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1.
PLoS One ; 19(7): e0306889, 2024.
Article in English | MEDLINE | ID: mdl-38995898

ABSTRACT

Even when pain control is implemented, calves may experience pain for days after hot-iron disbudding. Whether calves seek pain relief post-disbudding offers a novel approach to assessing pain in these animals. By employing an approach-aversion paradigm, we explored the ability of cold therapy to provide immediate pain relief in disbudded calves. Calves were habituated to the manual placement of a cool or ambient pack on their forehead for a short duration simultaneous to milk reward consumption, prior to disbudding. Calves were then disbudded under local anaesthesia (procaine) and analgesia (meloxicam), and responses to the packs were observed over subsequent days. Individual calves were consistently exposed to either cool or ambient packs in different halves of a two-sided experimental pen, allowing for the testing of approach-aversion and conditioned place preference. We found calves approached milk rewards quicker and maintained contact for longer when receiving cold therapy compared to the ambient control. However, calves did not display any conditioned preference for the pen where they received the cool pack. These results add to the growing evidence of lasting pain following disbudding procedures and suggests that cold therapy provides some form of pain relief post-disbudding. Future studies should seek other ways to use cold therapy post-disbudding to reduce aversiveness and human involvement.


Subject(s)
Horns , Pain Management , Animals , Cattle , Horns/surgery , Pain Management/methods , Cryotherapy/methods , Cryotherapy/veterinary , Pain , Female , Cold Temperature , Dairying
2.
Sci Rep ; 14(1): 9684, 2024 04 27.
Article in English | MEDLINE | ID: mdl-38678149

ABSTRACT

Stalls or crates are a very common type of housing used on pig farms that restrict an animal's movement. How this confinement impacts the animal's affective states is seldom investigated. We conducted a preference test over 7 days where trios of gilts (n = 10 trios, 27.4 ± 1.5 weeks old) had free access between individual self-locking stalls (~ 1.2 m2) and a shared open area allowing 2.8 m2/animal (71% of total area). Gilts had access to ad libitum feed and water both inside the crates and in the open area. After 7 days, personality traits of the animals were assessed with open field (OF) and novel object (NO) tests. Principal Component Analysis (PCA) yielded two main components, which we defined as Passivity and Engagement. The median time spent outside the crate was 95.2% as 21/29 of the gilts exhibited a significant preference for pen over crate during the 7-day trial (p < 0.05). Passivity had no relationship with time spent in the open area, but engagement during OF/NO was associated with less use of the open area (OR = 0.39, 95CI = [0.25, 0.60]). Interestingly, gilts were likely to spend less time in the open area at nighttime compared to daytime (Odds Ratio = 0.49, 95CI = [0.40, 0.60]), as well as experimental days passed (OR = 0.70, 95CI = [0.66, 0.73]). During the first daytime and nighttime, 1/29 and 2/29 animals preferred the crate respectively, whereas by the last daytime and nighttime 5 and 9 gilts preferred the crate respectively (p < 0.05). While both intrinsic (personality) and extrinsic (time of day, experimental day) factors appear to influence the gilt's housing preferences, most gilts significantly prefer an open area to a crate when free access is provided between the two. A smaller subpopulation of animals developed a preference for stalls but still utilize both the stall and the pen throughout the day.


Subject(s)
Behavior, Animal , Housing, Animal , Animals , Female , Swine , Behavior, Animal/physiology , Animal Husbandry/methods , Animal Welfare
3.
JDS Commun ; 4(6): 479-483, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38045900

ABSTRACT

On most dairy farms, calves are housed individually until weaning. However, depriving calves of an early social environment impairs behavioral development. We studied the effect of early-life social housing on calves' competitive skills. In this study, Holstein heifers were pseudorandomly assigned to either individual housing (n = 9) or pair housing (with a nonfocal companion, n = 9) at the age of 11 d. After 14 d of housing treatment, calves underwent a competition test for milk access against a group-reared calf; consisting of 2 test sessions per day for 5 d (session duration: 74.42 ± 2.29 s; mean ± standard error). Pair-housed calves performed better than individually housed calves: throughout the competition days, individually housed calves increased their latency to approach the milk bottle and decreased their time spent drinking in contrast to pair-housed calves, which exhibited stable latencies to reach the milk bottle and increased their time drinking. To control for the influence of personality on their competitive abilities, all calves were subjected to personality tests assessing boldness before being exposed to the housing treatment. Our findings indicate that calves assessed as bolder during the pretreatment personality test tended to approach the milk bottle faster. Our results provide additional evidence of the beneficial effects of social housing on dairy calves' behavioral development.

4.
Front Vet Sci ; 10: 1251070, 2023.
Article in English | MEDLINE | ID: mdl-38033647

ABSTRACT

Cognitive approaches are increasingly used to assess animal welfare, but no systematic review has been conducted on pigs despite their cognitive capacities. Our aims were two-fold: first, to assess the popularity and heterogeneity of this approach by quantifying the different cognitive tasks used and welfare interventions studied. The second was to assess how often results from cognitive tasks supported treatment effects. The search yielded 36 studies that met our criteria. Eleven different cognitive tasks were applied (three most common: judgment bias, learned approach/aversion, and holeboard). Welfare interventions investigated were also diverse: the impact of 19 other different events/conditions/states were reported (most common: housing enrichment). We defined "supportive" as the observation of a significant difference between treatment groups consistent with an author's expectation or hypothesis. Supportive findings were reported in 44% of papers. Interventions yielded no significant difference in 33% of studies. In another 21% of reports, outcomes were mixed and a single study refuted the author's predictions. When considering specific cognitive tasks, authors' predictions of welfare differences were supported most often when using learned approach/aversion (55% of these studies). Similar supportive results were observed less commonly (40% each) when using judgment bias and holeboard tests. Analysis of additional concomitant measures of welfare (health, physiology or behavior) revealed that behavioral measures were most frequently supportive of author's expectations (41%) as well as often matching the actual outcomes of these cognitive tasks (47%). This systematic review highlights the growing popularity of cognitive tasks as measures of pig welfare. However, overall rates of supportive results, i.e., changes in performance on cognitive tasks due to welfare interventions, have been limited so far, even for the most employed task, judgment bias. The numerous different combinations of experimental paradigms and welfare interventions reported in the literature creates challenges for a critical meta-analysis of the field especially in evaluating the efficiency of specific cognitive tasks in assessing animal welfare. This work also highlights important knowledge gaps in the use of cognitive tasks that will require both further validation as well as novel innovation to ensure that their potential is fully realized in the measurement of pig welfare.

5.
Sci Rep ; 13(1): 15403, 2023 09 16.
Article in English | MEDLINE | ID: mdl-37717122

ABSTRACT

Negative emotional states are known to interact, potentially aggravating one another. In this study, we used a well validated paradigm (successive negative contrast, SNC) to determine if pain from a common procedure (disbudding) influences responses to a reward downshift. Holstein calves (n = 30) were trained to approach a 0.5 L milk reward. Latency to approach, number of vocalisations and pressure applied on the bottle were recorded during training. To assess how pain affected responses to reward downshift, calves were randomly assigned to one of three treatments before the downshift. Two groups were disbudded and provided the 'gold standard' of pain mitigation: intraoperative local anesthesia and analgesia. One of these disbudded groups was then provided supplemental analgesic before testing. The third group was sham disbudded. All calves were then subjected to the reward downshift by reducing the milk reward to just 0.1 L. Interactions were detected between test session and daily trials on pressure applied for the Disbudded group (estimate ± SEM: 0.08 ± 0.05), and on vocalisations for the Sham (0.3 ± 0.1) and Disbudding + Analgesia (0.4 ± 0.1) groups. Our results indicate that SNC is a promising paradigm for measuring negative affect in calves and suggests that pain potentially affects the response to a reward downshift.


Subject(s)
Pain , Reward , Animals , Cattle , Analgesia , Pain/psychology , Pain/veterinary , Pain Management
6.
Sci Rep ; 13(1): 5679, 2023 04 07.
Article in English | MEDLINE | ID: mdl-37029265

ABSTRACT

In humans, the 'peak-end' rule states that recollection of an experience is most often influenced by the peak (the most intense moment) and end of the experience. We investigated whether calves followed the peak-end rule in their memory of a painful procedure: disbudding. As proxies for retrospective and 'real-time' reports of pain, we used conditioned place aversion, and reflex pain behaviours. In two separate trials, calves were subjected to two disbudding conditioning sessions (one horn per treatment), acting as their own control. In the first trial, calves (n = 22) were disbudded and remained in a pen for 4 h, and disbudded and left in another pen for 4 h with an additional 2 h following an analgesic treatment. In the second trial, calves (n = 22) were disbudded and left in pens for 6 h during both treatments, receiving the analgesic at either 2 h or 4 h after disbudding. Calves were then tested for place aversion. For both trials we did not observe a preference for the pens where calves received analgesic treatment towards the end of the session. We did not find an association between aversion and the sum, peak or end of pain behaviours. Results are not consistent with a peak-end effect in calves' memory of pain.


Subject(s)
Horns , Transcutaneous Electric Nerve Stimulation , Animals , Cattle , Animal Husbandry/methods , Pain/veterinary , Retrospective Studies
7.
JDS Commun ; 3(6): 421-425, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36465506

ABSTRACT

Male cattle reared for beef are typically castrated. Male calves born on dairy farms are increasingly reared for beef, so a better understanding of how to humanely perform this procedure in dairy systems is now required. We studied the short-term affective responses of dairy calves to castration using a conditioned place aversion paradigm. Young Holstein bulls (16 d old, n = 30) were castrated by either rubber ring (n = 15) or surgery (n = 15), and then kept in a visually distinctive recovery pen for 6 h after the procedure. Calves acted as their own control and were sham castrated and allowed to recover for 6 h in another visually distinctive pen. During both castration and sham procedures, calves received a sedative (xylazine, 0.2 mg/kg), local anesthetic (lidocaine, 5 mL), and a nonsteroidal anti-inflammatory (meloxicam, 0.5 mg/kg). After exposure to both treatments (castration and sham), calves were tested for place aversion by providing free access to the 2 pens where they experienced the different treatments. Calves were tested for aversion 48, 72, and 96 h after their last treatment. We recorded how much time they spent in each pen and where they chose to rest. We did not find differences in time spent resting or resting location, suggesting that calves did not form a more negative memory of castration in comparison to the sham procedure. The lack of treatment effects may be due to features of our testing paradigm, including effective multimodal pain control during the 6-h conditioning period and limiting testing to the first days after the procedure.

8.
JDS Commun ; 3(1): 44-48, 2022 Jan.
Article in English | MEDLINE | ID: mdl-36340682

ABSTRACT

Most dairy calves are housed individually in the first weeks and sometimes months of their lives. Lack of social interaction can negatively impact feed intake, social skills, coping abilities, and cognitive performance, but the motivation of calves to seek companionship has seldom been investigated. In this study, 10 Holstein bull calves (Bos taurus; averaging 5.4 ± 2.6 d old upon entering the study) were housed individually in a central home pen with access to one pen on either side, each connected by a push gate. One side pen housed another calf of similar age and the same sex, and the second was otherwise identical in size and resources (feed and water) but without a social companion. Each time the test calf pushed open the gate to access a side pen, he would be left in it until the next feeding (approximately 0800 and 1600 h), at which time he was returned to the central home pen. After each successful pushing event, additional weight was added to the gate (initially a small amount, then incrementally higher). All calves but one pushed for the first time on d 1 of enrollment (within 9.4 ± 14.8 min of experimental start); the remaining calf pushed on d 3 of the test. Each calf was tested for 15 d and we recorded the maximum weight pushed for both side pens. Calves pushed a higher maximum weight (and pushed more frequently) for access to the pen with a social partner compared with the empty pen. We conclude that calves are socially motivated, even at a young age, and that calves can benefit from access to social contact.

9.
J Dairy Sci ; 103(12): 11653-11658, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33069402

ABSTRACT

Cauterization by hot iron and application of caustic paste are 2 common methods of disbudding calves. In this study, we compared the affective experience of these 2 procedures on young dairy calves using conditioned place aversion. Male dairy calves (n = 14; 7 ± 2 d old) were disbudded by both thermal and chemical methods (1 horn bud at a time, 48 h apart). Calves received treatments in pens made visually distinct with either red squares or blue triangles on the walls. Calves were restricted to these treatment pens for 6 h following disbudding. For all treatments, calves received a sedative (xylazine, 0.2 mg/kg), local anesthetic (lidocaine, 5 mL), and analgesic (meloxicam, 0.5 mg/kg). Calves were then tested for conditioned place aversion at 48, 72, and 96 h after their last treatment. During tests, calves were placed in a neutral pen connected to both treatment pens where they had previously been disbudded. Time spent in each treatment pen was recorded until calves chose to lie down for 1 min (latency to lie down: 31.0 ± 8.6 min). During the first test (48 h after last disbudding), calves spent more time in the pen associated with hot-iron disbudding compared with what would be expected by chance (intercept: 73.5%, 95% CI: 56.5, 90.5) and fewer calves lay down in the caustic paste pen than in the hot-iron pen (3 vs. 10 lying events). No evidence of preference for the hot-iron pen was found in the following test sessions (72 and 96 h since last disbudding). These results suggest that calves initially remember caustic paste disbudding as a more negative experience than hot-iron disbudding, even with the use of sedation, local anesthesia, and analgesia.


Subject(s)
Caustics/pharmacology , Cautery/veterinary , Conditioning, Psychological , Horns/drug effects , Horns/surgery , Anesthesia, Local/veterinary , Anesthetics, Local/pharmacology , Animals , Cattle , Hypnotics and Sedatives/pharmacology , Iron , Lidocaine/pharmacology , Male , Meloxicam/pharmacology , Pain Management/veterinary , Xylazine/pharmacology
10.
PLoS One ; 15(5): e0232897, 2020.
Article in English | MEDLINE | ID: mdl-32407340

ABSTRACT

Despite scientific interest in animal empathy, and growing public concern for farm animal welfare, the empathic abilities of farm animals remain under researched. In this study, we investigated empathic responses of young Holstein dairy calves to conspecifics recovering from hot-iron disbudding, a painful procedure common on dairy farms. A combination of social approach and place conditioning was used. First, 'observer' calves witnessed two 'demonstrator' calves recover from either a painful procedure (hot-iron disbudding and sedation) or a sham procedure (sedation alone) in distinct pens. Observer calves spent more time in proximity and paid more attention to calves recovering from the painful procedure compared to sham calves (proximity: 59.6 ± 4.3%; attention: 54.3 ± 1.5%). Observers were then tested for conditioned place aversion (in the absence of demonstrators) at 48h, 72h and 96h after the second demonstration; observers tended to avoid the pen associated with conspecific pain during the second of the three tests, spending 34.8 ± 9.6% of their time in this pen. No strong evidence of pain empathy was found, but our tentative results encourage further research on empathy in animals.


Subject(s)
Animal Husbandry/methods , Behavior, Animal , Cautery/veterinary , Empathy/physiology , Horns/surgery , Pain, Postoperative/psychology , Pain, Postoperative/veterinary , Animals , Cattle , Female
11.
Biol Lett ; 15(10): 20190642, 2019 10 31.
Article in English | MEDLINE | ID: mdl-31662066

ABSTRACT

Pain in animals is typically assessed using reflexive and physiological responses. These measures allow inferences regarding nociception but provide little basis for conclusions about the affective component of pain (i.e. how negatively the experience is perceived). Calves routinely undergo painful procedures on commercial farms, including hot-iron disbudding, providing a convenient model to study pain in animals. The aim of this study was to investigate the affective component of post-procedural pain due to hot-iron disbudding, using conditioned place aversion. Calves (n = 31) were subjected to two procedures (one bud at a time): one without post-procedural pain control and the other with the use of a nonsteroidal anti-inflammatory drug (either meloxicam (n = 16) or ketoprofen (n = 15)). All procedures included the use of local anaesthesia (lidocaine). Place conditioning was tested 2 days after the last treatment by allowing calves to freely roam between the pens where they had previously been disbudded. Calves spent more time, and lay down more frequently, in the pen where they received meloxicam compared with the pen where they only received a local block. Surprisingly, calves avoided the pen where they received ketoprofen compared with the control treatment pen. We hypothesize that the shorter duration of action of ketoprofen resulted in increasing pain at the end of the conditioning period, explaining the increased aversion to this treatment. These results illustrate the value of place conditioning paradigms to assess the affective component of pain in animals, and suggest that the animal's evaluation of painful events depends upon the time course of when the pain is experienced.


Subject(s)
Horns , Anesthesia, Local , Animals , Cattle , Pain
12.
J Dairy Sci ; 102(11): 10677-10694, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31477285

ABSTRACT

Affective states, which refer to feelings or emotions, are a key component of animal welfare, but these are also difficult to assess. Drawing upon a body of theoretical and applied work, we critically review the scientific literature on the assessment of affective states in animals, drawing examples where possible from research on dairy cattle, and highlighting the strengths and weaknesses of scientific methods used to assess affective states in animals. We adopt the "valence/arousal" framework, describing affect as a 2-dimensional space (with valence referring to whether an experience is positive or negative, and arousal referring to the intensity of the experience). We conclude that spontaneous physiological and behavioral responses typically reflect arousal, whereas learned responses can be valuable when investigating valence. We also conclude that the assessment of affective states can be furthered using mood assessments and that the use of drug treatments with known emotional effects in humans can be helpful in the assessment of specific affective states in animals.


Subject(s)
Cattle/psychology , Affect , Animal Welfare , Animals , Arousal , Emotions
13.
Sci Rep ; 9(1): 5344, 2019 03 29.
Article in English | MEDLINE | ID: mdl-30926934

ABSTRACT

Dairy calves are routinely disbudded by cauterization with a hot iron. To mitigate the intra-operative and initial post-operative pain associated with this procedure some farmers provide calves general and local anesthetics, but it is unknown if the procedure remains aversive. We used a place-conditioning paradigm to assess aversion caused by hot-iron cautery with a local anesthetic compared to a sham procedure. A test area was divided into three equally sized pens: two 'treatment' pens with distinct visual cues were connected by a central 'neutral' pen. Each calf went through the disbudding procedure and a 6-h recovery period in one treatment pen and the control procedure in the other treatment pen. In three tests (48, 72 and 96 h after the second treatment), calves could freely roam among the pens until they chose to lie down, ending the session. Calves spent less time in either of the treatment pens compared to the central pen. When only comparing the two treatment pen, calves spent less time in the disbudding pen, especially during the first test. Calves were also less likely to lie down in the pen associated with the disbudding procedure. We conclude that even with the use of a local anesthetic, hot-iron disbudding is salient and aversive for calves, indicating the need to refine or avoid the procedure.


Subject(s)
Aversive Therapy/methods , Horns , Animals , Cattle , Pain, Postoperative/prevention & control
14.
Sci Rep ; 8(1): 9443, 2018 06 21.
Article in English | MEDLINE | ID: mdl-29930261

ABSTRACT

We assessed aversion to injections using an avoidance-learning paradigm. Holstein calves (n = 24) were randomly assigned to one of four routes of administration for 0.5 ml of saline: intramuscular (IM), intranasal (IN), subcutaneous (SC) and a null control. Calves were first trained to approach a milk reward of 1 L. Once the latency to approach the reward was consistent, calves received their assigned treatment when approaching the bottle. For the first 3 treatment sessions calves received a 1 L milk reward. This reward was then reduced to 500 mL, and then to 250 mL, and finally to 0 mL, each for 3 sessions. Compared to control calves, calves receiving the intramuscular injections showed a longer latency to approach the milk reward, but only when the milk reward was 0.25 L (P = 0.05) and 0 L (P < 0.01). Calves receiving the intranasal injections showed longer latencies relative to the controls only for the 0 L reward (P = 0.01). Calves receiving the subcutaneous injections did not differ from controls for any of the milk rewards (P > 0.2). We conclude that IM injections are aversive and that SC and IN routes are a refinement to be considered when feasible.


Subject(s)
Administration, Intranasal/adverse effects , Avoidance Learning , Injections, Intramuscular/adverse effects , Injections, Subcutaneous/adverse effects , Administration, Intranasal/veterinary , Animals , Cattle , Injections, Intramuscular/veterinary , Injections, Subcutaneous/veterinary , Random Allocation , Reaction Time , Reward
15.
J Hypertens ; 28(9): 1928-34, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20577127

ABSTRACT

BACKGROUND: We studied the effect of acute and sustained cyclosporine and tacrolimus on muscle sympathetic nerve activity (MSNA) in groups of healthy male volunteers. METHODS AND RESULTS: Acute cyclosporine in normal dose (2.5 mg/kg) increased MSNA from 11 +/- 6 to 19 +/- 8 bursts/min (P < 0.05). Acute cyclosporine in high dose (10 mg/kg) increased MSNA from 13 +/- 6 to 25 +/- 4 bursts/min (P < 0.05) and increased heart rate and mean arterial pressure (heart rate from 64 +/- 8 to 74 +/- 6 b.p.m., MAP from 92 +/- 10 to 105 +/- 8 mmHg; both P < 0.05). Sustained cyclosporine (2.5 mg/kg b.i.d. for 2 weeks) suppressed MSNA from 14 +/- 6 to 8 +/- 7 bursts/min (P < 0.05). Blood pressure increased from 89 +/- 6 to 98 +/- 6 mmHg (P < 0.05). Body weight increased and plasma renin activity was suppressed. Acute tacrolimus in regular dose (0.05 mg/kg) and high dose (0.20 mg/kg) had no effect on MSNA and blood pressure. Sustained tacrolimus (0.05 mg/kg b.i.d. for 2 weeks) had no effect on blood pressure, body weight and plasma renin activity, but decreased MSNA from 14 +/- 6 to 8 +/- 5 bursts/min (P < 0.05). CONCLUSION: Sympathetic overactivity plays a role in the acute hypertensive action of cyclosporine. Cyclosporine given during 2 weeks increases blood pressure and suppresses MSNA, possibly by volume retention. Tacrolimus, in the presently applied dosages, does not cause hypertension or sympathetic overactivity. However, sustained tacrolimus also suppresses sympathetic activity, the reason of which is unclear.


Subject(s)
Calcineurin Inhibitors , Cyclosporine/administration & dosage , Cyclosporine/adverse effects , Hypertension/chemically induced , Hypertension/physiopathology , Immunosuppressive Agents/adverse effects , Sympathetic Nervous System/drug effects , Sympathetic Nervous System/physiopathology , Tacrolimus/adverse effects , Blood Pressure/drug effects , Body Weight/drug effects , Dose-Response Relationship, Drug , Heart Rate/drug effects , Humans , Immunosuppressive Agents/administration & dosage , Male , Renin/blood , Tacrolimus/administration & dosage
16.
Transplantation ; 73(5): 732-6, 2002 Mar 15.
Article in English | MEDLINE | ID: mdl-11907418

ABSTRACT

BACKGROUND: The side effects of cyclosporine, nephrotoxicity and hypertension, contribute to long-term renal graft failure and cardiovascular morbidity in graft recipients. It is not clear whether tacrolimus is as nephrotoxic and hypertensive as cyclosporine. Data on this subject are not consistent because of differences in dosage and duration of treatment and the presence of comorbidity in the studied patients. A comparison of both drugs with respect to renal hemodynamics and blood pressure has not been performed yet in healthy subjects. METHODS: We studied blood pressure, glomerular filtration rate, and effective renal plasma flow in eight healthy subjects at baseline and after 2 weeks administration of cyclosporine and tacrolimus, in randomized order. Trough levels of either drug were within the currently recommended therapeutical range of 100-200 ng/ml for cyclosporine and 5-15 ng/ml for tacrolimus. RESULTS: Tacrolimus did not influence renal hemodynamic parameters, in contrast to cyclosporine. During cyclosporine, glomerular filtration rate decreased from 98+/-9 ml/min/1.732 to 85+/-10 ml/min/1.732 (P<0.05), and ERPF decreased from 597+/-108 ml/min/1.732 to 438+/-84 ml/min/1.732 (P<0.01). Mean arterial blood pressure increased from 93+/-8 mmHg to 108+/-10 mmHg (P<0.05) during cyclosporine and remained unchanged during tacrolimus. CONCLUSIONS: We conclude that tacrolimus given during 2 weeks in the currently advised dosage has no unfavorable effects on renal hemodynamics and blood pressure in healthy individuals. The use of tacrolimus in organ transplant recipients may in the long-term lead to better renal function and less cardiovascular morbidity than the use of cyclosporine.


Subject(s)
Blood Pressure/drug effects , Cyclosporine/adverse effects , Immunosuppressive Agents/adverse effects , Kidney/drug effects , Tacrolimus/adverse effects , Adult , Glomerular Filtration Rate/drug effects , Hemodynamics/drug effects , Humans , Kidney/physiology , Male , Renal Plasma Flow/drug effects
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