Effects of hindgut acidosis on metabolism, inflammation, and production in dairy cows consuming a standard lactation diet.

Postruminal intestinal barrier dysfunction caused by excessive hindgut fermentation may be a source of peripheral inflammation in dairy cattle. Therefore, the study objectives were to evaluate the effects of isolated hindgut acidosis on metabolism, inflammation, and production in lactating dairy cows. Five rumen-cannulated lactating Holstein cows (32.6 ± 7.2 kg/d of milk yield, 242 ± 108 d in milk; 642 ± 99 kg of body weight; 1.8 ± 1.0 parity) were enrolled in a study with 2 experimental periods (P). During P1 (4 d), cows were fed ad libitum a standard lactating cow diet (26% starch dry matter) and baseline data were collected. During P2 (7 d), all cows were fed the same diet ad libitum and abomasally infused with 4 kg/d of pure corn starch (1 kg of corn starch + 1.25 L of H2O/infusion at 0600, 1200, 1800, and 0000 h). Effects of time (hour relative to the first infusion or day) relative to P1 were evaluated using PROC MIXED in SAS (version 9.4; SAS Institute Inc.). Infusing starch markedly reduced fecal pH (5.84 vs. 6.76) and increased fecal starch (2.2 to 9.6% of dry matter) relative to baseline. During P2, milk yield, milk components, energy-corrected milk yield, and voluntary dry matter intake remained unchanged. At 14 h, plasma insulin and ß-hydroxybutyrate increased (2.4-fold and 53%, respectively), whereas circulating glucose concentrations remained unaltered. Furthermore, blood urea nitrogen increased at 2 h (23%) before promptly decreasing below baseline at 14 h (13%). Nonesterified fatty acids tended to decrease from 2 to 26 h (40%). Circulating white blood cells and neutrophils increased on d 4 (36 and 73%, respectively) and somatic cell count increased on d 5 (4.8-fold). However, circulating serum amyloid A and lipopolysaccharide-binding protein concentrations were unaffected by starch infusions. Despite minor changes in postabsorptive energetics and leukocyte dynamics, abomasal starch infusions and the subsequent hindgut acidosis had little or no meaningful effects on biomarkers of immune activation or production variables.

Effects of maintaining eucalcemia following immunoactivation in lactating Holstein dairy cows.

Periparturient hypocalcemia is a common metabolic disorder and it is ostensibly associated with negative health and production outcomes. Acute infection also markedly decreases circulating Ca, but the reasons for and consequences of it on physiological and immunological parameters are unknown. Objectives were to evaluate the effects of maintaining eucalcemia on production, metabolic, and immune variables following an intravenous lipopolysaccharide (LPS) challenge. Twelve multiparous lactating Holstein cows (717 ± 20 kg of body weight; 176 ± 34 d in milk; parity 3 ± 0.2) were enrolled in a study containing 2 experimental periods (P); during P1 (3 d), cows consumed feed ad libitum and baseline values were obtained. At the initiation of P2 (4 d), cows were randomly assigned to 1 of 2 treatments: (1) LPS administered (LPS-Con; 0.5 µg/kg of body weight LPS; n = 6) or (2) LPS administered + eucalcemic clamp (LPS-Ca; 0.5 µg/kg of body weight LPS; Ca infusion; n = 6). Cows were fasted for the first 12 h during P2. After LPS administration, ionized Ca was determined every 15 min for 6 h and every 30 min for an additional 6 h and intravenous Ca infusion was adjusted in LPS-Ca cows to maintain eucalcemia. Blood ionized Ca was decreased 23% for the first 12 h postbolus in LPS-Con cows, and by design, Ca infusion prevented hypocalcemia. To maintain eucalcemia for the 12 h, 13.7 g of Ca was infused. The total Ca deficit (including Ca not secreted into milk) accumulated over the 12 h was 10.4 and 20.2 g for the LPS-Con and LPS-Ca treatments, respectively. Mild hyperthermia (0.8°C) occurred for ∼6 h post-LPS administration relative to P1. From 6 to 7 h postbolus rectal temperature from LPS-Ca cows was increased (0.6°C) relative to LPS-Con cows. On d 1 of P2, milk yield decreased (61%) in both treatments relative to P1. Relative to LPS-Con cows, milk yield decreased (15%) in LPS-Ca cows during P2. Overall, circulating LPS-binding protein continuously increased postbolus, and at 24 h LPS-binding protein levels in LPS-Ca cows were increased (80%) relative to LPS-Con cows. During P2, serum amyloid A increased (4-fold) in both treatments relative to P1. Administering LPS initially decreased circulating neutrophils, then cell counts progressively increased with time. Calcium infusion decreased neutrophil counts (40%) from 9 to 12 h postbolus relative to LPS-Con cows. Neutrophil function, as assessed by oxidative burst and myeloperoxidase production, did not differ due to treatment. In summary, maintaining eucalcemia (via intravenous Ca infusion) during an immune challenge appeared to intensify inflammation and adversely affect lactation performance.

Energetic metabolism, milk production, and inflammatory response of transition dairy cows fed rumen-protected glucose.

Objectives were to evaluate the effects of rumen-protected glucose (RPG) supplementation on milk production, post-absorptive metabolism, and inflammatory biomarkers in transition dairy cows. Fifty-two multiparous cows were blocked by previous 305-d mature-equivalent milk (305ME) yield and randomly assigned to 1 of 2 iso-energetic and iso-nitrogenous treatments: (1) control diet (CON; n = 26) or (2) a diet containing RPG (pre-fresh 5.3% of dry matter and 6.0% of dry matter postpartum; n = 26). Cows received their respective dietary treatments from d -21 to 28 relative to calving, and dry matter intake was calculated daily during the same period. Weekly body weight, milk composition, and fecal pH were recorded until 28 d in milk (DIM), and milk yield was recorded through 105 DIM. Blood samples were collected on d -7, 3, 7, 14, and 28 relative to calving. Data were analyzed using repeated measures in the MIXED procedure (SAS Institute Inc., Cary, NC) with previous 305ME as a covariate. Fecal pH was similar between treatments and decreased (0.6 units) postpartum. Dry matter intake pre- and postpartum were unaffected by treatment, as was milk yield during the first 28 or 105 DIM. Milk fat, protein, and lactose concentration were similar for both treatments. Blood urea nitrogen and plasma glucose concentrations were unaffected by treatment; however, results showed increased concentration of circulating insulin (27%), lower nonesterified fatty acids (28%), and lower postpartum ß-hydroxybutyrate (24%) in RPG-fed cows. Overall, circulating lipopolysaccharide-binding protein and haptoglobin did not differ by treatment, but at 7 DIM, RPG-fed cows had decreased lipopolysaccharide-binding protein and haptoglobin concentrations (31 and 27%, respectively) compared with controls. Supplemental RPG improved some biomarkers of post-absorptive energetics and inflammation during the periparturient period, changes primarily characterized by increased insulin and decreased nonesterified fatty acids concentrations, with a concomitant reduction in acute phase proteins without changing milk production and composition.

Validating a heat stress model: The effects of an electric heat blanket and nutritional plane on lactating dairy cows.

The efficacy of an electric heat blanket (EHB) has previously been confirmed as an alternative method to evaluate heat stress (HS). However, a pair-feeding design has not been used with the EHB model. Therefore, study objectives were to determine the contribution of the nutritional plane to altered metabolism and productivity during EHB-induced HS. Multiparous Holstein cows (n = 18; 140 ± 10 d in milk) were subjected to 2 experimental periods (P); during P1 (4 d), cows were in thermoneutral conditions with ad libitum feed intake. During P2 (4 d), cows were assigned to 1 of 2 treatments: (1) thermoneutral conditions and pair-fed (PF; n = 8) or (2) EHB-induced HS with ad libitum feed intake (n = 10). Overall, the EHB increased rectal temperature, vaginal temperature, skin temperature, and respiration rate (1.4°C, 1.3°C, 0.8°C, and 42 breaths/min, respectively) relative to PF cows. The EHB reduced dry matter intake (DMI; 47%) and, by design, PF cows had a similar pattern and extent of decreased DMI. Milk yield decreased in EHB and PF cows by 27.3% (12.1 kg) and 13.4% (5.4 kg), respectively, indicating that reduced DMI accounted for only ∼50% of decreased milk synthesis. Milk fat content tended to increase (19%) in the EHB group, whereas in the PF cows it remained similar relative to P1. During P2, milk protein and lactose contents tended to decrease or decreased (1.3 and 2.2%, respectively) in both EHB and PF groups. Milk urea nitrogen remained unchanged in PF controls but increased (34.2%) in EHB cows relative to P1. The EHB decreased blood partial pressure of CO2, total CO2, HCO3, and base excess levels (17, 16, 17, and 81%, respectively) compared with those in PF cows. During P2, the EHB and PF cows had similar decreases (4%) in plasma glucose content, but no differences in circulating insulin were detected. However, a group by day interaction was detected for plasma nonesterified fatty acids; levels progressively increased in PF controls but remained unaltered in the EHB cows. Blood urea nitrogen increased in the EHB cows (61%) compared with the PF controls. In summary, utilizing the EHB model indicated that reduced nutrient intake explains only about 50% of the decrease in milk yield during HS, and the postabsorptive changes in nutrient partitioning are similar to those obtained in climate-controlled chamber studies. Consequently, the EHB is a reasonable and economically feasible model to study environmental physiology of dairy cows.

Effects of continuous and increasing lipopolysaccharide infusion on basal and stimulated metabolism in lactating Holstein cows.

Experimental objectives of this study were to characterize the systemic and intracellular metabolic response to continuous lipopolysaccharide (LPS) infusion in mid-lactation Holstein cows (169 ± 20 d in milk; 681 ± 16 kg of body weight). Following 3 d of acclimation, cows were enrolled in 2 experimental periods (P). During P1 (3 d), cows were fed ad libitum and baseline data were collected. In P2 (8 d), cows were assigned to 1 of 2 treatments: (1) saline-infused and pair-fed (CON-PF; i.v. sterile saline at 40 mL/h; n = 5) or (2) LPS-infused and fed ad libitum (LPS-AL; Escherichia coli O55:B5 at 0.017, 0.020, 0.026, 0.036, 0.055, 0.088, 0.148, and 0.148 µg/kg of body weight per hour for d 1 through 8, respectively; n = 6). During P2, CON-PF cows were pair-fed to LPS-AL cows to eliminate confounding effects of dissimilar nutrient intake. Blood samples were collected on d 1 and 2 of P1 and d 1, 3, 5, and 7 of P2. Following the P2 d 7 a.m. milking, adipose tissue, skeletal muscle, and liver biopsies were collected for reverse transcription quantitative PCR and Western blot analysis. To assess whole-body nutrient trafficking, an i.v. glucose tolerance test (GTT) was performed following the a.m. milking on P2 d 8; 4 h after the GTT, cows received an epinephrine challenge. During P2, there were no treatment differences in circulating glucose. Relative to P1, CON-PF cows had or tended to have decreased plasma ß-hydroxybutyrate and insulin (29 and 47%, respectively) during P2, whereas neither variable changed in LPS-AL cows, leading to an overall increase in ß-hydroxybutyrate and insulin (41 and 140%, respectively) relative to CON-PF cows. Circulating nonesterified fatty acids were increased from d 1 to 3 and subsequently decreased from d 3 to 7 in cows from both treatments. Blood urea nitrogen gradually decreased in CON-PF cows and increased in LPS-AL cows from d 1 to 5 of P2, resulting in an overall 25% increase in LPS-AL versus CON-PF cows. In response to the GTT, the glucose and insulin area under the curve were increased 33 and 56%, respectively, in LPS-AL compared with CON-PF cows; changes reflective of whole-body insulin resistance. However, protein abundance of insulin signaling markers within muscle, liver, and adipose tissue were similar between treatments. There were no observable treatment differences in the glucose or nonesterified fatty acids response to the epinephrine challenge. No treatment differences were observed in hepatic mRNA abundance of key gluconeogenic or lipid export enzymes. In conclusion, chronic LPS exposure altered multiple parameters of basal and stimulated metabolism, but did not appear to affect the molecular machinery evaluated herein.

Dopaminergic agents affect the ability of brief periods of normal vision to prevent form-deprivation myopia.

Placing a translucent diffuser over the eye of a chick causes the eye to grow excessively, resulting in form-deprivation myopia. For chickens kept on a 12:12 h light/dark cycle, removing the diffuser for 3 h during the light period protects against the excessive growth, but if the bird is kept in the dark for this 3-h period, the protective effect is abolished. Injecting dopamine agonists into the eye during this 3-h dark period restores the protective effect, which can be blocked by dopamine antagonists injected just prior to diffuser removal in the light. These responses are mediated by D2 receptors, suggesting that the protective effect of normal vision against form-deprivation is mediated through the stimulation of dopamine release and activation of D2-dopamine receptors.

A comparison of epidural versus general anesthesia for outpatient endoscopic preperitoneal herniorrhaphy.

OBJECTIVES: To study the efficacy of epidural versus general anesthesia on length of stay, patient recovery and anesthetic-related complications in patients undergoing endoscopic preperitoneal herniorrhaphy. METHODS: One hundred sixty-seven consecutive patients undergoing endoscopic preperitoneal herniorrhaphy from July, 1994, to August, 1995, were retrospectively studied. A total of 243 herniorrhaphies were performed. Four patients required conversion of epidural anesthesia to general anesthesia because of inadequate sensory blockade (67/71; 94% success rate). One-hundred-forty-eight patients were available for review. Sixty-seven patients underwent successful epidural anesthesia during the case, while 81 patients were managed with general anesthesia. RESULTS: Thirty patients (37%) receiving general anesthesia required interventions for nausea compared to only six patients (9.0%) in the epidural anesthesia group (p < 0.001). Thirty patients (37%) in the general anesthesia group required intervention because of complaints of pain, compared to 13 (19.4%) in the epidural group (p < 0.05). There were no differences between the two groups for length of stay in OR, PACU, or total hospital times. CONCLUSIONS: The use of epidural anesthesia during the performance of endoscopic preperitoneal herniorrhaphy was associated with a decrease in the incidence of postoperative pain and nausea. The technique was successful in 94% of the cases in which it was used. Epidural anesthesia is recommended as an effective alternative to general anesthesia for the performance of outpatient endoscopic preperitoneal herniorrhaphy.

Beyond Pittsburgh: protocols for controlled non-heart-beating cadaver organ recovery.

Much of the ethical debate about controlled non-heart-beating cadaver (NHBC) organ recovery has focused on the University of Pittsburgh Medical Center (UPMC) protocol. Some commentators have voiced serious reservations about the ethical acceptability of that protocol; others have argued that the protocol contains sufficiently stringent ethical safeguards to warrant a limited and carefully monitored trial at UPMC. UPMC is not the only organization pursuing controlled NHBC organ procurement, however. The study of organ procurement organizations described in this article suggests that controlled NHBC organ procurement is a practice that, if not yet widespread, is certainly no longer isolated to a few organizations in which it is carefully monitored. Rather, it is being carried out under a variety of circumstances, many of which are less carefully constrained ethically than at the University of Pittsburgh Medical Center. The next stage of the ethical debate should focus on issues that are arising in a variety of settings as the practice spreads.

Pitfalls and limitations of diuretic renography.

We report five pediatric cases that illustrate the methodologic pitfalls and limitations of diuretic renography in suspected ureteropelvic junction obstruction. False-positive studies may be related to such avoidable flaws in methodology as premature diuretic administration, inadequate diuretic dose, and bladder distension, or to recent pyeloplasty. False-negative results may occur despite optimum technique, necessitating a follow-up study for confirmation.

Multiple myeloma and contrast media.

Contrast media administered intravenously are still thought by many to be a major cause of acute renal failure (ARF) in myeloma patients. Recently, several authors found that the predominant risk factors of ARF in myeloma patients are hypercalcemia, dehydration, infection, and Bence Jones proteinuria rather than contrast media. In a review of seven retrospective studies of myeloma patients receiving contrast media, 476 patients were noted to have undergone 568 contrast media studies, with an ARF prevalence of 0.6%-1.25%. One large series showed the incidence of ARF after administration of contrast media to be 0.15% in the general population. Although the administration of contrast media to myeloma patients is not totally risk free, it may be performed if the clinical need arises and the patient is well hydrated.

Localizing and prognostic value of auditory evoked responses in coma after closed head injury.

We studied brainstem auditory evoked responses (BAERs) in 26 comatose patients after head injury, and long-latency auditory evoked responses (AERs) in 24 patients. BAERs-AERs were graded for abnormality to evaluate graded outcome. Only six patients had central BAER abnormalities. AERs were abnormal in 21, and all patients with abnormal BAER had abnormal AER, implying that the major site of injury affected the cerebral hemispheres. BAER was abnormal in only 5 of 12 with decerebration, suggesting that decerebration may occur with diffuse hemispheric injury. BAER (p less than 0.01) and AER (p less than 0.01) strongly correlated with outcome. Preservation of AER and normal BAER indicated good quality of survival; absent AER and normal BAER, survival; and absent AER and abnormal BAER, severe disability or death. BAER-AER predicted outcome as accurately as the detailed neurologic examination and occasionally added predictive power.