Phenibut toxicosis in a dog.

Exercise induced changes in creatine kinase and aspartate aminotransferase activities in the horse: Effects of conditioning, exercise tests and acepromazine

SummaryThis retrospective case series describes clinicopathological data and outcome of hospitalised atypical myopathy (AM) cases in the South‐East of England. The study aimed to describe the frequency of metabolic abnormalities (hyperglycaemia, hyperlactataemia, hypertriglyceridaemia) and outcome in AM cases in the South‐East of England and test the hypothesis that serum creatine kinase (CK) activity and blood glucose, lactate and triglyceride concentrations are associated with outcome. Medical records (2011–2017) from three referral hospitals were reviewed for cases with a clinical diagnosis of AM. A previously described algorithm was applied and cases were included if a diagnosis of AM was considered highly likely. In cases admitted after 2013 known or possible exposure to sycamore trees was also required for inclusion. Sixty‐four animals were included, 44% (28/64) survived. Hyperglycaemia, hyperlactataemia and hypertriglyceridaemia were present in 76%, 89% and 92% of horses on admission, respectively. Survivors had lower blood lactate concentrations (survivors: median 3.5 mmol/L; range 0.5–10.4 mmol/L vs. nonsurvivors: median 7.3 mmol/L; range 2.5–16.5 mmol/L; P = 0.011) and serum CK activities (survivors: median 38,369 U/L; range 7024–570,498 U/L vs. nonsurvivors: median 172,687 U/L; range 2036–570,953 U/L; P = 0.027) on admission when compared to nonsurvivors. Increasing CK activity (P = 0.008) and triglyceride concentrations (P = 0.038) during hospitalisation were associated with nonsurvival. More nonsurvivors required sedation (18/29; 62.1% vs. 4/22; 18.2%; P = 0.002). The prognosis for hospitalised horses with AM is guarded and outcome in this population was associated with admission CK activity and lactate concentrations, and increasing CK activity and triglyceride concentrations and need for sedation during hospitalisation.

We report 2 cases of enormously elevated creatine kinase (CK) activity after training with electromyostimulation (EMS) by 2 young male professional soccer players. In one of them, a single training session with EMS caused exercise-induced rhabdomyolysis with a maximal CK activity of 240 000 U/L. These cases illustrate that unaccustomed EMS exercise may be harmful and can cause rhabdomyolysis even in highly trained athletes and even after 1 single session. Thus, EMS has to be conducted carefully especially by individuals who are known to frequently show notable increases in CK activity even after modest training stimuli. We suggest that EMS should not be applied as sole training stimulus and should not be conducted by strength training beginners. Furthermore, we recommend controlling plasma CK activity and urine color for beginners with EMS when they report strong muscle ache. Athletes with signs of rhabdomyolysis after EMS should be brought to hospital for monitoring of renal function and possible further treatment.

In Memoriam

Therapeutic strategies are needed to treat immune-mediated diseases in dogs. Human intravenous immunoglobulin (hIVIG), approved to treat inflammatory diseases in humans, has been used in dogs with some success in some immune-mediated hematologic and dermatologic disorders. However, cost, supply issues, and safety concerns have limited studies in dogs. Evaluate the feasibility of swine immunoglobulin G (SwIgG) in healthy dogs as a replacement for hIVIG. Three healthy female beagles. Swine IgG purified by column chromatography and injected SC into beagle dogs with or without intradermal injections at predetermined time points. The dogs were observed for up to 3weeks with blood collected for clinical chemistry, hematology, and cytokine analysis. Clinical monitoring included heart rate, temperature, and respiratory rate. Injection of 1 dose (1g/kg) of SwIgG resulted in vomiting after injection that resolved with treatment; no other clinical signs were observed over the 3-week period. One beagle that received a single dose of 0.2g/kg SwIgG had a reaction and was removed from the second trial. The third beagle received 3 serial doses of 0.5g/kg SwIgG with no adverse reaction throughout the 3-week period. Clinical chemistry in all dogs indicated slight increase in creatine kinase activity, C-reactive protein concentration, and aspartate aminotransferase activity which returned to normal by day 7 postinjection. It is feasible to use SwIgG in dogs and additional studies to investigate its use as an adjunctive treatment for immune-mediated disorders are warranted.

Although creatine kinase (CK) is commonly used as a marker of muscle damage, there is large variability in the response to exercise. We previously found short-term immobilization blunted the rise in plasma CK after eccentric exercise, suggesting subsequent movement of damaged muscle may contribute to variability. We hypothesized that immobilization decreases lymphatic transport of CK from damaged muscle, blunting the CK response. In this study, we compared changes in plasma CK and myoglobin (Mb), as Mb is released from damaged muscle directly into the bloodstream whereas CK is released first into the lymph. Twenty-five college-age males were matched according to force loss after 50 maximal eccentric contractions of the elbow flexors and placed into an immobilization (IMM, N = 12) or control (CON, N = 13) group. IMM had their arm immobilized at 90 degrees and secured in a sling for 4 d (treatment). Venipuncture was performed during baseline, treatment, and for 5 d after treatment (recovery) to assess plasma CK activity and Mb. Urine specific gravity (USG) and muscle activity (ACT) were assessed. Immobilization significantly blunted increases in CK activity (IMM: 955 +/- 316 IU.L-1 vs CON: 2884 +/- 1083 IU.L-1; P < 0.05) but not increases in Mb (IMM: 712 +/- 278 ng.mL-1 vs CON: 891 +/- 253 ng.mL-1; P > 0.05). There were no differences in USG between groups over time (P > 0.05) and no group differences in ACT (P > 0.05). Short-term immobilization after eccentric exercise blunted the CK response but not the Mb response, suggesting lymphatic transport of CK may be responsible. Because hydration status and muscular activity after exercise were not different between groups, the blunted CK response was likely due to inactivation of CK activity before entering circulation.

The aim of this randomized double-blind placebo-controlled study was to investigate the effect of low-level laser therapy (LLLT) on markers of muscle damage (creatine kinase (CK) and strength performance) in the biceps brachii. Twenty-two physically active men were randomized into two groups: placebo and laser. All volunteers were submitted to an exercise-induced muscle damage protocol for biceps brachii (biceps curl, 10 sets of 10 repetitions with load of 50% of one-repetition maximum test (1RM)). Active LLLT (808 nm; 100 mW; 35.7 W/cm(2), 357.14 J/cm(2) per point, energy of 1 J per point applied for 10 s on four points of the biceps brachii belly of each arm) or placebo was applied between the sets of the biceps curl exercise. CK activity and maximum strength performance (1RM) were measured before, immediately after, 24, 48, and 72 h after the exercise-induced muscle damage protocol. There was an increase in CK activity after the muscle damage protocol in both groups; however, this increase was attenuated in the laser group compared to the placebo group at 72 h (placebo = 841 vs. laser = 357%; p < 0.05). Maximum strength performance was decreased immediately after the muscle damage protocol in both groups (p < 0.05), but at 24, 48, and 72 h, and it returned to the baseline level in both groups. In conclusion, the LLLT attenuated CK activity 72 h after the muscle damage protocol but did not have a positive effect on the recovery of strength performance.

During the process of endochondral bone formation, the maturing chondrocyte exhibits profound changes in energy metabolism. To explore the mechanism of energy conservation in cartilage we examined the expression of creatine kinase, an enzyme that catalyzes the formation of ATP in tissues under oxygen stress. Measurement of creatine kinase activity and cytochemical assessment of enzyme distribution clearly showed that the level of enzyme activity was related to chondrocyte maturation. Thus, as the cells hypertrophied, there was a progressive increase in creatine kinase activity. Similarly, an elevation in creatine kinase activity was noted in chondrocyte cultures as the cells assumed an hypertrophic state. When cartilage calcification was disturbed by rickets, there was a decrease in enzyme activity in the hypertrophic region. Studies were performed to examine the creatine kinase isozyme profile of cells of the epiphysis. In resting and proliferating cartilage, the isoform was MM. In hypertrophic cartilage, the predominant isoforms were MB and BB. In terms of the creatine phosphate content, the highest values were seen in the proliferative region; lower amounts were present in hypertrophic and resting cartilage; and no creatine phosphate was detected in calcified cartilage. These data suggest that turnover of creatine phosphate is greatest in the mineralized region of the epiphysis. The results of these investigations point to creatine kinase as being under developmental control. The activity of the enzyme in cartilage cells should serve as a marker of developmental events associated with chondrocyte proliferation, hypertrophy, and mineralization.

Aim: The study investigated the possible risks associated with gastrointestinal ulcer disease by evaluating the biochemical response of three body organs; heart, kidney and liver, in gastric ulcerated rats.&#x0D; Methodology: Twenty male wistar albino rats were used in the study. Gastric ulcer was induced in rats with single oral dose of 400 mg/kg body weight (b.w.) aspirin, 80 mg/kg b.w. indomethacin and 5 ml/kg b.w. acidified ethanol (40:60 v/v). Blood samples were collected into heparinized bottle and centrifuged at 4000 rpm for 10 mins to obtain the plasma. Gastric tissue, liver, kidney and heart were also collected.&#x0D; Results: Oral administration of 400 mg/kg b.w. aspirin, 80 mg/kg b.w. indomethacin and 5 ml/kg b.w. acidified ethanol caused a remarkable increase in ulcer index. There was observed a significant (p&lt;0.05) reduction in AST and ALT activities in gastric ulceration caused by aspirin (Asp), with no significant (p&lt;0.05) change in total protein (TP) concentration, lactate dehydrogenase and creatine kinase activity. However, there was increase in creatinine and urea concentration. Acidified ethanol and Indomethacin-induced ulcerated rats showed significant (p&lt;0.05) reduction in all other parameters except ALT and lactate dehydrogenase activities which did not show any significant (p&lt;0.05) change. There was also observed a significant (p&lt;0.05) increase in creatine kinase activity in indomethacin-induced ulcerated rats.&#x0D; Conclusion: Overall, the result indicates a link between gastric ulcer and organ toxicity. The use of NSAIDs above the therapeutic doses in the treatment of pains and related illness as well as excess consumption of alcohol is shown to negatively impact the stomach and cause serious damage to different body organs of wistar rats.

BackgroundMethionine is an essential amino acid for fish. The present study was conducted to investigate the effects of dietary methionine on growth performance, digestive and absorptive ability, as well as antioxidant capacity in the intestine and hepatopancreas of sub-adult grass carp (Ctenopharyngodon idella).ResultsDietary methionine deficiency significantly decreased percentage weight gain (PWG), feed intake, feed efficiency and protein efficiency ratio, as well as activities of hepatopancreatic glutamate-oxaloacetate transaminase and muscle glutamate-pyruvate transaminase in sub-adult grass carp (P < 0.05). Furthermore, methionine deficiency significantly reduced activities of trypsin, lipase and amylase in the intestine, Na+/K+-ATPase, alkaline phosphatase and γ-glutamyl transpeptidase in three intestinal segments, and creatine kinase (CK) in the proximal intestine (P < 0.05). However, an unexplained and significant increase in CK activity in the mid intestine was associated with dietary methionine deficiency. Malondialdehyde and protein carbonyl contents in the intestine and hepatopancreas were significantly increased by methionine deficiency (P < 0.05), whereas anti-hydroxyl radical capacity in the hepatopancreas and intestine, and anti-superoxide anion capacity in the intestine, were significantly decreased by methionine deficiency (P < 0.05). Moreover, methionine deficiency significantly decreased superoxide dismutase and glutathione reductase activities, glutathione contents in the hepatopancreas and intestine, as well as glutathione peroxidase activity in the intestine (P < 0.05), whereas it significantly increased activities of catalase in the hepatopancreas and glutathione-S-transferase in the hepatopancreas and intestine (P < 0.05).ConclusionsThe present results demonstrated that dietary methionine deficiency induced poor growth, and decreased digestive and absorptive function and antioxidant capacity in the hepatopancreas and intestine of sub-adult grass carp. Methionine requirements for sub-adult grass carp (450-1, 170 g) based on PWG, intestinal trypsin, and hepatopancreatic anti-hydroxyl radical activities were estimated to be 6.12 g/kg diet (21.80 g/kg protein), 6.99 g/kg diet (24.90 g/kg protein) and 5.42 g/kg diet (19.31 g/kg protein), respectively, in the presence of 1.50 g cysteine/kg (5.35 g/kg protein).

We investigated the stimulation of creatine kinase (CK) and ornithine decarboxylase (ODC) by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] in doses ranging from 1.625 to 6500 pmol in 4-week-old vitamin D-deficient chicks. Enzyme activities were monitored for 72 h. 1,25(OH)2D3 but not 24R,25(OH)2D3 enhanced the activity of ODC in duodenum and bone. The time course of ODC activity in bone was biphasic, with an increase after 1 h and a higher peak after 24 h. Diaphyses and epiphyses responded equally well after a dose of 6500 pmol. The kidney, liver, and lung showed 1.5-3.8-fold increase in CK activity following 1,25(OH)2D3, reaching a maximum between 3-5 h. However, sustained stimulation of CK activity could still be demonstrated after 72 h, and the 48-h levels in the lung even exceeded the 5-h values. No change of activity of either enzyme was noted in heart and brain after application of 1,25(OH)2D3. There was no coincidence of stimulation of ODC and CK by 1,25(OH)2D3 in the same tissue, and the dose-responsiveness of both enzymes differed considerably. Near maximum activities of ODC were achieved with 19.5 pmol 1,25(OH)2D3 in duodenum and pancreas, while maximum responses of CK occurred in the liver at 195 pmol and in lung and kidney at 6500 pmol. 24R,25(OH)2D3 failed to produce any consistent effects of either enzyme in all tissues examined. These results, particularly the lack of response to 24R,25(OH)2D3, are different from those reported in rats.

The physiological role of the phosphocreatine (PCr)/creatine kinase (CK) system has been studied in rat brain by comparing maturational changes in in vivo CK-catalyzed reaction rate and activities of CK isoenzymes. The CK-catalyzed reaction rates, measured by 31P-nuclear magnetic resonance spectroscopy, increased 4-fold between 12 and 17 days of age. The mitochondrial CK (Mi-CK) isoenzyme, as a percentage of total CK, increased to the same extent over this relatively narrow age period. Cytosolic CK (B-CK) was active earlier and, with the total CK activity, increased steadily over a longer time course. An immunohistochemical study of cerebellum showed Mi-CK predominantly in gray matter, while the cytosolic CK was present in rather large concentrations in both gray and white matter. In the molecular layer, B-CK was most prominent in the Bergmann glial cells, while Mi-CK was more prominent in Purkinje neurons. During development a redistribution of Mi-CK from the Purkinje cell bodies to their processes was observed. These results point to regional differences in CK content and in isoenzyme-specific localizations. The increase in CK activity is temporally coincident with the maturational appearance of closely coupled decreases in brain PCr and ATP during hypoxia. These maturational changes suggest that the activity of the PCr/CK system, particularly the Mi-CK isoenzyme, is central in regulation of brain ATP.

We report on a 17-year-old boy who developed a marked increase in serum creatine kinase (CK) (9743 U/l) during treatment with risperidone for catatonic psychosis. Known causes of elevated CK such as delirium, malignant neuroleptic syndrome, infection, cocaine overdose, trauma, and intramuscular injections were ruled out. Vital signs remained always within the normal range. On discontinuation of risperidone, serum CK concentrations returned to 105 U/l within 1 week and remained within normal limits. While a transient moderate increase in CK activity at admission may be related to acute psychosis, risperidone seems to be the causative agent for the later marked elevation. To our knowledge, this is the first reported case of risperidone-associated elevation of serum CK in an adolescent. While discontinuation of risperidone does not seem necessary in patients with a moderate increase of serum CK, withdrawal of neuroleptics is warranted in more severe cases.

Physical exercise or strenuous sporting activities can increase blood creatine kinase (CK) levels—something to bear in mind in patients with suspected statin-associated muscle symptoms. In their article about CK increases under statin treatment, Laufs et al. have repeatedly highlighted this important aspect (1). Nevertheless, some comments are necessary to supplement the information provided. Muscle exercise stress does not regularly “increase CK levels to 500–600 U/L“ (1); in this respect, there is considerable interindividual variability. The majority of competitive athletes have raised CK level in the blood (2). In individual cases, CK levels may occur that are clearly above 1000 U/L (3). However, some athletes show only moderate or no response (non-responders) (4). Regular preventative exercise with relatively constant muscular-mechanical stress is not often associated with CK increases. On the other hand, CK levels respond to marked changes in the amount and intensity of exercise. Thus, CK levels may increase significantly after unusual and eccentric types of exercise. This primarily applies to strength and speed-strength exercise stress (4). Therefore, taking a thorough exercise history is important to resolve issues with differential diagnosis. A cut-off CK concentration of more than 4x upper limit of normal (ULN) is of little diagnostic value. One can only agree with the authors that patients with suspected exercise-induced CK increases should observe a training break of one week. Unfortunately, competitive athletes often find it quite impossible to do this. Marked increases in CK activity in the blood are often associated with an increase in aminotransferases; here, glutamic oxaloacetic transaminase (GOT)/aspartate aminotransferase (AST)—because of its higher muscular activity—shows a stronger response compared with glutamic pyruvate transaminase (GPT)/alanine aminotransferase (ALT). Gamma-glutamyl transpeptidase (GGT) remains unchanged (3). Increases in aminotransferase levels can be expected when the creatine kinase levels exceed 3x-4x ULN.

Plasma aspartate aminotransferase and creatine kinaseactivities in thoroughbred racehorses in relation to age, sex, exercise and training