Investigations into a trigger-based approach for initiating emergency vaccination to augment stamping out of foot-and-mouth disease in New Zealand: a simulation study.

AIMS: To investigate an adaptive management approach to the deployment of emergency vaccination as an additional measure to stamping out (SO) during simulated outbreaks of foot-and-mouth disease (FMD) in New Zealand. METHODS: A simulation modelling (n=6000 simulations) approach was used. The study population comprised all known farms in New Zealand with FMD-susceptible livestock. Each simulation started with infection seeded into a single randomly selected farm. Each outbreak was randomly assigned to one of four control strategies, comprising SO only; trigger-based vaccination (TRV) where SO was augmented with vaccination if an early decision indicator trigger operating between Days 11-35 of the response indicated a large outbreak was developing; SO plus vaccination started randomly on Days 11-35 of the response (VACr); and SO plus vaccination with a fixed start on Day 21 of the response (VACf). Other parameters, such as the number of personnel available were also varied randomly. Generalised additive models (GAM) were used to evaluate variables associated with the number of infected premises (IP) and epidemic duration. RESULTS: The mean number of IP was 29 (median 9, min 1, max 757), while epidemics lasted on average 26.9 (median 18, min 1, max 220) days. These excluded 303 extreme outbreaks larger than the UK 2001 FMD epidemic (2,030 cases). Univariable analysis of the pooled vaccination results vs. SO, showed that vaccination significantly reduced the number of IP (p<0.001) and outbreak duration (p<0.001). GAM of large outbreaks revealed that only the TRV strategy was significantly protective compared to SO alone, reducing the odds of a large outbreak by 22% (OR=0.78; 95% CI=0.63-0.96). The number of veterinarians was non-linearly associated with large outbreaks, with low numbers increasing the odds of a large outbreak, but above 200 veterinarians, the odds reduced. Time to first detection was also non-linearly associated with large outbreaks, with detections <13 days protective and longer detection times increasing the odds of a large outbreak. GAM of long outbreaks showed similar findings, except that all three vaccination strategies significantly reduced duration. Overall, the TRV strategy resulted in the smallest and shortest epidemics. CONCLUSIONS AND CLINICAL RELEVANCE: An adaptive management approach that deployed vaccination in response to a trigger when a large outbreak was developing outperformed SO and reduced the odds of large or long outbreaks more than the other two vaccination strategies, although the differences between the three vaccination strategies were statistically small. This study provides highly relevant insights into the dynamics of disease establishment and spread that will guide New Zealand's readiness for responding to highly infectious disease incursions such as FMD.

Prevalence and characterisation of wounds in sheep attributed to attacks by kea (Nestor notabilis) on high country farms in New Zealand.

Aims: To characterise and classify wounds in sheep suspected to have been caused by attacks by kea (Nestor notabilis) (kea strike), and to report the prevalence of these wounds on five high country farms in the South Island of New Zealand.Methods: Data were collected from farms between 28 August 2012 and 20 September 2013. Sheep were examined opportunistically immediately after shearing for signs of wounds caused by kea. The age and sex of sheep were also recorded. Wounds were measured and characterised as recent, healing, or healed, and the estimated true prevalence was calculated for each farm.Results: Injuries consistent with kea strike wounds were identified in 70/13,978 (0.5%) sheep examined. The estimated true prevalence varied between farms, from 0 (95% CI = 0-0.16) to 1.25 (95% CI = 0.97-1.61)%. Of the 76 wounds identified, 61 (80%) were located in the lumbar region, and 74 (97%) consisted of full-thickness ulceration of the skin, one showed evidence of injury to muscle and one to bone. The median length of the 63 wounds measured was 6 (min 1, max 23.5) cm, and 10/63 (13%) were categorised as recently healed, 47/63 (62%) as healing, and 17/63 (22%) as recent wounds.Conclusions: The results of this study show that kea strike on sheep was occurring at a low prevalence on the high country farms surveyed. The wounds identified were survivable, but the welfare impact of kea strike on sheep should be considered in balance with the conservation status of kea. There was clear variation in the prevalence of wounds attributed to kea strike between the farms but we were not able to identify the risk factors contributing to these differences. Future studies of kea strike should examine variables such as altitude, local kea density and distribution, and differences in kea strike management and husbandry practices, and should include high country farms without a history of kea strike.

Prevalence of Candidatus Mycoplasma haemolamae, bovine viral diarrhoea virus, and gastrointestinal parasitism in a sample of adult New Zealand alpaca (Vicugna pacos).

AIM: To determine the prevalence of infection with Candidatus Mycoplasma haemolamae (Mhl), antibodies to bovine viral diarrhoea virus (BVDV), and BVDV antigen, and the prevalence of animals with elevated faecal nematode egg counts (FEC) in a sample of adult New Zealand alpaca (Vicugna pacos). METHODS: Blood samples were obtained from 175 alpaca, collected from 15 farms around New Zealand, and from 31 samples sent to a diagnostic laboratory for routine haematology. Blood smears (n=170) were examined microscopically for the presence of haemoplasma, and DNA was extracted from whole blood (n=206) for real-time PCR testing for Mhl. Packed cell volume (PCV) was determined for 193 samples. Serum samples (n=195) were tested for BVDV antibody using ELISA, and for BVDV antigen using a real-time PCR assay. Faecal samples were collected from 143 animals; FEC were measured, and samples pooled for larval culture. RESULTS: No haemoplasma organisms were present on blood smear examination. Of the 206 blood samples, two (from the same farm) were positive for Mhl by real-time PCR testing, giving a prevalence of infection with Mhl of 0.97%. Of the 195 serum samples tested, four (2.1%) were positive for antibodies to BVDV; animals with BVDV antibodies were from 3/15 (20%) farms, none of which farmed cattle. None of the serum samples were positive by PCR for BVDV antigen. The median FEC was 50 epg (min 0, max 4,700), with 55/143 (38.5%) samples having 0 epg, and 33/143 (23.1%) having ≥250 epg. Haemonchus spp. were the most common nematodes present in faecal larval cultures from the North Island. Log10 FEC was negatively associated with PCV (p=0.02), and was higher in males than females (p<0.001), and in animals that were positive compared with negative for Mhl (p=0.022). CONCLUSIONS AND CLINICAL RELEVANCE: The number of alpaca infected with Mhl was low, as was the seroprevalence of BVDV. Gastrointestinal parasitism was, however, a common finding in this sample of New Zealand alpaca.

The assessment of the serum C-peptide and plasma glucose levels by orally administered whey proteins in type 2 diabetes mellitus.

A personalized antidiabetic therapy is not yet part of the official guidelines of professional societies for clinical practice. The aim of this study was to evaluate the serum C-peptide and plasma glucose levels in patients with type 2 diabetes mellitus (T2DM) after oral administration of whey proteins. Sixteen overweight T2DM Caucasians with good glycemic control and with preserved fasting serum C-peptide levels (>200 nmol/l) were enrolled in this study. Two oral stimulation tests - one with 75 g of glucose (OGTT) and the other with 75 g of whey proteins (OWIST) - were administered for assessing serum C-peptide and plasma glucose levels in each participant. Both oral tests induced similar pattern of C-peptide secretion, with a peak at 90 min. The serum C-peptide peak concentration was 2.91+/-0.27 nmol/l in OWIST, which was 22 % lower than in OGTT. Similarly, the C-peptide iAUC(0-180) were 32 % lower in the OWIST than in the OGTT (p<0.01). Contrary to OGTT the OWIST did not cause a significant increase of glycemia (p<0.01). Our study showed that the OWIST represents a useful tool in estimation of stimulated serum C-peptide levels in patients with T2DM.

Glucagon-like peptide-1 analogues exenatide and liraglutide exert inhibitory effect on the early phase of liver regeneration after partial hepatectomy in rats.

Glucagon-like peptide-1 (GLP-1) is an incretin known for proliferative and antiapoptotic effects on various tissues. Exenatide and Liraglutide are GLP-1 analogues used in clinical practice as antidiabetic drugs. Since GLP-1 and its analogues exert significant effect on liver metabolism and since changes in intermediary metabolism play an important role in the process of liver regeneration, we decided to determine the effect of Exenatide and Liraglutide on the early phase of liver regeneration and selected metabolic parameters in a model of 2/3 partial hepatectomy (PHx) in rats. Animals were submitted either to PHx or laparotomy and received 3 doses of either GLP-1 analogues (Exenatide - 42 microg/kg b.w., Liraglutide - 0.75 mg/kg b.w.) or saline intraperitoneally. We analyzed body and liver weight, liver bromodeoxyuridine incorporation, liver content of DNA, triacylglycerols and cholesterol and biochemical serum parameters. Bromodeoxyuridine labeling was significantly lower in hepatectomized rats receiving either type of GLP-1 analogues when compared to hepatectomized controls. This effect was more pronounced in the Liraglutide group compared to Exenatide (p<0.001). In addition, liver DNA content was lower in hepatectomized rats receiving Liraglutide than in hepatectomized control rats (p<0.001). In conclusion, GLP-1 analogues Exenatide and Liraglutide significantly inhibited an early phase of liver regeneration after PHx in rats. This inhibitory effect was more pronounced in rats receiving Liraglutide.

Chronic dietary exposure to branched chain amino acids impairs glucose disposal in vegans but not in omnivores.

BACKGROUND/OBJECTIVES: Branched chain amino acids (BCAA) are among nutrients strongly linked with insulin sensitivity (IS) measures. We investigated the effects of a chronic increase of BCAA intake on IS in two groups of healthy subjects differing in their basal consumption of BCAA, that is, vegans and omnivores. SUBJECTS/METHODS: Eight vegans and eight matched omnivores (five men and three women in each group) received 15 g (women) or 20 g (men) of BCAA daily for 3 months. Anthropometry, blood analyses, glucose clamp, arginine test, subcutaneous abdominal adipose tissue (AT) and skeletal muscle (SM) biopsies (mRNA levels of selected metabolic markers, respiratory chain (RC) activity) were performed at baseline, after the intervention and after a 6 month wash-out period. RESULTS: Compared with omnivores, vegans had higher IS at baseline (GIR, glucose infusion rate: 9.6±2.4 vs 7.1±2.4 mg/kg/min, 95% CI for difference: 0.55 to 5.82) that declined after the intervention and returned to baseline values after the wash-out period (changes in GIR with 95% CI, 3-0 months: -1.64 [-2.5; -0.75] and 9-3 months: 1.65 [0.75; 2.54] mg/kg/min). No such change was observed in omnivores. In omnivores the intervention led to an increased expression of lipogenic genes (DGAT2, FASN, PPARγ, SCD1) in AT. SM RC activity increased in both groups. CONCLUSIONS: Negative impact of increased BCAA intake on IS was only detected in vegans, that is, subjects with low basal amino acids/BCAA intake, which appear to be unable to induce sufficient compensatory changes within AT and SM on a BCAA challenge.

Evaluating the benefits of vaccination when used in combination with stamping-out measures against hypothetical introductions of foot-and-mouth disease into New Zealand: a simulation study.

AIMS: To evaluate the benefits of vaccination against simulated outbreaks of foot-and-mouth disease (FMD) in New Zealand, when applied as an additional measure to stamping-out. METHODS: A simulation modelling approach was used. The study population comprised all known farms in New Zealand with FMD-susceptible livestock. Infection was seeded into three different areas of New Zealand. Transmission mechanisms included direct and indirect contacts, local spread and airborne spread. Efficacies of some of the stamping-out measures were varied. Vaccination strategies involved different start times, size and type of vaccination zone, and species vaccinated. Personnel resources for vaccination were varied as was the herd immunity profile following vaccination. Altogether, 336 models were specified, with 100 iterations conducted for each model. Generalised linear modelling and boosted regression trees were used to evaluate which variables had the biggest effect on the number of infected premises (IP), epidemic duration and area under control. RESULTS: Vaccination, when used as an adjunct to the standard stamping-out programme, significantly reduced the outbreak size. Vaccination reduced the median number of IP by 26 (95% CI=18-35), epidemic duration by 16 (95% CI=13-19) days and area under control by 474 (95% CI=250-699) km2 when there was no airborne spread; and when there was airborne spread the median reduction was 87 (95% CI=70-105) IP, 32 (95% CI=28-35) days and 898 (95% CI=665-1139) km2, respectively. Multivariable analyses showed that starting vaccination 11 days after first detection of FMD produced greater benefits than starting 16 or 21 days after detection. Increasing vaccination zones resulted in increased benefits. Boosted regression tree analyses showed that the most influential variables on the outcome measures were interval to first detection, incursion location, whether there was airborne spread or not and herd immunity profile. CONCLUSIONS AND CLINICAL RELEVANCE: This study showed that there are benefits to the use of vaccination in combination with a stamping-out policy for control of FMD outbreaks under New Zealand conditions. The optimal vaccination strategy was identified as being a 3-5 km radius suppressive vaccination zone deployed between 11-16 days after first detection. Vaccination had a greater benefit during larger outbreaks, such as when there was airborne transmission. The key factors which were identified from this study will help inform New Zealand's competent authority on how best to deploy vaccination to further strengthen its approach to FMD eradication should New Zealand ever experience an outbreak.

Investigation of bovine haemoplasmas and their association with anaemia in New Zealand cattle.

CASE HISTORY AND CLINICAL FINDINGS: A dairy cow, from a herd in the Waikato region of New Zealand, was reported with regenerative anaemia on 12 September 2014. Testing of blood from the animal using PCR assays for Theileria orientalis produced a negative result for both Chitose and Ikeda types. LABORATORY FINDINGS: Using PCR and DNA sequencing, blood from the cow was positive for Candidatus Mycoplasma haemobos. Further testing of another 12 animals from the case herd, 27 days after the affected cow was first reported, showed 11 animals were positive for Candidatus M. haemobos or Mycoplasma wenyonii in the PCR. None of these cattle were clinically anaemic or positive for T. orientalis Ikeda type using PCR. A convenience sample of 47 blood samples from cattle throughout New Zealand, submitted to the Investigation and Diagnostic Centre (Ministry for Primary Industries) for surveillance testing for T. orientalis Ikeda, was selected for further testing for bovine haemoplasmas. Of these samples, 6/47 (13%) and 13/47(28%) were positive for M. wenyonii and Candidatus M. haemobos, respectively. There was no difference in the proportion of samples positive for the bovine haemaplasmas between cattle with anaemia that were negative for T. orientalis (6/20, 33%), or without anaemia or T. orientalis (10/18, 56%), or from cattle herds experiencing anaemia and infection with T. orientalis Ikeda type (3/9, 33%). DIAGNOSIS: Bovine haemoplasmosis. CLINICAL RELEVANCE: The presence of bovine haemoplasmas in blood does not establish causality for anaemia in cattle. Diagnosis of anaemia associated with haemoplasmosis would require exclusion of other causes of regenerative anaemia and an association of the agent with anaemia in affected cattle herds. The data collected in this study did not provide evidence that bovine haemoplasmas were associated with a large number of outbreaks of anaemia in cattle in New Zealand.

Excess of free fatty acids as a cause of metabolic dysfunction in skeletal muscle.

Obesity is often associated with metabolic impairments in peripheral tissues. Evidence suggests an excess of free fatty acids (FFA) as one factor linking obesity and related pathological conditions and the impact of FFA overload on skeletal muscle metabolism is described herein. Obesity is associated with dysfunctional adipose tissue unable to buffer the flux of dietary lipids. Resulting increased levels and fluxes of plasma FFA lead to ectopic lipid deposition and lipotoxicity. FFA accumulated in skeletal muscle are associated with insulin resistance and overall cellular dysfunction. Mechanisms supposed to be involved in these conditions include the Randle cycle, intracellular accumulation of lipid metabolites, inflammation and mitochondrial dysfunction or mitochondrial stress. These mechanisms are described and discussed in the view of current experimental evidence with an emphasis on conflicting theories of decreased vs. increased mitochondrial fat oxidation associated with lipid overload. Since different types of FFA may induce diverse metabolic responses in skeletal muscle cells, this review also focuses on cellular mechanisms underlying the different action of saturated and unsaturated FFA.

Network analysis of wildlife translocations in New Zealand.

AIMS: To identify network measures with relevance to disease spread in a network of movements derived from the Department of Conservation (DOC) translocation records from 1970 to mid-2014, and to identify conservation sites that should be prioritised for surveillance activities and improvements to data collection to make the best use of network analysis techniques in the future. METHODS: Data included the source and destination of translocated specimens, the species and the dates the translocations were expected to occur. The data were used to construct a directed, non-weighted network in which a translocation event represented a tie in the network. Network density, in-degree (movements entering a node of interest) and out-degree (movements leaving a node of interest) and reciprocity were calculated. RESULTS: The data analysed consisted of 692 unique translocations between 307 sites, with the majority (518; 73%) being for birds. The constructed network for bird, reptile and frog translocations comprised 260 nodes, with 34/260 (13%) having two-way movements and 47/260 (18%) non-reciprocal movements. The median degree score (sum of in- and out-degree) was two (min 0, max 36) with a mean of 3.5 in a right skewed distribution. Most sites acted as receivers or senders of consignments with only a few having both high in- and high out-degree, and thus had characteristics that made them sites of interest for surveillance activities. These included the National Wildlife Centre at Mount Bruce, Tiritiri Matangi Island and Te Kakahu (Chalky Island). CONCLUSIONS: The presence of linking sites that join larger clusters within the network creates the potential for rapid disease spread if a pathogen were to be introduced. The important sites that supply or receive specimens for translocations are already well recognised by those performing translocations in New Zealand, and this paper provides further information by quantifying their role within the network.

Compatibility between livestock databases used for quantitative biosecurity response in New Zealand.

AIM: To characterise New Zealand's livestock biosecurity databases, and investigate their compatibility and capacity to provide a single integrated data source for quantitative outbreak analysis. METHODS: Contemporary snapshots of the data in three national livestock biosecurity databases, AgriBase, FarmsOnLine (FOL) and the National Animal Identification and Tracing Scheme (NAIT), were obtained on 16 September, 1 September and 30 April 2014, respectively, and loaded into a relational database. A frequency table of animal numbers per farm was calculated for the AgriBase and FOL datasets. A two dimensional kernel density estimate was calculated for farms reporting the presence of cattle, pigs, deer, and small ruminants in each database and the ratio of farm densities for AgriBase versus FOL calculated. The extent to which records in the three databases could be matched and linked was quantified, and the level of agreement amongst them for the presence of different species on properties assessed using Cohen's kappa statistic. RESULTS: AgriBase contained fewer records than FOL, but recorded animal numbers present on each farm, whereas FOL contained more records, but captured only presence/absence of animals. The ratio of farm densities in AgriBase relative to FOL for pigs and deer was reasonably homogeneous across New Zealand, with AgriBase having a farm density approximately 80% of FOL. For cattle and small ruminants, there was considerable heterogeneity, with AgriBase showing a density of cattle farms in the Central Otago region that was 20% of FOL, and a density of small ruminant farms in the central West Coast area that was twice that of FOL. Only 37% of records in FOL could be linked to AgriBase, but the level of agreement for the presence of different species between these databases was substantial (kappa>0.6). Both NAIT and FOL shared common farm identifiers which could be used to georeference animal movements, and there was a fair to substantial agreement (kappa 0.32-0.69) between these databases for the presence of cattle and deer on properties. CONCLUSIONS: The three databases broadly agreed with each other, but important differences existed in both species composition and spatial coverage which raises concern over their accuracy. Importantly, they cannot be reliably linked together to provide a single picture of New Zealand's livestock industry, limiting the ability to use advanced quantitative techniques to provide effective decision support during disease outbreaks. We recommend that a single integrated database be developed, with alignment of resources and legislation for its upkeep.

Serological markers of enterocyte damage and apoptosis in patients with celiac disease, autoimmune diabetes mellitus and diabetes mellitus type 2.

Impairment of mucosal barrier integrity of small intestine might be causative in immune-mediated gastrointestinal diseases. We tested the markers of epithelial apoptosis - cytokeratin 18 caspase-cleaved fragment (cCK-18), and enterocyte damage - intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14) in sera of patients with untreated celiac disease (CLD), those on gluten-free diet (CLD-GFD), patients with autoimmune diabetes mellitus (T1D), T1D with insulitis (T1D/INS), and diabetes mellitus type 2 (T2D). We found elevated levels of cCK-18 (P<0.001), I-FABP (P<0.01) and sCD14 (P<0.05) in CLD when compared to healthy controls. However, the levels of cCK-18 (P<0.01) and I-FABP (P<0.01) in CLD-GFD were higher when compared with controls. Interestingly, elevated levels of cCK-18 and I-FABP were found in T2D and T1D (P<0.001), and T1D/INS (P<0.01, P<0.001). Twenty-two out of 43 CLD patients were seropositive for cCK-18, 19/43 for I-FABP and 11/43 for sCD14; 9/30 of T2D patients were positive for cCK-18 and 5/20 of T1D/INS for sCD14, while in controls only 3/41 were positive for cCK-18, 3/41 for I-FABP and 1/41 for sCD14. We documented for the first time seropositivity for sCD14 in CLD and potential usefulness of serum cCK-18 and I-FABP as markers of gut damage in CLD, CLD-GFD, and diabetes.

Investigation of mortalities associated with Salmonella spp. infection in wildlife on Tiritiri Matangi Island in the Hauraki Gulf of New Zealand.

CASE HISTORY: Salmonellosis was suspected as the cause of death in eight wild animals on Tiritiri Matangi Island, in the Hauraki Gulf of New Zealand, between November and September 2011, including three hihi (Notiomystis cincta), a tuatara (Sphenodon punctatus), a masked lapwing (Vanellus miles novaehollandiae), and a saddleback (Philesturnus carunculatus). An outbreak investigation to identify the source and distribution of infection was undertaken over the summer of 2011-2012. CLINICAL AND LABORATORY FINDINGS: Surveillance of five species of forest bird (n=165) in December 2011 returned a single positive result for Salmonella spp. Environmental sampling of 35 key water sources and hihi supplementary feeding stations conducted in December 2011 and March 2012 returned isolates of S. enterica subspecies houtenae and S. enterica serovar Saintpaul from a stream, a dam and a supplementary feeding station. The same serotypes were identified in tissue samples collected from post mortem specimens of the affected birds, and their similarity was confirmed by pulsed-field gel electrophoresis. DIAGNOSIS: Mortality in wildlife associated with infection with S. enterica subspecies houtenae and S. enterica serovar Saintpaul. CLINICAL RELEVANCE: This is the first detection of these Salmonella spp. from wild birds in New Zealand. Our study highlights how active surveillance in response to observed disease emergence (here mortalities) can provide important insight for risk assessment and management within populations of endangered species and inform risk assessment in translocation planning.

Positivity for islet cell autoantibodies in patients with monogenic diabetes is associated with later diabetes onset and higher HbA1c level.

AIMS: Islet cell autoantibodies are associated with autoimmune insulitis and belong to the diagnostic criteria of type 1 diabetes mellitus. However, growing evidence suggests that autoantibodies are present in other types of diabetes. Here, we focus on the autoantibody incidence in Czech patients with maturity-onset diabetes of the young and analyse their functional relevance in terms of diabetes onset and control. METHODS: Autoantibodies against glutamic acid decarboxylase (GAD) 65 and protein tyrosine phosphatase islet antigen 2 (IA-2) were measured in a cohort of 28 Czech patients with maturity-onset diabetes of the young, all confirmed by genetic testing. Selected clinical data were correlated to the status and kinetics of autoantibodies. RESULTS: One quarter of patients with maturity-onset diabetes of the young examined (7/28; 25%) was positive for GAD or IA-2 autoantibodies. GAD autoantibodies were more prevalent (7/7) than IA-2 autoantibodies (1/7). The incidence of autoantibodies did not correlate with human leukocyte antigen status. The patients who were positive for the autoantibodies developed diabetes later than those who were autoantibody-negative, but had worse glycaemic control (increased HbA1c ). Expression of autoantibodies decreased with any improvement of diabetes compensation. Only one patient did not correspond to the above and displayed signs of combined signs of maturity-onset diabetes of the young and Type 1 diabetes. CONCLUSIONS: The data suggest transient but highly prevalent islet cell autoantibody expression in Czech patients with maturity-onset diabetes of the young. The autoantibodies were found in patients with delayed diabetes onset, and in times of insufficient diabetes control. As improvement of glycaemic control was associated with a decrease in levels of autoantibodies, their presence may reflect the kinetics of ß-cell destruction induced by causes other than autoimmune ones.

[Serious risk related to oral use of sodium phosphate solution]. / Závazná rizika spojená s uzíváním natrium-fosfátových projímadel.

Sodium phosphate solutions are commonly used to cleanse the bowel in preparation for colonoscopy, for barium enema or surgical procedures and eventually for treatment of severe constipation. Though relatively safe, these drugs must be used with caution in patients with kidney disease, small intestinal disorders, or poor gut motility and are prohibited in renal insufficiency and bowel obstruction. Especially elderly patients are at increased risk for phosphate intoxication due to decreased glomerular filtration rate, concomitant medication use, and systemic and gastrointestinal diseases. Sodium phosphate solution could induce by at-risk patients serious electrolyte abnormalities (hyperphosphatemia, hypocalcemia, hypokalemia) and acute kidney injury called acute phosphate nephropathy, which is potentially life-threatening condition with slowly progressive renal insufficiency. This article gives a report on two cases of severe adverse effects after administration of oral sodium phosphate solution: an elderly women who developed increase in serum phosphate with compensatory severe hypokalcemia with tetany; and an elderly man who developed acute phosphate nephropathy following colon preparation prior to colonoscopy and barium enema. Especially in elderly and in patients in whom sodium phosphate solution is contraindicated or should be used with caution, we recommend to use isosmotic macrogol (polyethylene glycol) solution for the bowel cleansing a for the treatment of constipation.

[Food intake regulation -  1st part]. / Regulace príjmu potravy -  I. cást.

The review article summarizes a very complex process of appetite regulation: the part focused on homeostatic regulation of food intake. The aim of homeostatic regulation is to achieve energy balance, stabile weight and optimal nutrient intake, in contrast to hedonic regulation of food intake, in which emotional and motivational factors are involved. Homeostatic regulation could be divided into shortterm and longterm regulation and comprises mainly gastrointestinal peptides, fat tissue hormones and central mechanisms localized in hypothalamus. It is a resultant of the action of orexigenic factors (increasing appetite and food intake) and anorexigenic factors (decreasing appetite and thus food intake), respectively. The anorexigenic factors include gastrointestinal peptides (e.g. cholecystokinin, glucagonlike peptide 1, bombesin, peptide YY and others), hormone of fat tissue leptin and centrally acting melanocortin system. On the contrary, orexigenic factors comprise of gastric ghrelin and centrally acting system of neuropeptide Y/ Agoutirelated peptide. Understanding the principles of the regulation of food intake is essential for comprehension of pathogenesis of eating disorders and obesity, whose prevalence has been recently increasing, and it provides potential targets for pharmacological interventions.

Higher insulin sensitivity in vegans is not associated with higher mitochondrial density.

BACKGROUND/OBJECTIVES: Vegans have a lower incidence of insulin resistance (IR)-associated diseases and a higher insulin sensitivity (IS) compared with omnivores. The aim of this study was to examine whether the higher IS in vegans relates to markers of mitochondrial biogenesis and to intramyocellular lipid (IMCL) content. SUBJECTS/METHODS: Eleven vegans and 10 matched (race, age, sex, body mass index, physical activity and energy intake) omnivorous controls were enrolled in a case-control study. Anthropometry, bioimpedance (BIA), ultrasound measurement of visceral and subcutaneous fat layer, parameters of glucose and lipid homeostasis, hyperinsulinemic euglycemic clamp and muscle biopsies were performed. Citrate synthase (CS) activity, mitochondrial DNA (mtDNA) and IMCL content were assessed in skeletal muscle samples. RESULTS: Both groups were comparable in anthropometric and BIA parameters, physical activity and protein-energy intake. Vegans had significantly higher glucose disposal (M-value, vegans 8.11±1.51 vs controls 6.31±1.57 mg/kg/min, 95% confidence interval: 0.402 to 3.212, P=0.014), slightly lower IMCL content (vegans 13.91 (7.8 to 44.0) vs controls 17.36 (12.4 to 78.5) mg/g of muscle, 95% confidence interval: -7.594 to 24.550, P=0.193) and slightly higher relative muscle mtDNA amount (vegans 1.36±0.31 vs controls 1.13±0.36, 95% confidence interval:-0.078 to 0.537, P=0.135). No significant differences were found in CS activity (vegans 18.43±5.05 vs controls 18.16±5.41 µmol/g/min, 95% confidence interval: -4.503 to 5.050, P=0.906). CONCLUSIONS: Vegans have a higher IS, but comparable mitochondrial density and IMCL content with omnivores. This suggests that a decrease in whole-body glucose disposal may precede muscle lipid accumulation and mitochondrial dysfunction in IR development.

[Metformin: the overlap of diabetology and oncology]. / Metformin: na pomezí diabetologie a onkologie.

Type 2 diabetes moderately increases predisposition for manifestation of tumor disease. Both drugs stimulating insulin secretion (insulin secretagogues) and insulin injection therapy also moderately increases risk of tumor manifestation (OR approx 1.3). According to some reports pyoglitazon therapy could be of increased risk of bladder cancer. On the other hand, hundreds of study on isolated cells, experimental animal models and retrospective studies in patients have shown preventive effect of metformin therapy on manifestation tumors of pancreas, breast, colorectum, liver, endometrium and ovary. More over, the prognosis of diabetic cancer patients on metformin therapy seems be better, than in diabetics without metformin treatment. These data are promising for future use of metformin for prevention and therapy of some malignant tumors.

[Effects of GLP-1 (glucagon-like peptide 1) on liver]. / Úcinky GLP-1 (glucagonlike peptide 1) na játra.

Effects of glucagonlike peptide 1 (GLP1) on liver cells are very intensively studied. In the metabolism of saccharides GLP1 stimulates synthesis of glycogen and reduces glucose production -  thus acting like insulin. In the lipid metabolism it enhances fatty acid oxidation and lipid transport from hepatocytes while reducing de novo lipogenesis -  effects more similar to glucagon action. Some studies suggest beneficial effects of GLP1 on oxidative stress, endoplasmic reticulum stress, production of inflammatory mediators and dysfunction of biliary secretion. Current results suggest that drugs affecting incretin system could be used in the treatment of certain liver diseases (e.g. NAFLD and NASH) in the future. In the following article we mention the known effects of GLP 1 on liver functions and liver metabolism and we point out its possible future therapeutic use in the treatment of liver diseases.