Incident depression in patients diagnosed with multiple sclerosis: a multi-database study.

BACKGROUND AND PURPOSE: Data on rates of newly diagnosed depression after multiple sclerosis (MS) diagnosis are sparse. Here, incident, treated depression in MS patients after diagnosis compared with matched non-MS patients is described. METHODS: A matched cohort study was conducted in two separate electronic medical databases: the US Department of Defense (US-DOD) military healthcare system and the UK's Clinical Practice Research Datalink GOLD (UK-CPRD). The study population included all patients with a first recorded diagnosis of MS and matched non-MS patients. Patients with a history of treated depression were excluded. Incidence rates and incidence rate ratios with 95% confidence intervals for treated depression after MS diagnosis/matched date were estimated. RESULTS: Incidence rate ratios of treated depression amongst MS patients compared with non-MS patients were 3.20 (95% confidence interval 3.05-3.35) in the US-DOD and 1.90 (95% confidence interval 1.74-2.06) in the UK-CPRD. Incidence rate ratios were elevated across age and sex. Rates were higher in females than males but, compared to non-MS patients, males with MS had a higher relative risk than females with MS. CONCLUSIONS: Multiple sclerosis patients in the UK and the USA have a two- to three-fold increased risk of new, treated depression compared to matched non-MS patients.

Infections in patients diagnosed with multiple sclerosis: A multi-database study.

BACKGROUND: Recent data on the rates of infections among patients with multiple sclerosis (MS) are sparse. The objective of this study was to quantify incidence of infections in patients with MS compared with a matched sample of patients without MS (non-MS). METHODS: This study was conducted in two separate electronic medical databases: the United States Department of Defense (US-DOD) military health care system and the United Kingdom's Clinical Practice Research Datalink GOLD (UK-CPRD). We identified patients with a first recorded diagnosis of MS between 2001 and 2016 (UK-CPRD) or 2004 and 2017 (US-DOD) and matched non-MS patients. We identified infections recorded after the MS diagnosis date (or the matched date in non-MS patients) and calculated incidence rates (IRs) and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) by infection site and type. RESULTS: Relative to non-MS patients, MS patients had higher rates of any infection (US-DOD IRR 1.76; 95% CI 1.72-1.80 and UK-CPRD IRR 1.25; 95% CI 1.21-1.29) and a two-fold higher rate of hospitalized infections (US-DOD IRR 2.43; 95% CI 2.23-2.63 and UK-CPRD IRR 2.00; 95% CI 1.84-2.17). IRs of any infection were higher in females compared with males in both MS and non-MS patients, while IRs of hospitalized infections were similar between sexes in both MS and non-MS patients. The IR of first urinary tract or kidney infection was nearly two-fold higher in MS compared with non-MS patients (US-DOD IRR 1.88; 95% CI 1.81-1.95 and UK-CPRD IRR 1.97; 95% CI 1.86-2.09) with higher rates in females compared with males. IRs for any opportunistic infection, candidiasis and any herpes virus were increased between 20 and 52% among MS patients compared with non-MS patients. IRs of meningitis, tuberculosis, hepatitis B and C were all low. CONCLUSION: MS patients have an increased risk of infection, notably infections of the renal tract, and a two-fold increased risk of hospitalized infections compared with non-MS patients.

Gene drive: progress and prospects.

Gene drive is a naturally occurring phenomenon in which selfish genetic elements manipulate gametogenesis and reproduction to increase their own transmission to the next generation. Currently, there is great excitement about the potential of harnessing such systems to control major pest and vector populations. If synthetic gene drive systems can be constructed and applied to key species, they may be able to rapidly spread either modifying or eliminating the targeted populations. This approach has been lauded as a revolutionary and efficient mechanism to control insect-borne diseases and crop pests. Driving endosymbionts have already been deployed to combat the transmission of dengue and Zika virus in mosquitoes. However, there are a variety of barriers to successfully implementing gene drive techniques in wild populations. There is a risk that targeted organisms will rapidly evolve an ability to suppress the synthetic drive system, rendering it ineffective. There are also potential risks of synthetic gene drivers invading non-target species or populations. This Special Feature covers the current state of affairs regarding both natural and synthetic gene drive systems with the aim to identify knowledge gaps. By understanding how natural drive systems spread through populations, we may be able to better predict the outcomes of synthetic drive release.

The copulatory plug delays ejaculation by rival males and affects sperm competition outcome in house mice.

Females of many species mate with multiple males (polyandry), resulting in male-male competition extending to post-copulation (sperm competition). Males adapt to such post-copulatory sexual selection by altering features of their ejaculate that increase its competitiveness and/or by decreasing the risk of sperm competition through female manipulation or interference with rival male behaviour. At ejaculation, males of many species deposit copulatory plugs, which are commonly interpreted as a male adaptation to post-copulatory competition and are thought to reduce or delay female remating. Here, we used a vertebrate model species, the house mouse, to study the consequences of copulatory plugs for post-copulatory competition. We experimentally manipulated plugs after a female's first mating and investigated the consequences for rival male behaviour and paternity outcome. We found that even intact copulatory plugs were ineffective at preventing female remating, but that plugs influenced the rival male copulatory behaviour. Rivals facing intact copulatory plugs performed more but shorter copulations and ejaculated later than when the plug had been fully or partially removed. This suggests that the copulatory plug represents a considerable physical barrier to rival males. The paternity share of first males increased with a longer delay between the first and second males' ejaculations, indicative of fitness consequences of copulatory plugs. However, when males provided little copulatory stimulation, the incidence of pregnancy failure increased, representing a potential benefit of intense and repeated copulation besides plug removal. We discuss the potential mechanisms of how plugs influence sperm competition outcome and consequences for male copulatory behaviour.

A 2.5 year study on health and locomotion symmetry in young Standardbred horses subjected to two levels of high intensity training distance.

The aim of this study was to document effects of two high-intensity training regimes on horse health. Sixteen Standardbred horses in training from September as 1-year-olds with the goal to race as 3-year-olds were used in a 2.5 year study. Horses were trained in either a control training program (C-group) or in a program with 30% reduced high intensity distance compared to the C-group (R-group). Clinical examinations were performed nine times. Locomotion asymmetry was registered with a sensor-based system 17 times. There was no difference in health scores, locomotion asymmetry or veterinary treatments between groups. Subjective lameness score and objective front limb locomotion asymmetry increased during the spring both as 2- and 3-year-olds after introduction of speed- and uphill interval training but decreased during winter. Hind limb locomotion asymmetry increased during spring as 2-year-olds and was still above initial level in December as 3-year-olds. Horses that qualified for races early had less asymmetric front limb locomotion and were less lame in clinical examinations (0.7 ± 0.3 vs. 1.6 ± 0.2 degrees [AAEP scale], P = 0.04) than late qualifiers. Days lost to training were higher in C-group than in R-group (27 ± 3% and 17 ± 3%, P = 0.029). It is concluded that (1) less days may be lost to training by reducing the high intensity training distance and (2) the introduction of new training may alter locomotion asymmetry and this can be detected with objective locomotion analysis.

Female house mice avoid fertilization by t haplotype incompatible males in a mate choice experiment.

The t haplotype in house mice is a well-known selfish genetic element with detrimental, nonadditive fitness consequences to its carriers: recessive lethal mutations cause t/t homozygotes to perish in utero. Given the severe genetic incompatibility imposed by the t haplotype, we predict females to avoid fertilization by t haplotype incompatible males. Indeed, some of the strongest evidence for compatibility mate choice is related to the t haplotype in house mice. However, all previous evidence for compatibility mate choice in this system is based on olfactory preference. It is so far unknown how general these preferences are and whether they are relevant in an actual mating context. Here, we assess female compatibility mate choice related to t haplotypes in a setting that--for the first time--allowed females to directly interact and mate with males. This approach enabled us to analyse female behaviour during the testing period, and the resulting paternity success and fitness consequences of a given choice. We show that genetic incompatibilities arising from the t haplotype had severe indirect fitness consequences and t females avoided fertilization by t incompatible males. The results are inconclusive whether this avoidance of t fertilization by t females was caused by pre- or post-copulatory processes.

Causes of male sexual trait divergence in introduced populations of guppies.

Males from different populations of the same species often differ in their sexually selected traits. Variation in sexually selected traits can be attributed to sexual selection if phenotypic divergence matches the direction of sexual selection gradients among populations. However, phenotypic divergence of sexually selected traits may also be influenced by other factors, such as natural selection and genetic constraints. Here, we document differences in male sexual traits among six introduced Australian populations of guppies and untangle the forces driving divergence in these sexually selected traits. Using an experimental approach, we found that male size, area of orange coloration, number of sperm per ejaculate and linear sexual selection gradients for male traits differed among populations. Within populations, a large mismatch between the direction of selection and male traits suggests that constraints may be important in preventing male traits from evolving in the direction of selection. Among populations, however, variation in sexual selection explained more than half of the differences in trait variation, suggesting that, despite within-population constraints, sexual selection has contributed to population divergence of male traits. Differences in sexual traits were also associated with predation risk and neutral genetic distance. Our study highlights the importance of sexual selection in trait divergence in introduced populations, despite the presence of constraining factors such as predation risk and evolutionary history.

Growth, training response and health in Standardbred yearlings fed a forage-only diet.

The aim of this study was to, from a holistic perspective, describe the effects of a forage-only feeding system and a conventional training program on young Standardbred horses and compare data with similar observations from the literature. Sixteen Standardbred colts fed a forage-only diet for 4 months from breaking (August to December) and with the goal to vigorously trot 5 to 7 km at a speed of 5.6 m/s (3 min/km) were studied. The horses were fed grass haylage (56 to 61% dry matter (DM), 2.80 to 3.02 Mcal DE/kg DM and 130 to 152 g CP/kg DM) ad libitum, 1 kg of a lucerne product and minerals. The amount of training and number of training sessions were documented daily, and feed intake and body development were measured once every month. Heart rate (HR) was measured during and after a standardized exercise test in October and December. In December, a postexercise venous blood sample was collected and analyzed for plasma lactate concentration. Muscle biopsies (m. gluteus medius) were taken and analyzed for glycogen and fiber composition. Health was assessed in October and November by an independent veterinarian using a standardized health scoring protocol. BW and height at withers increased from 402 to 453 kg (root mean square error (RMSE) 6) and from 148.7 to 154.1 cm (RMSE 0.7), respectively, and the body condition score was 4.9 (RMSE 0.2) at the end of the study. Muscle glycogen content was 532 mmol/kg dry weight (s.d. 56). There was a significant decrease in postexercise HR (81 v. 73 bpm, RMSE 8), and the individual amount of training was negatively correlated with HR during and after exercise. Health scores were high and similar at both assessments (8.4 and 8.4 (RMSE 1.0) out of 10; P > 0.05), and the number of lost training days per month due to health problems was <0.9, with the exception of November (5.3 days). It is concluded that yearlings in training fed high-energy forage ad libitum can reach a conventional training goal and grow at least as well as earlier observations on yearlings of other light breeds.

Genes or culture: are mitochondrial genes associated with tool use in bottlenose dolphins (Tursiops sp.)?

Some bottlenose dolphins use marine sponges as foraging tools ('sponging'), which appears to be socially transmitted from mothers mainly to their female offspring. Yet, explanations alternative to social transmission have been proposed. Firstly, the propensity to engage in sponging might be due to differences in diving ability caused by variation of mitochondrial genes coding for proteins of the respiratory chain. Secondly, the cultural technique of sponging may have selected for changes in these same genes (or other autosomal ones) among its possessors. We tested whether sponging can be predicted by mitochondrial coding genes and whether these genes are under selection. In 29 spongers and 54 non-spongers from two study sites, the non-coding haplotype at the HVRI locus was a significant predictor of sponging, whereas the coding mitochondrial genes were not. There was no evidence of selection in the investigated genes. Our study shows that mitochondrial gene variation is unlikely to be a viable alternative to cultural transmission as a primary driver of tool use in dolphins.

Experimental evidence that high levels of inbreeding depress sperm competitiveness.

The effects of inbreeding on sperm quantity and quality are among the most dramatic examples of inbreeding depression. The extent to which inbreeding depression results in decreased fertilization success of a male's sperm, however, remains largely unknown. This task is made more difficult by the fact that other factors, such as cryptic female choice, male sperm allocation and mating order, can also drive patterns of paternity. Here, we use artificial insemination to eliminate these extraneous sources of variation and to measure the effects of inbreeding on the competitiveness of a male's sperm. We simultaneously inseminated female guppies (Poecilia reticulata) with equal amounts of sperm from an outbred (f = 0) male and either a highly (f = 0.59) or a moderately inbred (f = 0.25) male. Highly inbred males sired significantly fewer offspring than outbred males, but share of paternity did not differ between moderately inbred and outbred males. These findings therefore confirm that severe inbreeding can impair the competitiveness of sperm, but suggest that in the focal population inbreeding at order of a brother-sister mating does not reduce a male's sperm competitiveness.

The opioid haemorphin-7 in horses during low-speed and high-speed treadmill exercise to fatigue.

The opioid neuropeptide haemorphin-7 was measured, by immunoreactivity, in Standardbred horses during low-speed (7 m/s) and high-speed (10 m/s) endurance exercises, lasting 49-58 and 12-16 min respectively. In parallel, heart rate, muscle temperature and plasma lactate concentrations were measured. The profile of the low-speed exercise showed significantly increased heart rate after 10 min [154 beats per minute (bpm)]. After the exercise, muscle temperature (42.1 degrees C) and plasma lactate (4.8 mmol/l) were significantly increased. The profile of the high-speed exercise was comparatively characterized by a higher increase of heart rate after 5 min (194 bpm) and higher increases of muscle temperature (43.2 degrees C) and lactate levels (15.8 mmol/l) after the exercise. The horses were probably exhausted by glycogen depletion in the low-speed exercise and by muscle pH decrease in the high-speed exercise. Haemorphin-7 increased significantly during the high-speed exercise (274.8 fmol/ml) but not during low speed (108.3 fmol/ml), coincident with the results of lactate. These results suggest that plasma haemorphin-7 is measurable in the horse by immunoreactivity, and that intense exercise stimulates release of this opioid. Such endogenous opioids are most likely involved in regulatory functions associated with pain, physical effort, inflammation, and blood pressure variation in horses, as have been established in other species.

Hypoglycaemia with insulin aspart: a double-blind, randomised, crossover trial in subjects with Type 1 diabetes.

AIMS: To compare the effects of the rapid-acting insulin analogue insulin aspart and soluble human insulin on hypoglycaemia and glycaemic control in patients with Type 1 diabetes when injected immediately before meals as part of intensive insulin therapy. METHODS: In this multinational, double-blind, randomised, crossover trial, 155 patients with Type 1 diabetes (HbA(1c) < 8.0%) were symmetrically randomised to two 16-week treatment periods on either type of insulin, both injected 0-5 min before meals. NPH insulin was given as basal insulin once or twice daily as needed, and insulin dosages were regularly adjusted using pre-defined algorithms to maintain tight glycaemic control. Treatment periods were separated by a 4-week washout. RESULTS: The rate of major nocturnal (24.00-06.00 h) hypoglycaemic episodes was 72% lower with insulin aspart than with human insulin (0.067 vs. 0.225 events/month; P = 0.001). Total rate of major hypoglycaemia did not differ significantly between treatments (insulin aspart/human insulin relative risk 0.72; 95% CI 0.47-1.09, P = 0.12). The rate of minor events was significantly reduced by 7% with insulin aspart (P = 0.048). Reductions in rate of hypoglycaemia were achieved with maintained overall glycaemic control: Mean HbA(1c) remained constant, slightly below 7.7% on both treatments. CONCLUSIONS: The use of insulin aspart in an intensive insulin regimen in patients with tightly controlled Type 1 diabetes led to clinically significant reductions in major nocturnal hypoglycaemia with no deterioration in glycaemic control. Major nocturnal hypoglycaemia appears to be a strong clinical indication for the use of rapid-acting insulin analogues during intensive insulin therapy.

Extreme polymorphism in a Y-linked sexually selected trait.

Males of the livebearing fish, Poecilia parae, exhibit one of the most complex polymorphisms known to occur within populations, whereas females are monomorphic. We describe five distinct male colour morphs and an associated size dimorphism, and demonstrate through pedigree analysis that the locus or loci controlling the male colour polymorphism is linked to the Y-chromosome. Field surveys from 1999 to 2002 of nine populations in Guyana and Suriname, South America, indicate that some morphs are consistently abundant and others are rare, implying that the colour polymorphism has important fitness consequences. By rearing offspring of field-inseminated females, we showed that the common morph is also the most successful morph in terms of reproduction. However, dichotomous choice tests show that two rare morphs are preferred by females over the common morph. These results suggest that alternative male mating strategies, sperm competition, overt male-male competition, or other processes are overriding female preferences in these populations. Furthermore, Y-linkage of the colour polymorphism in P. parae supports the hypothesis that heterogametic sex chromosomes harbour sexually antagonistic traits beneficial to the heterogametic sex.

Comparison of thrice daily 'high' vs. 'medium' premixed insulin aspart with respect to evening and overnight glycaemic control in patients with type 2 diabetes.

BACKGROUND: The glycaemic control of thrice daily treatment with premixed biphasic insulin aspart (BIAsp) without other antidiabetic therapy was tested in type 2 diabetic patients, in order to compare the glucose control of a 'high' mixture (BIAsp 70) or a 'medium' mixture (BIAsp 50) (70 or 50% soluble IAsp and 30 or 50% protamine-crystallized IAsp, respectively) administered just before dinner. AIM: To compare these regimens to conventional 30 : 70 premixture on a twice a day basis. METHODS: This randomized, double-blind, two-period crossover study included 16 patients with type 2 diabetes. Twenty four-hour serum glucose and insulin profiles were obtained thrice: (1) after a one-week run-in period with biphasic human insulin (BHI) 30/70 twice daily (run-in), (2) after 4 weeks of treatment with thrice daily BIAsp 70 before breakfast, lunch and dinner (Dinner70 regimen) and (3) after 4 weeks of BIAsp 70 before breakfast and lunch and BIAsp 50 before dinner (Dinner50). RESULTS: Daytime average serum glucose was lower with Dinner70 compared to run-in (9.6 +/- 0.39 mmol/l vs. 11.2 +/- 0.61 mmol/l, p < 0.05). Postprandial glucose excursions after breakfast and lunch were lower, but fasting morning glucose was higher during the treatment periods than in the run-in period. Twenty four-hour C-peptide AUC was considerably lower during both treatment periods than in the run-in period (run-in/Dinner50 ratio 1.29 [1.08; 1.54] p < 0.01; run-in/Dinner70 ratio 1.31 [1.08;1.58], p < 0.01). CONCLUSIONS: Switching the dinner dose to BIAsp 50 did not alter overall glucose control significantly from that provided with BIAsp 70. Exploratory analyses between the two active treatment regimens and run-in/BHI indicate that thrice daily BIAsp 70 administration: (1) for optimization of the night-time control, the dinner dose needs adjustment or replacement by a premixed insulin with a larger proportion of basal insulin than BIAsp 50 and (2) none of the premixtures adequately provide for both the evening meal and overnight requirements.

A randomized trial of insulin aspart with intensified basal NPH insulin supplementation in people with Type 1 diabetes.

AIMS: Insulin aspart has been shown to improve post-prandial and overall glycaemic control in people with Type 1 diabetes. We hypothesized that insulin aspart with intensified basal NPH insulin supplementation would result in better overall glycaemic control than human regular insulin with standard basal NPH insulin. METHODS: The trial was conducted in 43 centres in seven countries. People with Type 1 diabetes were randomized to mealtime insulin aspart with up to four daily NPH doses if meals were > 5 h apart and a 25% increase in bedtime NPH dose (n = 187), or to mealtime human unmodified insulin with once or twice daily basal NPH insulin (n = 181). Efficacy and safety were evaluated at 12 weeks (primary evaluation period) and 64 weeks. RESULTS: At 12 and 64 weeks there was no statistically significant difference in HbA1c between the insulin aspart and regular insulin groups: -0.09 (95% confidence interval (CI) -0.23, +0.05)% and -0.14 (-0.32, +0.04)%. Post-prandial glucose values were lower and the area under the 24-h self-monitored blood glucose curve above 7.0 mmol/l was 28% smaller with insulin aspart (35.2 +/- 3.2 vs. 48.9 +/- 3.1 mmol/l h, P = 0.0015). No significant differences were found in mild or severe hypoglycaemia, or adverse event rate. At 64 weeks treatment satisfaction was higher in the insulin aspart group (difference 1.57 (95% CI 0.49, 2.64) points, P = 0.004), while quality of life was not different. CONCLUSIONS: Improved post-prandial glycaemic control and treatment satisfaction with insulin aspart were confirmed. Intensifying basal insulin supplementation resulted in a similar HbA1c decrement as previously found with the use of insulin aspart and standard NPH insulin supplementation. This does not support routinely basal NPH insulin intensification when using rapid-acting insulin analogues in daily practice.

Effects on exercise metabolism of varying dietary starch and sugar proportions.

Studies of the effect of varying dietary carbohydrate compositions on exercise metabolism of horses are scarce. In the present study, the starch and sugar proportions were altered in the diet to 4 Standardbred horses. In a crossover experiment, the horses were offered a hay and oat diet, where the oats were substituted for barley syrup (BS) at 4 levels (BS 0, 0.5, 1.0 and 1.5 kg). Each diet was consumed for 21 days and both an incremental treadmill exercise test (IE) and a 40 min submaximal exercise test (SE) were performed. During the IE there was a significant (P<0.05) increase in mean VO2 on BS 1.5 and at the highest speed respiratory exchange ratio (RER) was significantly lower on BS 1.0 and 1.5. During the SE, RER and HR were significantly higher on BS 1.0 and 1.5. There were no significant effects of diets on plasma levels of glucose, lactate and insulin. Following the SE there was a significant decrease in the muscle glycogen content on BS 0, which was not observed in the other diets. In addition, there was a numerical decrease in the glycogen utilisation with increasing proportions of sugar in the diet. In conclusion, this study indicates that horses on diets with a high sugar inclusion respond with an increased heart rate during exercise of lower intensities; and that the response in VO2 and RER may differ depending on the exercise intensity. In addition, glycogen utilisation during submaximal exercise was lowered when daily sugar intake was increased. However, further investigation is needed to evaluate whether this strategy of feeding could be beneficial for exercising horses competing over endurance distances.

Clinical effects of betamethasone and hyaluronan, and of defocalized carbon dioxide laser treatment on traumatic arthritis in the fetlock joints of horses.

The clinical effects of intra-articular betamethasone together with hyaluronan (betaM/HA) and treatment with a defocalized carbon dioxide laser on acute traumatic arthritis of the fetlock joint were assessed. The horses in these studies were selected using a thorough lameness examination, including intra-articular anaesthesia abolishing the lameness. This investigation comprised an observer-blind study, including 10 sport horses (10 joints), and a prospective study, including 180 sport horses (333 joints). In both studies, the material was divided into two groups treated with either betaM/HA or a carbon dioxide laser. The treatment doses were 12 mg of betaM, 20 mg of HA or 60 J/cm2 of treated area. Convalescence before training was 21 days for both groups in the observer-blind study. In the prospective study, convalescence in the betaM/HA group was 21 days but was only 7 days for the laser-treated group. In the observer-blind study, three of five treated joints recovered in both cohorts. In the prospective study, the groups had significantly different recovery rates--68% of the betaM/HA-treated joints and 80% of the carbon dioxide laser-treated joints. These results indicate that the defocalized carbon dioxide laser should be an applicable mode of treatment of acute traumatic synovitis in horses. However, the biochemical functions related to carbon dioxide laser treatment require further elucidation.

Premixed insulin aspart 30 vs. premixed human insulin 30/70 twice daily: a randomized trial in Type 1 and Type 2 diabetic patients.

AIM: To compare the efficacy and safety of premixed insulin aspart (30% free and 70% protamine-bound, BIAsp 30) with human insulin premix (BHI 30) used in a twice-daily injection regimen in people with Type 1 and Type 2 diabetes. METHODS: People with Type 1 and Type 2 diabetes (n = 294) using twice-daily insulin were randomized to a 12-week open-label comparison of BIAsp 30 and BHI 30. Efficacy was assessed by analysis of variance of 12-week data, adjusted for baseline level. RESULTS: BIAsp 30 was as effective as BHI 30 based on the primary efficacy measure, HbA1c, mean difference -0.01 (90% confidence interval (CI) -0.14; 0.12) %Hb. Meal-time self-measured blood glucose increment averaged over the three main meals was significantly lower in the BIAsp 30 group than in the BHI 30 group (-0.68 (-1.20; -0.16) mmol/l; P < 0.02). Significant improvements were observed after breakfast, before lunch, after dinner and at bedtime (P < 0.02-0.05), with blood glucose around 1.0 mmol/l lower in the BIAsp 30 group. The number of major hypoglycaemic episodes with BIAsp 30 was half that with BHI 30. However, the overall risk of both minor and major hypoglycaemia did not differ significantly between treatments. CONCLUSION: Post-prandial glycaemic control was significantly improved, without increasing the risk of hypoglycaemia, and overall control was similar when people with Type 1 and Type 2 diabetes were treated on a twice-daily regimen with immediate premeal injections of BIAsp 30 compared with BHI 30.

Water intake and fluid shifts in horses: effects of hydration status during two exercise tests.

In the present study, the main objective was to study factors affecting postexercise voluntary water intake in horses. Four Standardbred horses (mean +/- s.e. bwt 500 +/- 8 kg) were used to study water intake and effects of altering hydration status before an incremental exercise test (INCR) and a 40 min constant velocity exercise test (CONST) on a treadmill. Exercise was performed during normohydration (N), after dehydration for 24 h (DEH) and after hyperhydration with 12 l water 30 min before exercise (HH). DEH resulted in a bodyweight loss of 3% and there were signs of some fluid uptake prior to exercise in both HH trials. By the end of the INCR, the calculated change in plasma volume (PVcalc) was -13 +/- 1, -21 +/- 1 and -11 +/- 3% in the N, DEH and HH trials, respectively. During the highest exercise velocities a hypotonic shift of fluid was seen in all INCR trials. There was a greater accumulation of plasma lactate (pLA) in HH-than in N-INCR, probably caused by the extra weight to be carried. CONST induced a similar fluid loss (3%) in all trials, but the decrease in PVcalc at the end of exercise was significantly smaller in HH (-7 +/- 2%) than in N (-14 +/- 1%) and DEH (-19 +/- 2%). In DEH-INCR and DEH-CONST, plasma sodium concentration (pNa) was higher than in N until drinking water was offered 1 h postexercise. In the presence of both an increased pNa and a decrease in PVcalc when dehydrated, the horses drank immediately when offered water postexercise. In N-CONST, there was a significant decrease in calculated PVcalc (-10 +/- 2%) but no increase in pNa when water was given and in this trial the horses rehydrated less rapidly. Plasma aldosterone concentration (PAC) had increased to the same magnitude in all trials after about 10 min, irrespective of type of exercise or hydration status. It was concluded that when both an osmotic and hypovolemic thirst stimulus was present, the horses rehydrated more rapidly postexercise.

Effects of acute intravenous aldosterone administration on Na(+), K(+), and water excretion in the horse.

The effect of a temporary increase in plasma aldosterone concentration on Na(+), K(+), and water balance was investigated in four horses. Aldosterone was injected intravenously for 6 h at 20-min intervals (total 5.4 microg/kg body wt). Samples were taken for 24 h before, during, and for 48 h after the treatment. Aldosterone treatment reduced the Na(+) loss via urine and feces by 99 and 72%, respectively, later followed by a marked increase in Na(+) excretion by both pathways. During the first 6 h after the treatment, fecal K(+) excretion was elevated, and the plasma K(+) concentration was lowered. Fluid was retained throughout the treatment period and for 12-15 h thereafter. In a second experiment, exercise was performed once after aldosterone treatment and once without prior treatment. Sweat samples were collected, and the composition was not altered after treatment. It was concluded that acute aldosterone injections reduce Na(+) losses in both feces and urine but not in sweat. In addition, the feces was shown to be the main excretion pathway of aldosterone.