Unpredictable mealtimes rather than social jetlag affects acquisition and retention of hippocampal dependent memory.

Some degree of circadian rhythm disruption is hard to avoid in today's society. Along, with many other deleterious effects, circadian rhythm disruption impairs memory. One way to study this is to expose rats to daylengths that are outside the range of entrainment. As a result, circadian processes and behaviors occur during phases of the light dark cycle in which they typically would not. Even brief exposures to these day lengths can impair hippocampal dependent memory. In a recent report, we created an unentrainable light dark cycle that was intended to resemble aspects of social jetlag. As predictable mealtime impacts circadian entrainment, in that report, we also created an unpredictable meal schedule with the idea that failure to entrain to a meal might afford a disadvantage in some instances. Both of these manipulations impaired retention in a spatial water plus-maze task. Using the same manipulations, the present study investigated their effects on acquisition in distributed and massed spatial water plus-maze paradigms. As in other reports with unentrainable daylengths, acquisition was not affected by our lighting manipulation. Conversely, in accordance with our past report, unpredictable mealtimes had a harmful effect on hippocampal dependent memory. Notably, impaired acquisition in the distributed version, and impaired retention in the massed version. In tandem, these data suggest that failure to consolidate or retrieve the information is the likely culprit. The unpredictable mealtime manipulation offers a unique opportunity to study the effects of circadian entrainment on memory.

Binding of simian virus 40 large T antigen from virus-infected monkey cells to wild-type and mutant viral replication origins.

The binding of purified simian virus 40 (SV40) large T antigen (T) from monkey cells infected with wild-type SV40 virus to viral replication origin-containing DNA fragments was studied by DNase footprinting and restriction endonuclease protection methods. A strong affinity binding site (site 1) of 30 base-pairs and a second, adjacent 40 base-pair lower affinity binding site (site 2), which includes the origin of replication, were detected in these assays. These sites appear identical to those previously noted in similar assays performed with the Ad2 + D2 (D2) T protein. Heating T prior to incubation with DNA significantly increased the binding to these two sites, and the order of binding did not change. Moreover, protection of sequences was observed on both strands in these two sites suggesting that both strands can participate in binding of T to these two sites. Studies with DNAs from two internal site 2 deletion mutants as well as with a DNA fragment lacking the distal 13 base-pairs of site 2 revealed that sequences in the "early" portion of site 2 are sufficient for T binding to the intact site. Furthermore, use of a new assay that measures protection of DNA sequences from specific restriction enzyme cleavage revealed that site 2 can be subdivided into two subsites, 2A and 2B, where 2A corresponds to the above-noted early segment of this locus. In titration experiments, the affinity of 2A for T was greater than that of 2B. Hence, binding to a major portion of the replication initiation sequence (i.e. site 2) is the product of at least two interactions. Finally, analyses performed with DNA from a site 1 deletion mutant, cs1085, revealed that prior binding of T to this locus did not facilitate its binding to site 2. The opposite effect was observed when D2T was employed in these assays. Thus, although similar in many respects, these proteins display a detectable difference in their DNA binding mechanisms.

Radiation dose reduction in the neonatal intensive care unit. Comparison of three gadolinium oxysulfide screen-film combinations.

Infant radiation exposure in the neonatal intensive care unit was quantitated by thermoluminescent dosimetry in 513 mobile unit roentgen examinations of the chest and abdomen. Three combinations of gadolinium oxysulfide intensifying screens and radiographic films were compared. The skin entrance dose in millirads at the mid-chest, mid-abdomen and symphysis pubis levels was measured. Radiation dose reductions of 52% and 68% were achieved using the intermediate and fast combinations relative to the near par speed standard combination. Comparison of the relative line pair resolution of the three combinations under clinical conditions was done and subjective comparison of image detail and image mottle was made by two radiologists. The standard and intermediate speed combinations were considered very acceptable for general neonatal diagnostic interpretation but the fastest combination was not considered acceptable for general purposes. Because of the decreased radiation dose, the intermediate speed combination is now used for all routine neonatal radiography at our institution. The near par speed combination is now used only occasionally for "high-detail" examinations. The fastest combination has a limited role for frequently repeated, less critical studies, such as tube or catheter placement or routine follow-up examinations.

Techniques for evaluating selected reproductive disorders of stallions.

Numerous techniques may be used for evaluation of the different reproductive disorders of the stallion. Approaches may vary from real-time ultrasonography and biopsy for evaluating testicular tumors to use of special assays for evaluating sperm or plasma for presence of antisperm antibodies. This communication addresses techniques used to evaluate five relatively uncommon, but perplexing, disorders of breeding stallions: (1) seminal vesiculitis, (2) hemospermia associated with idiopathic urethral defects, (3) acrosomal dysfunction, (4) abnormal spermatozoal chromatin, and (5) azoospermia.

Estrous cycle characteristics and response to estrus synchronization in mammoth asses (Equus asinus americanus).

Breeding records from a herd of mammoth asses (Equus asinus americanus) maintained on pasture in southeast Texas from 1990 to 1998 were reviewed. Jennies were pasture or hand mated, and estrus was either observed while the jennies were on pasture or when exposed to a jack after being penned. Eighty-one estrus periods and 43 diestrus intervals were recorded in 33 jennies over 4 seasons of the year (January-March, April-June, July-September, and October-December). Estrous cycle length and the duration of estrus were similar among seasons. Over all seasons, estrous cycle length was 23.3 +/- 2.6 d, duration of estrus was 5.9 +/- 2.1 d, and diestrus length was 17.4 +/- 2.6 d (mean +/- SD). During these same 9 yr, 58 injections of PGF2 alpha (5 mg, i.m.) were administered to 38 jennies without regard to stage of estrous cycle. Seventy-six percent (44/58) of the jennies showed signs of estrus after PGF2 alpha treatment, with an interval to estrus of 4.4 +/- 1.6 d and a duration of estrus of 5.6 +/- 1.7 d. Two estrus synchronization schemes were also assessed. Trial 1 was performed in October to November 1996, and Trial 2 was performed in February to March 1998. In Trial 1 (Group PE + PGF, n = 10), each jenny was injected intramuscularly once daily for 10 d with 150 mg progesterone and 10 mg estradiol-17 beta in sesame oil, and PGF2 alpha (10 mg) was injected intramuscularly on the last day of treatment. In Trial 2 (Group PGF-2X, n = 11), each jenny was injected intramuscularly twice, 16 d apart, with 10 mg PGF2 alpha. All Group PE + PGF jennies responded to treatment. One jenny in Group PGF-2X did not respond to either injection of PGF2 alpha, while 2 jennies responded to the first but not the second PGF2 alpha injection (8 of 11 jennies returned to estrus and ovulated after the second PGF2 alpha injection). Duration of estrus was 6.8 +/- 1.9 d for Group PE + PGF and 7.1 +/- 1.8 d for Group PGF-2X jennies. Interval to estrus and interval to ovulation following the last treatment were 9.0 +/- 0.9 d and 14.5 +/- 1.7 d, respectively, in Group PE + PGF jennies, and 4.5 +/- 0.9 d and 10.4 +/- 1.8 d, respectively, for Group PGF-2X jennies. In summary, estrous cycle characteristics of mammoth asses are similar to those reported for standard jennies, and estrus synchronization schemes used in horses are effective in mammoth asses.

Rectal tears in the horse: an analysis of 35 cases.

The records of 35 horses with Grade 3 or 4 rectal tears, presented to the Veterinary Medical Center at Texas A & M University over a five year period, were reviewed. Grade 3 tears were sub-classified according to whether the remaining tissue was serosa (Grade 3a) or mesorectum (Grade 3b). Five horses were destroyed on presentation and 30 were treated by primary suture closure (8 horses), faecal diversion alone (9 horses) or in combination with suture closure (11 horses) and packing of the tear with medicated gauze sponges (two horses). Faecal diversion was achieved with a temporary indwelling rectal liner (TIRL) in 19 horses and colostomy in one. Survival was related to classification of the tear, efficacy of first aid measures administered at time of injury and method of treatment. Seventy-four per cent of horses with Grade 3a tears and 44 per cent of those with Grade 3b tears survived. Grade 4 tears had a grave prognosis. Horses given adequate first aid before admission had a better survival rate. With proper patient selection, primary closure of the tear with sutures yielded excellent results. In horses which were not candidates for suture closure alone, a combination of faecal diversion and suturing gave better results than faecal diversion only. In addition, selected horses were treated successfully by packing the rectal tear with gauze sponges. The results demonstrate the value of a TIRL to divert faeces and appropriate first aid measures in treating rectal tears.

Disseminated intravascular coagulation associated with colic in 23 horses (1984-1989).

Disseminated intravascular coagulation (DIC) secondary to colic was diagnosed in 23 horses. Each horse was categorized retrospectively as to the cause of the colic based on surgical and/or necropsy findings: group 1 consisted of 14 horses with compromised intestine that required resection and anastomosis; group 2 consisted of 3 horses with nonstrangulating intestinal displacement and/or impactions; and group 3 consisted of 6 horses with colic associated with enteritis and/or colitis. Horses were considered to be affected with DIC if at least three of five hemostatic parameters were significantly abnormal: decreased antithrombin III (AT III) values, increased level of fibrin degradation products (FDP), thrombocytopenia, prolonged activated partial thromboplastin time, and prolonged prothrombin time. The most consistent hemostatic abnormalities were decreased AT III activity, increased FDP titers, and thrombocytopenia. Clotting times were more variable and did not always correlate with the presence of excessive hemorrhage. Excessive hemorrhage was present during surgery in seven horses and occurred within 1 to 12 hours after surgery in nine other horses. In addition to treatment of the primary disease, 19 horses received treatment for DIC consisting of heparin and/or plasma or fresh whole blood transfusions. Heparin alone was used in 12 horses. Heparin, in addition to fresh whole blood transfusions or fresh plasma, was administered to four horses. Three horses were treated with plasma alone. Four other horses were not treated specifically for the DIC. Eight horses (34%) survived the acute coagulopathy. Although a greater proportion of the surviving horses received heparin therapy (87.5%; 7/8) than did those that died (60%; 9/15), the difference was not statistically significant (P = 0.345).(ABSTRACT TRUNCATED AT 250 WORDS)

Medical management of right dorsal colitis in 5 horses: a retrospective study (1987-1993).

Right dorsal colitis in horses has been associated with administration of phenylbutazone. Although reports of right dorsal colitis in this species have described surgical treatment associated with a poor prognosis, we have had success treating this condition medically. This report describes 5 horses with right dorsal colitis confirmed during celiotomy that were initially managed medically. All horses had a history of intermittent abdominal pain; weight loss was noted in only 1 horse. The doses (2.0 to 4.6 mg/kg PO bid) and duration (5 to 30 days) of administration of phenylbutazone were not unusually high relative to those recommended (4.4 mg/kg PO bid). Hypoproteinemia and hypoalbuminemia were observed in all horses at the time of admission; packed cell volume was low in 4 horses, and hypocalcemia was also observed in 4 horses. Three of 5 horses (60%) appeared to respond to dietary management and discontinuation of administration of nonsteroidal anti-inflammatory drugs. Dietary management consisted of feeding pelleted feed, and restricting or eliminating roughage for a period of at least 3 months. Two horses developed strictures of the right dorsal colon. One horse that developed a colonic stricture, possibly because its owners did not comply with recommendations for management, was subsequently treated surgically. The remaining horse that developed a stricture of the right dorsal colon was euthanized. These data indicate that some horses with right dorsal colitis can be successfully managed with medical treatment.

Myoelectric activity of the cecum and proximal loop of the ascending colon in cows.

Six Jersey cows were implanted with 8 pairs of bipolar electrodes: 1 in the jejunum, 1 in the ileum, 3 in the cecum, and 3 in the proximal loop of the ascending colon (PLAC). Myoelectric activity was recorded at 2- to 3-day intervals, 3 times for 8 hours or 4 times for 6 hours, using a computer-based oscillograph and data-acquisition program. Mean (+/- SD) duration of the migrating myoelectric complex (MMC) in the ileum was 84.52 +/- 4.87 minutes. Phases I and II of the MMC lasted significantly (P < 0.05) longer than phase III. Two types (A and B) of cyclic activity were found in the cecum and PLAC. Cyclic activity type A was observed predominantly in the cecum, and type B was observed exclusively in the PLAC. Phase III of the MMC in the ileum was accompanied by hyperactivity type A at the level of the ileocecocolic junction in 60.90 +/- 12.65% of the MMC. Twenty-seven types of orally and aborally propagated spike sequences, involving the cecum and PLAC, were found. They were most frequent when an MMC phase III was observed in the ileum, and least frequent when an MMC phase I was observed in the ileum (P < 0.05). All electrode sites of the cecum and PLAC served as pacemaker areas. Propagated and nonpropagated spikes were found at all electrode sites of the cecum and PLAC. Although propagated spikes lasted significantly (P < 0.05) longer than nonpropagated spikes, a clear distinction on the basis of duration could not be defined between the 2 spike types because broad overlapping of duration existed.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary effects of butorphanol tartrate intravenously administered for placement of duodenal cannulae in isoflurane-anesthetized yearling steers.

Cardiopulmonary effects of IV administered butorphanol tartrate (BUT) were assessed in 7 yearling steers medicated with atropine and anesthetized with guaifenesin, thiamylal sodium, and isoflurane in O2 for surgical placement of duodenal cannulae. Heart rate, respiratory rate, arterial blood pressures, pHa, PaCO2, PaO2, arterial [HCO3-], esophageal temperature, and end-tidal isoflurane concentrations were measured before and after IV administration of BUT (10 mg). Mean respiratory rate increased significantly (P less than 0.05) only at 45 and 60 minutes after BUT administration. Mean respiratory rate was 26 +/- 6.3 breaths/min before BUT administration and 46 +/- 12.1 breaths/min 60 minutes after BUT administration. Arterial blood pressures were increased significantly (P less than 0.05) at all times, except 5 minutes after BUT administration. The mean value for mean arterial pressure was 76 +/- 9.6 mm of Hg before BUT injection and 117 +/- 12.6 mm of Hg 60 minutes after BUT injection. Mean values for pHa and arterial [HCO3-] were significantly (P less than 0.05) higher at 60 minutes after BUT administration (baseline, pH = 7.25 +/- 0.04 and [HCO3-] = 29.9 +/- 3.5 mEq/L; 60 minutes after BUT, pH = 7.28 +/- 0.03 and [HCO3-] = 33.0 +/- 1.8 mEq/L). Although some statistically significant changes were recorded, IV administration of BUT to these steers did not have a marked effect on the cardiopulmonary variables measured.

Comparative pharmacokinetics of caffeine and three metabolites in clinically normal horses and donkeys.

OBJECTIVE: To determine whether clearance of capacity-limited drugs in horses differs from that in donkeys by comparing the serum disposition of caffeine and its metabolites, theophylline, theobromine, and paraxanthine after i.v. administration of caffeine to horses and donkeys. ANIMALS: 4 healthy horses and 5 healthy donkeys. PROCEDURE: Blood samples were collected from each animal at time 0 (before) and 5, 10, 15, 20, 30, and 45 minutes, and 1, 2, 3, 4, 6, 8, 12, 24, 30, 36, 48, 54, 60, 72, and 96 hours after IV administration of a bolus of caffeine. Serum was analyzed in triplicate by high-performance liquid chromatography to determine caffeine, theophylline, theobromine, and paraxanthine concentrations. The serum concentration-time curves for each animal were analyzed separately to estimate model-independent pharmacokinetic variables. RESULTS: Mean pharmacokinetic values for caffeine, theophylline, and paraxanthine did not differ significantly in horses, compared with donkeys. Mean peak serum concentration of theobromine was significantly higher in donkeys, compared with horses. CONCLUSION: Clearance of the capacity-limited drug caffeine does not appear to differ in horses, compared with donkeys. CLINICAL RELEVANCE: For some drugs that undergo hepatic metabolism, the dose and dose interval used for horses may be appropriate for use in donkeys.

Use of orthopedic markers for quantitative determination of proximal radial and ulnar growth in foals.

Cortical bone screws were implanted into the proximal portion of the right and left radius and ulna of 6 newborn Quarter Horse foals as radiographic markers for measurement of growth. Distance between markers on a lateral radiographic view was measured. Radiographs were taken at 2-week intervals until the horses were 8 weeks old, at 4-week intervals until they were 48 weeks old, and at 12-week intervals until they were 72 weeks old. The proximal radius and ulna grew at similar rates during the 72-week period of evaluation, and growth continued throughout 72 weeks. The proximal radius grew 3.5 cm, and the ulna grew 3.4 cm. Although the rates of growth were similar, growth from the ulnar physis contributed only to the length of the olecranon; growth was not transmitted to the ulnar diaphysis distal to the cubital joint. The proximal radius slid distally in relation to the ulna as growth occurred at the proximal radial physis. These findings suggest that transfixing the ulna to the radius while growth is occurring at the proximal radial physis impedes the natural shifting process, and subluxation of the elbow can result. Severity of subluxation would be inversely related to the age of the horse at the time of transfixation.

Pharmacokinetics of flunixin meglumine in donkeys, mules, and horses.

OBJECTIVE: To compare serum disposition of flunixin meglumine after i.v. administration of a bolus to horses, donkeys, and mules. ANIMALS: 3 clinically normal horses, 5 clinically normal donkeys, and 5 clinically normal mules. PROCEDURE: Blood samples were collected at time zero (before) and 5, 10, 15, 30, and 45 minutes, and at 1, 1.25, 1.5, 1.75, 2, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, and 8 hours after i.v. administration of a bolus of flunixin meglumine (1.1 mg/kg of body weight). Serum was analyzed in duplicate by the use of high-performance liquid chromatography for determination of flunixin meglumine concentrations. The serum concentration-time curve for each horse, donkey, and mule were analyzed separately to estimate noncompartmental pharmacokinetic variables RESULTS: Mean (+/-SD) area under the curve for donkeys (646 +/- 148 minute x microg/ml) was significantly less than for horses (976 +/- 168 minute x microg/ml) or for mules (860 +/- 343 minute x microg/ml). Mean residence time for donkeys (54.6 +/- 7 minutes) was significantly less than for horses (110 +/- 24 minutes) or for mules (93 +/- 30 minutes). Mean total body clearance for donkeys (1.78 +/- 0.5 ml/kg/h) was significantly different from that for horses (1.14 +/- 0.18 ml/kg/h) but not from that for mules (1.4 +/- 0.5 ml/kg/h). Significant differences were not found between horses and mules for any pharmacokinetic variable. CONCLUSION AND CLINICAL RELEVANCE: Significant differences exist with regard to serum disposition of flunixin meglumine in donkeys, compared with that for horses and mules. Consequently, flunixin meglumine dosing regimens used in horses may be inappropriate for use in donkeys.

Comparative pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone in clinically normal horses and donkeys.

OBJECTIVE: To compare plasma disposition of phenylbutazone and its metabolite oxyphenbutazone after i.v. administration of phenylbutazone in horses and donkeys. ANIMALS: 4 clinically normal horses and 6 clinically normal donkeys. PROCEDURE: Blood samples were collected from each animal at time 0 (before) and 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, 360, and 480 minutes after i.v. administration of a bolus dose of phenylbutazone. Serum was analyzed in triplicate by use of high-performance liquid chromatography for determination of phenylbutazone and oxyphenbutazone concentrations. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate model-independent pharmacokinetic variables. RESULTS: Significant differences were found in several pharmacokinetic variables of phenylbutazone and oxyphenbutazone in horses, compared with donkeys. Mean total body clearance of phenylbutazone in horses was fivefold less than that in donkeys (29.3 and 170.3 ml/kg/h, respectively). Mean values for area under the curve and mean residence time in horses (118.3 micrograms/h/ml and 3.6 hours, respectively) were significantly greater than values in donkeys (28.3 micrograms/h/ml and 1.7 hours, respectively). Mean values for apparent volume of distribution at steady state were not significantly different between horses and donkeys. For oxyphenbutazone, mean time to peak concentration in donkeys was significantly less than that in horses (1.6 and 6.4 hours, respectively). CONCLUSION: Phenylbutazone clearance in donkeys was higher than that in horses, and appearance of the metabolite oxyphenbutazone in serum was more rapid in donkeys than in horses, indicating that hepatic metabolism of phenylbutazone is more rapid in donkeys than in horses. CLINICAL RELEVANCE: Because serum concentration of phenylbutazone after single i.v. bolus administration (4.4 mg/kg of body weight) decreases more rapidly in donkeys, compared with horses, phenylbutazone may require more frequent administration in donkeys to achieve therapeutic efficacy.

Effect of antimicrobial solution lavage on the palmar digital tendon sheath in horses.

Sixteen horses were allotted to 4 groups of 4 horses each to evaluate the effect of tendon sheath lavage with 4 solutions (balanced electrolyte solution, 0.1% povidone-iodine, 0.5% povidone-iodine, and 0.5% chlorhexidine). The synovitis caused by 0.1% povidone-iodine lavage was not appreciably worse than that caused by balanced electrolyte solution lavage, but the 0.5% povidone-iodine and chlorhexidine lavages caused severe synovitis, and, therefore, should not be used for tendon sheath lavage.

Pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone in miniature donkeys.

OBJECTIVE: To describe the pharmacokinetics of phenylbutazone and oxyphenbutazone after IV administration in miniature donkeys. ANIMALS: 6 clinically normal miniature donkeys. PROCEDURE: Blood samples were collected before and 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, 360, and 480 minutes after IV administration of phenylbutazone (4.4 mg/kg of body weight). Serum was analyzed in triplicate by use of high-performance liquid chromatography for determination of phenylbutazone and oxyphenbutazone concentrations. The serum concentration-time curve for each donkey was analyzed separately to estimate model-independent pharmacokinetic variables. RESULTS: Serum concentrations decreased rapidly after IV administration of phenylbutazone, and they reached undetectable concentrations within 4 hours. Values for mean residence time ranged from 0.5 to 3.0 hours (median, 1.1 hour), whereas total body clearance ranged from 4.2 to 7.5 ml/kg/min (mean, 5.8 ml/kg/min). Oxyphenbutazone appeared rapidly in the serum; time to peak concentration ranged from 13 to 41 minutes (mean, 26.4 minutes), and peak concentration in serum ranged from 2.8 to 4.0 mg/ml (mean, 3.5 microg/ml). CONCLUSION AND CLINICAL RELEVANCE: Clearance of phenylbutazone in miniature donkeys after injection of a single dose (4.4 mg/kg, IV) is rapid. Compared with horses, miniature donkeys may require more frequent administration of phenylbutazone to achieve therapeutic efficacy.

Radiolucencies with distinct borders.

The differential diagnosis of circumscribed radiolucencies or those with distinct borders requires careful evaluation of lesion-specific characteristics. This evaluation is necessary because of the variable prognosis and possible aggressiveness of lesions that may fall into this category, which also contains many benign conditions. This section reviews the clinical features, radiographic appearance, histopathologic findings, and treatment recommendations for a selected group of lesions.

Effects of denervation of the digit of the horse.

A study was conducted in an effort to explain why digital necrosis sometimes follows neurectomy in the horse. Six horses were subjected to unilateral section of the medial and lateral palmar nerves. Arteriography was done on each digit prior to surgery. Terminally, arteriography was repeated. Sections of bone, nerve, artery, skin, coronary band, and deep flexor tendon were examined histologically. Changes in arterial pattern and bone quality were noted. During the study, 2 of the horses had clinical signs of digital necrosis. The composite findings suggested trauma or infection, or both, of the denervated digit as the main cause(s) of the digital necrosis. Osteolysis was believed to be the primary contributing factor in disruption and collapse of the supporting structures of the foot.

Temporary indwelling rectal liner for use in horses with rectal tears.

A temporary indwelling liner was surgically installed in 17 horses with grade III or grade IV rectal tears. The rectal tears of 9 of the horses healed. The remaining 8 horses developed peritonitis as a result of peritoneal contamination before surgery, a change in grade of the tear, or material failure.

Peritoneal lavage in the horse.

Eight horses ranging in age from 4 days to 9 years were treated for peritonitis. Escherichia coli was isolated in four cases and Nocardia sp in one case. In each case, a catheter placed in the peritoneal cavity allowed drainage of a large amount of purulent fluid. Retrograde peritoneal lavage was performed through a Foley catheter or medical tubing, using Ringer's lactate solution containing kanamycin, povidone iodine, or nitrofurazone. All except two horses responded well to repeated lavage.