. He had previously been diagnosed with human immunodeficiency virus infection. Magnetic resonance imaging identified some nodules in his brain. We suspected TE and began treatment successively with parenteral trimethoprim-sulfamethoxazole (TMP/SMX) plus clindamycin. After that, we switched to pyrimethamine plus sulfadiazine (PMT/SDZ) because these drugs are the first-line treatment for TE. Because the patient experienced nausea and vomiting, PMT/SDZ was replaced with TMP/SMX, atovaquone, and clindamycin. However, the patient could not tolerate them owing to their adverse reactions. Thus, we attempted oral desensitization to TMP/SMX to treat his TE. We began desensitization with 0.4/2 mg of TMP/SMX. The patient experienced morbilliform rash and elevated aminotransferase levels. Therefore, we administered a glycyrrhizin and an antihistamine and continued the last tolerable dose until these symptoms improved. After 37 days, we achieved desensitization to 160/800 mg of TMP/SMX, and the patient's symptoms improved. After using nested-polymerase chain reaction to identify T. gondii DNA in his frozen cerebrospinal fluid, which was collected at admission, his diagnosis was confirmed as TE. This might be the first case to attempt desensitization to TMP/SMX to treat TE.

Effect of Diclazuril on the Bursa of Fabricius Morphology and SIgA Expression in Chickens Infected with Eimeria tenella.

The effects of diclazuril on the bursa of Fabricius (BF) structure and secretory IgA (SIgA) expression in chickens infected with Eimeria tenella were examined. The morphology of the BF was observed by hematoxylin and eosin staining, while ultrastructural changes were monitored by transmission electron microscopy. E. tenella infection caused the BF cell volumes to decrease, irregularly arranged, as well as, enlargement of the intercellular space. Diclazuril treatment alleviated the physical signs of damages associated with E. tenella infection. The SIgA expression in BF was analyzed by immunohistochemistry technique. The SIgA expression increased significantly by 350.4% (P<0.01) after E. tenella infection compared to the normal control group. With the treatment of diclazuril, the SIgA was relatively fewer in the cortex, and the expression level was significantly decreased by 46.7% (P<0.01) compared with the infected and untreated group. In conclusion, E. tenella infection in chickens induced obvious harmful changes in BF morphological structure and stimulated the expression of SIgA in the BF. Diclazuril treatment effectively alleviated the morphological changes. This result demonstrates a method to develop an immunological strategy in coccidiosis control.

Safety evaluation of lasalocid use in Chinese ring-necked pheasants (Phasianus colchicus).

Coccidiosis remains a significant threat to the welfare of game farm-reared pheasants in the United States. Although lasalocid has been demonstrated to be effective against pheasant specific coccidia, information regarding its safety in this species is lacking. The purpose of this study was to gather data on the safety of lasalocid when fed to Chinese ring-necked pheasants at one, two, and three times the recommended high dose of lasalocid used for prevention of coccidiosis in other poultry at three times the normal treatment period. Pheasant chicks (approximately 1 day-old; n = 160) were randomly blocked by sex into four treatment groups and given their respective diets continuously for 6 wk. No significant differences were observed in overall feed consumption, weight gain, feed conversion rates, clinical pathology measurements, or tissue gross and histopathologic evaluations between controls and treatment groups associated with lasalocid administration. Based on the results of this study it appears that lasalocid fed at the recommended rate of 125 ppm is safe in Chinese ring-necked pheasants.

Direct effects of Moringa oleifera Lam (Moringaceae) acetone leaf extract on broiler chickens naturally infected with Eimeria species.

Avian coccidiosis is one of the most important diseases of poultry and it is responsible for a large number of all broiler mortalities worldwide. The control of this disease relies mainly on the use of anticoccidial drugs. However, herbal preparations could be an alternative for the treatment against coccidiosis in chickens. The direct effects of Moringa oleifera acetone extracts on broiler chickens naturally infected with mixed Eimeria species was investigated to determine the relative efficacy of the extracts against coccidiosis in birds. The investigations were carried out in seven groups (ten chickens per group). The birds were given various doses (1.0, 2.0, 3.0, 4.0 and 5.0 g/kg body weight) of acetone extract of leaves of M. toltrazuril (positive control) and untreated (negative control). The extract was evaluated for anticoccidial activity by means of inhibition of oocyst output in faeces, faecal score, weight gain and mortality. Haematological indices were evaluated by standard methods. The group treated with 1.0 g/ kg body weight Moringa oleifera extract produced the least inhibitory effect on oocyst shed in the faeces (96.4%), while the groups treated with 2.0 g/kg, 3.0 g/kg, 4.0 g/kg and 5.0 g/kg body weight of the extract produced 97.4, 98.7, 99.1 and 99.8%, respectively. Body weight gains of infected chickens treated with the extract significantly improved (p < 0.05), and faecal scores were milder. Packed cell volume, haemoglobin concentration and red blood count of the treated birds were significantly (p < 0.05) higher than those of the infected untreated group. Moringa oleifera leaves could find application in the treatment of avian coccidiosis in veterinary practice.

Effects of nicarbazin on the blood glucose and liver glycogen statuses of male broilers.

Nicarbazin (NCZ), an effective anticoccidial widely used by the global broiler industry, is known to produce some side effects in broilers. Recent field observations have suggested that NCZ could be associated with spiking mortality syndrome, a disease of uncertain etiology that is most commonly characterized by hypoglycemia. In turn, 2 trials were conducted to investigate the effects of NCZ on the blood glucose levels and liver glycogen content of Ross × Ross 708 male broilers. In 6 of 12 pens beginning at 1 d of age, NCZ was added to basal broiler diets at a rate of 125 mg/kg, and the other 6 pens were control pens in which birds received salinomycin instead of NCZ, at a rate of 66 mg/kg. Feed and water were provided ad libitum, feed was closely monitored in all pens to avoid shortages, no coccidial challenge was imposed, and room temperature never exceeded 29.4°C. At the end of the second trial, a photoperiod increase from 8L:16D to 24L:0D was imposed in an effort to induce stress due to feed engorgement. In response to NCZ in trial 1, 0 to 28 d feed conversion and relative liver weights on d 21 and 28 were higher, whereas 0 to 28 d cumulative BW gain was lower. In response to NCZ in trial 2, 0 to 13 d feed conversion was higher, whereas 0 to 13 d cumulative BW gain was lower. The added NCZ increased blood glucose on d 13 in trial 2, but did not affect at any time the liver constituents analyzed in both trials. In conclusion, the uninterrupted feeding of NCZ at 125 mg/kg in the starter and grower diets of male Ross × Ross 708 broilers increased feed conversion and reduced BW gain, but despite an increase in relative liver weight on d 21 and 28 posthatch, liver glucose and glycogen concentrations were not affected.

Experimental treatment of Neospora caninum-infected mice with the arylimidamide DB750 and the thiazolide nitazoxanide.

The cationic arylimidamide DB750 and the thiazolide nitazoxanide had been shown earlier to be effective against Neospora caninum tachyzoites in vitro with an IC(50) of 160nM and 4.23µM, respectively. In this study, we have investigated the effects of DB750 and nitazoxanide treatments of experimentally infected Balb/c mice, by applying the drugs either through the oral or the intraperitoneal route. In experiment 1, administration of DB750 (2mg/kg/day) and nitazoxanide (150mg/kg/day) started already 3 days prior to experimental infection of mice with 2×10(6) tachyzoites. Following infection, the drugs were further administrated daily for a period of 2 weeks, either orally or intraperitoneally. Intraperitoneal injection of DB750 was well tolerated by the mice, but treatment with nitazoxanide resulted in death of all mice within 3 days. Upon intraperitoneal application of DB750, the cerebral parasite load was significantly reduced compared to all other groups, while oral application of DB750 and nitazoxanide were not as effective, and resulted in significant weight loss. In experiment 2, mice were infected with 2×10(6) tachyzoites and at 2 weeks post-infection, DB750 (2mg/kg/day) was applied by intraperitoneal injections for 14 days. In the DB750-treated group, only 2 out of 12 mice succumbed to infection, compared to 7 out of 12 mice in the placebo-group. DB750 treatment also resulted in significantly reduced cerebral parasite burden, and reduced numbers of viable tachyzoites. Our data suggest that DB750 exerted its activity also after crossing the blood-brain barrier, and that this class of compounds could be promising for the control of N. caninum-associated disease.

Effects of artemisinin in broiler chickens following chronic oral intake.

Artemisinin has been used for centuries to treat malaria, intestinal tract helminthosis, diarrhea, and used as an antipyretic and sedative agent, but the usage in veterinary medicine is a new field. Recently, it has been used successfully to control experimental poultry coccidiosis. The present study aimed to determine the effects of different doses of artemisinin in broiler chickens with chronic usage. Sixty birds divided into one control and four treatment groups that fed rations mixed with artemisinin at doses of 17, 34, 68, and 136 ppm for 36 days. During the experiment, birds showed no clinical signs except anemia. In microscopic examinations, heart, lung, and spleen had no lesion, but liver, kidney, and brain showed various lesions. Degenerative lesions like intracytoplasmic eosinophilic inclusions were seen in both kidney and liver but fatty change was seen only in liver. There was no relationship between severity of the liver lesions and drug dosage. Central chromatolysis, scattered neuronal necrosis, and mild spongy changes were observed in five regions of the brain that were chosen for sectioning (motor cortex, cerebellar nuclei, midbrain nuclei, and hindbrain nuclei at two separate levels). Severity of lesions in brain was dose-dependent, and cerebral cortex was the most vulnerable area. Haematologic tests showed lower values for hematocrit and red blood cell count dose-dependently. In conclusion, artemisinin is a promising drug for prevention and control of coccidiosis in broiler chickens and its side effects are not too much serious especially at therapeutic doses.

Adverse outcomes associated with the treatment of Toxoplasma infections.

Adverse outcomes associated with the treatment of Toxoplasma gondii infections in patients with various health backgrounds have not been characterized. The aim of this study was to identify the adverse outcomes and adverse events associated with the current clinical treatments of Toxoplama gondii infections using real world data reported to the FDA adverse event reporting system (FAERS). Data submitted to FAERS between 2013 and 2019 was retrieved and analyzed. Reporting odds ratio of death was calculated for the drugs having ≥ 25 reports of adverse outcomes. The adverse event profiles for the same drugs were analyzed and the reporting odds ratio was calculated relative to all other drugs used in the treatment of Toxoplasma infections. There were 503 cases reporting the treatment of Toxoplasma infections in the FAERS database. Death (DE) was the adverse outcome in 102 reports, of which 23 (22.5%) anti-Toxoplasma drugs were listed as the primary suspect drug (PS). Clindamycin (2.04; 1.07-3.90) followed by pyrimethamine (1.53; 0.99-2.36) were the most likely to be associated with death. Adverse events analysis suggest that sulfonamides formulations may have a less favorable safety profile. Our study represents the first real-world analysis of adverse outcomes and events associated with the treatment of Toxoplasma infections. Our findings support the need to better understand the current first-line agents for Toxoplasma infections, in addition to underscoring the need to identify safer regimens.

[Accidental feeding of the coccidiostat nicarbazin in layer breeder flocks - A case report]. / Versehentliche Fütterung von Legehennen-Elterntier-Herden mit dem Kokzidiostatikum Nicarbazin.

Following the accidental feeding of a compound feed containing the coccidiostat nicarbacin in layer breeder flocks (Lohmann Brown Classic), the birds displayed distinct clinical signs within a few hours. Mortality increased during the following 5 days, whereas laying performance and hatching rate of eggs during this period decreased markedly. Egg shell discoloration was observed as early as during the first day. As a consequence, an association between feeding of the coccidiostat nicarbacin and the observed symptoms was assumed. Recent studies indicate that Nicarbacin reduces the activity of aminolevulinic acid synthase type 1 (ALAS 1), which is responsible for the synthesis of protoporphyrin IX in the shell gland as main compound of brown egg shells. Reduced laying performance and increased mortality was likely due to nicarbacin-induced deregulated body temperature homeostasis and concomitant imbalances in acid-base status of the animals. The case reveals that the accidental feeding of nicarbacin to non-target animals such as laying hens and their parents may result in acute clinical symptoms. This highlights the necessity of appropriate care in handling feed additives and their premixes for specific non-target animals and should sensitize farmers and veterinarians.

Safety pharmacology assessment of Ethanamizuril, a novel triazines coccidiostat.

In the current study, to support the safety pharmacology assessment of Ethanamizuril as a new potent anticoccidial agent of triazine compounds, the effects of Ethanamizuril on the central nervous system, cardiovascular system and respiratory system were investigated. Using locomotor activity test, climbing behavior test and nembutal subthreshold hypnotic test at each time point after oral administration of Ethanamizuril to mice, the effects on the central nervous system were evaluated. An assessment of Ethanamizuril effects on the cardiovascular and respiratory system were performed by the use of a telemetry system in conscious beagle dogs. The results showed that the treatment of Ethanamizuril had no effects on motor activity, behavioral changes, coordination, and sensory/motor reflex responses in mice. There were also no changes in heart rate, blood pressure, and electrocardiogram at all doses and each time points in beagle dogs. Our data suggested that Ethanamizuril showed no adverse effects on the central nervous system, cardiovascular system, and respiratory system.

Susceptibility of chicken Lactobacillus bacteria to coccidiostats.

The aim of this study was to determine the susceptibility of Lactobacillus bacteria to selected coccidiostats. Seventy-five Lactobacillus isolates obtained from chickens were classified by MALDI-TOF mass spectrometry and 16S rDNA restriction analysis into seven species, among which L. salivarius (33%) and L. johnsonii (24%) were dominant. Susceptibility of lactobacilli to coccidiostats was determined by broth microdilution method. The ranges of minimum inhibitory concentrations (MICs) were 0.5-≥128 µg/ml for monensin, 0.125-8 µg/ml for salinomycin, ≤0.03-2 µg/ml for lasalocid A, and 4-16 µg/ml for robenidine. Coccidiostats in low concentrations inhibited in vitro growth of most lactobacilli and therefore there is a high probability that administration of this drugs to chickens would reduce the number of lactobacilli in the gut.

Effects on health, performance, and tissue residues of the ionophore antibiotic salinomycin in finishing broilers (21 to 38 d).

A study was conducted to evaluate the effects of feeding salinomycin at the recommended prophylactic level, and at 2 and 3 times this level, to finishing male broilers (d 21 to 38). Four treatment groups were given the experimental diets containing 0, 60, 120, or 180 parts per million (ppm) salinomycin from d 21 to 38. Performance, relative organ weights, selected serum enzymes, and salinomycin residues in liver, muscle, and serum were determined. Salinomycin supplementation had no effect on body weight, feed intake, or feed conversion, and caused no overt signs of toxicity. After a week of being fed the salinomycin diets, the serum activity of aspartate aminotransferase was significantly increased in chickens fed 180 ppm compared with controls. These birds also showed microscopic lesions in breast and thigh muscles, but not in cardiac muscle. Salinomycin residues were not detected by high-performance liquid chromatography coupled to tandem mass spectrometry in liver or muscle samples from the birds fed 0, 60, or 120 ppm salinomycin. However, chickens fed 180 ppm salinomycin had detectable levels in liver and muscle above the maximum residue level of 5 µg/kg established by the European Union. All birds fed salinomycin had salinomycin in their sera with levels ranging from N.D. (not detected) in the controls to 24.4 ± 7.9, 61.4 ± 18.9, and 94.5 ± 9.1 µg/L for salinomycin dietary levels of 60, 120, and 180 ppm, respectively. Serum salinomycin concentration was linearly related with salinomycin content in feed (y = 0.584x - 10, r2 = 0.999). The results showed that even at 3 times the prophylactic level, salinomycin does not induce clinical toxicosis or mortality. No salinomycin residues were found in edible tissues at the recommended dietary level or at 2 times this level. However, salinomycin was detected in serum regardless of the dietary level. A simple method for salinomycin determination in serum is described which can be used as a marker of exposure and/or to predict levels in the diet.

Treatment of cryptosporidiosis in captive green iguanas (Iguana iguana).

There are no standard guidelines for the treatment of cryptosporidiosis in reptiles. The aim of this study was to evaluate the efficacy of two cryptosporidiosis therapies in captive green iguanas. Eight green iguanas aged 2-6 years, including 6 (1 ♂ and 5 ♀) animals with chronic diarrhea, received treatment for cryptosporidiosis. The presence of Cryptosporidium sp. oocysts was determined in 8 iguanas (100%), Isospora sp. oocysts were detected in 3 animals (37.5%), and Oxyuridae eggs were observed in 5 iguanas (62.5%). The animals were divided into two therapeutic groups (A and B). Group A iguanas were administered halofuginone (Halocur, 0,50 mg/ml Intervet Productions S.A., France) at a dose of 110 mg/kg body weight (BW) every 7 days for 5 weeks. Group B animals were administered sulfadiazine and trimethoprim (Norodine Vet Oral Paste sulfadiazine 288,3 mg/g, trimethoprim 58 mg/g, ScanVet Animal Health A/S, Denmark) at 75 mg/kg BW per os every 5 days for 5 weeks and spiramycin and metronidazole (Stomorgyl, spiramycin 1500000 IU, metronidazole 250 mg, Merial, France) at 200 mg/kg BW every 5 days for 5 weeks. Both groups received hyperimmune bovine colostrum and subcutaneous fluids. Before treatment, the average number of Cryptosporidium sp. oocysts in 1 g of feces was determined at 1.71 * 105 (±313,262.44) in group A and 1.56 * 105 (±262,908.53) in group B; the average number of Isospora sp. oocysts was determined at 3.53 * 103 (±1747.38), and the average number of Oxyuridae eggs was determined at 810 (±496.74). Blood tests were performed once before treatment. The results of blood morphology and biochemistry tests before treatment revealed leukocytosis with a significant increase in heterophile and monocyte counts in all animals. Dehydration, elevated hematocrit values and low levels of Na+, Ca2+, PO4- and Cl- ions were observed in 6 iguanas. Two iguanas died during treatment. The gross necropsy revealed acute inflammation of gastric and duodenal mucosa, mucosal ecchymoses in the gastrointestinal tract, hepatomegaly and liver congestion, cholecystitis, enlarged kidneys and renal edema and congestion, cystitis, and an absence of fat bodies. Parasites were not detected in any developmental form after 40 days of therapy and during an monthly 18-month follow-up period. Effective treatment of cryptosporidiosis in reptiles minimizes the adverse consequences of disease, improves the animals' well-being and decreases euthanasia rates.

Current research, regulation, risk, analytical methods and monitoring results for nicarbazin in chicken meat: A perspective review.

This review presents up-to-date information about current research on nicarbazin, one of the most used anticoccidials in poultry production. The focus is to elucidate regulation concerning nicarbazin, limits for its residues in food, how maximum residue limits in different countries are calculated regarding edible chicken tissues and the possible implications in human health. Analytical methods to extract and quantify this residue, expressed as dinitrocarbanilide (DNC) are presented and discussed, including qualitative screening and quantitative/confirmatory analytical methods. Monitoring results and occurrence of DNC residues in chicken meat are discussed. Additionally, the causes of eventual chicken meat contamination and possible solutions to reduce or eliminate DNC residue in tissues are also presented. The paper concludes with perspectives, the current state of DNC residue analysis and suggestions for future research, especially considering the gap in the study of residue recycling effect due to continuous chicken litter use.

The physiological response of broiler chickens to the dietary supplementation of the bacteriocin nisin and ionophore coccidiostats.

The aim of this study was to investigate the effect of dietary supplementation with nisin alone or in combination with salinomycin or monensin on broiler chickens in terms of growth performance, selected blood parameters, digestive enzyme activity, apparent nutrient digestibility, and tibiotarsus mineralization, as well as selected gastrointestinal tract (GIT) organ weights, intestinal length, and central immune organ weights. Two independent experiments, each including 400 one-day-old female Ross 308 chicks differing in ionophore coccidiostats, i.e., salinomycin and monensin supplementation, were conducted. The following treatments were applied: experiment 1: NA-no additives, SAL-salinomycin (60 mg/kg diet), NIS-nisin (2,700 IU/kg diet), SAL+NIS-salinomycin (60 mg/kg diet) and nisin (2,700 IU/kg diet); experiment 2: NA-no additives, MON-monensin (100 mg/kg diet), NIS-nisin (2,700 IU/kg diet) and MON+NIS-monensin (100 mg/kg diet) and nisin (2,700 IU/kg diet). The addition of nisin with or without ionophores to the birds' diet improved broiler growth performance in terms of BWG and FCR (days 1 to 14) and BWG and FI (15 to 35 d; 1 to 35 d). Salinomycin showed effects similar to those of nisin influence on growth performance (1 to 35 d), while monensin supplementation resulted in lower BWG. Moreover, no additive effect between nisin and ionophores was observed. Nisin and salinomycin had no influence on the serum concentration of selected hormones and other blood biochemical parameters except glucose, which was reduced by nisin. A decrease in lipase activity was observed during nisin and salinomycin supplementation, while the apparent ileal digestibility of fat was not affected. However, the digestibility of crude protein increased with nisin administration. Additionally, the effects of nisin on decreasing the weight and length of GIT segments were observed. Supplementation with nisin and monensin was not associated with a negative impact on tibiotarsus mineralization and the immune organ index. This study suggests that nisin may be used in broiler nutrition as a growth promotor, with no negative influence on the bird's metabolism or immune status.

Performance and anticoccidial effects of nicarbazin-fed broilers reared at standard or reduced environmental temperatures.

A series of 4 floor pen studies was conducted to evaluate the effects of environmental temperature modification on nicarbazin (NIC) responses in broiler chickens raised to 28 d of age. Birds were reared at either standard temperatures (recommended by the primary breeder for ages zero to 28 d) or at 3°C below this level. From placement to 28 d, birds were provided feeds containing zero, 100, or 125 ppm NIC, comprising a 2 × 3 factorial arrangement in each test. Two of the trials were conducted in the presence of an imposed coccidial challenge and 2 were conducted in healthy animals. At 18 and 28 d of age, performance was recorded; cloacal temperatures were measured at 7, 14, 21, and 26 days. Mortality data were collected daily and coccidial lesions were scored at 6 d post challenge. Results of these studies revealed that NIC improved coccidial lesion scores regardless of environmental temperature. In the absence of coccidial challenge, NIC depressed performance, but reductions in environmental temperature diminished the magnitude of these responses. Under conditions of coccidial challenge, NIC significantly improved body weight gains in both temperature environments. Compared to standard temperature conditions, lower environmental temperatures exerted a positive effect on feed conversion rates of NIC-fed broilers. Birds reared in the low temperature environment exhibited lower cloacal temperatures than standard environment groups throughout the test period. Irrespective of coccidial challenge, lower environmental temperatures significantly reduced nicarbazin mortality compared to standard temperature groups, resulting in a significant nicarbazin x temperature interaction. This finding indicates that temperature modification is a practical method for minimizing mortality over the course of 28-day nicarbazin usage.

[Results of therapy in ocular toxoplasmosis. Comparison of various forms of therapy]. / Ergebnisse der Therapie bei okulärer Toxoplasmose. Ein Vergleich unterschiedlicher Therapieformen.

We performed a retrospective non-random study to evaluate the effectiveness of different therapeutical concepts in the treatment of retinal toxoplasmosis. Visual acuity after therapy and at the end of the observation period as well as the recurrence frequency were used to determine the success of treatment. The protocols of 75 patients treated for retinal toxoplasmosis at the University of Hamburg were evaluated for this study. The mean observation period was 220 weeks with a standard deviation of 110 weeks. Concerning the visual outcome, a therapeutic effect was statistically shown for monotherapy with antibiotics and for their combination with corticosteroids. Steroid therapy was demonstrated to be helpful, especially in cases of extramacular localization of fundus lesions. This was probably caused by steroid-induced improvement of vitreous infiltration. As for the different antibiotics used, the combination of clindamycin with sulfmethoxydiazine and/or pyrimethamine showed the best results. Monotherapy with clindamycine alone had statistically no effect on the final visual outcome. The relapse frequency was not influenced by any therapeutic concept used. According to these results, a combination of clindamycine and pyrimethamine should be the therapy of choice for treatment of retinal toxoplasmosis.

Production and egg-quality responses of White Leghorn layers to anticoccidial agents.

Two studies were conducted to determine the effects of anticoccidial agents on the production and reproduction of White Leghorns. In Experiment 1, nicarbazin (NCZ) was fed at 0, 20, 50, and 100 ppm. Hen-day egg production, egg weight, the egg-yolk DNC (4-4'-dinitrocarbanilide) level, and egg-yolk mottling were affected by the treatments. When response was evidenced, the relationship between those variables and the level of NCZ was basically linear. Decreased egg production occurred from Days 5 and 6 of the treatment through Days 1 and 2 of withdrawal. On Days 9 and 10 of treatment, the control hens peaked at 92% hen-day production, while hens fed 20, 50, and 100 ppm of NCZ peaked late--at 90, 82, and 80%, respectively. Compared to the controls, egg weight was reduced linearly as the level of dietary NCZ increased. The egg-yolk DNC level increased from Days 3 and 4 of treatment through Days 9 and 10 of withdrawal. Egg yolk mottling generally increased along with the level and duration of feeding NCZ. If the NCZ was mistakenly fed to White Leghorn layers, ill effects would be alleviated within 10 days after drug withdrawal. In Experiment 2, halofuginone (3 ppm), maduramicin (5 ppm), monensin (100 ppm), narasin (70 ppm), nicarbazin (125 ppm), robenidine (33 ppm), and salinomycin (60 ppm) were fed to White Leghorn hens at the levels specified in parentheses. Nicarbazin reduced egg production, depressed egg weight, reduced shell thickness, and caused egg-yolk mottling; but internal egg quality, as measured by Haugh Units, was unaffected. Halofuginone, maduramicin, monensin, narasin, robenidine, and salinomycin did not have a meaningful effect on the variables measured when fed to White Leghorn layers.

Increased skin tearing in broilers and reduced collagen synthesis in skin in vivo and in vitro in response to the coccidiostat halofuginone.

In vivo and in vitro experiments were conducted in an effort to elucidate the mechanism of suppression by halofuginone of skin strength in broilers. In the in vivo study, halofuginone was included at concentrations of 0, 1.5, 3, and 6 mg/kg of diet, corresponding to 0, 50, 100, and 200%, respectively, of the amount recommended for use as a coccidiostat. Each dietary treatment was given to 260 female broiler day-old chickens. Skin tearing was evaluated at the processing plant. Skin collagen and Kjeldahl-nitrogen were determined chemically. At the age of 7 wk, BW and feed efficiency were affected only in birds consuming the diet containing the highest concentration of the drug. Skin tearing increased but skin collagen concentration decreased in a dose-dependent manner. Fibroblasts were obtained by collagenase digestion from chicken skin and cultured. The cultured cells were incubated with various concentrations of halofuginone, monensin, and nicarbazin, and [3H]proline incorporation was evaluated in collagenase-digestible (representing mostly collagen) and nondigestible proteins exported by the cells into the medium. Halofuginone, at a concentration as low as 10(-11) M, inhibited incorporation of [3H]proline into collagenase-digestible proteins, but did not affect incorporation of [3H]proline into collagenase-nondigestible proteins. Even at concentrations as high as 10(-9) M, neither monensin nor nicarbazin affected collagenase-digestible proteins. The in vitro results suggest that halofuginone specifically inhibits collagen synthesis by skin fibroblasts. Results of both in vivo and in vitro trials suggest that the increase of skin tearing during processing, induced by halofuginone, is caused by direct suppression of skin collagen synthesis.

Mitigating the effects of halofuginone on skin strength by feeding L-proline to broiler chickens.

Two experiments were conducted to determine whether supplemental levels of L-proline in the diets of broiler chickens would mitigate the skin weakening effect caused by continuous feeding of the anticoccidial halofuginone. In Experiment 1, tensile strength and collagen levels in thigh apteria skin were determined at 21 and 42 d of age in male broilers fed 0, .5, and 1% L-proline with either halofuginone (3 mg/kg) or salinomycin (61 mg/kg). In Experiment 2, the same measurements were made on female broilers receiving diets containing halofuginone and supplemented with 0, .5, or 1% L-proline, 1% L-proline through 21 d of age, or 1% L-glutamic acid through 21 d of age, or a diet containing high L-proline feedstuffs (corn gluten meal and ring dried blood meal). In Experiment 1, dermis thickness of thigh apteria was measured in the males at Day 21. Skin strength was increased in male and female broilers fed halofuginone with addition of .5 and 1% L-proline, respectively, at 21 and 42 d of age. Continuous incorporation of synthetic L-proline into diets was shown to improve skin strength in females, whereas diets formulated to contain high levels of L-proline from feedstuffs, 21-d feeding of L-proline, or L-glutamic acid did not increase skin strength.