Evaluation of genotoxic effects of Apitol (cymiazole hydrochloride) in vitro by measurement of sister chromatid exchange

Apitol^®, with cymiazole hydrochloride as the active ingredient, is used in bee-keeping against the ectoparasitic mite Varroa destructor. The preparation was evaluated for genotoxicity in cultured human peripheral blood lymphocytes. Sister chromatid exchange, the mitotic index and the cell proliferation index were determined for three experimental concentrations of Apitol^® (0.001, 0.01 and 0.1 mg/ml). All concentrations significantly (p < 0.001) increased the mitotic index (MI = 7.35 ± 0.18%, 8.31 ± 0.20% and 12.33 ± 0.25%, respectively), the proliferative index (PI = 1.83 ± 0.01, 1.84 ± 0.01 and 1.88 ± 0.02, respectively) and the frequency of sister chromatid exchange (SCE = 8.19 ± 1.81, 8.78 ± 1.80 and 13.46 ± 1.88, respectively), suggesting that cymiazole hydrochloride has genotoxic potential.     

Glucagon-like peptide-1 protects mesenteric endothelium from injury during inflammation

Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived hormone with cellular protective actions. We hypothesized that GLP-1 would protect the endothelium from injury during inflammation. Our aims were to determine the: (1) effect of GLP-1 on basal microvascular permeability, (2) effect of GLP-1 on increased microvascular permeability induced by lipopolysaccaride (LPS), (3) involvement of the GLP-1 receptor in GLP-1 activity, and (4) involvement of the cAMP/PKA pathway in GLP-1 activity. Microvascular permeability (L_p) of rat mesenteric post-capillary venules was measured in vivo. First, the effect of GLP-1 on basal L_p was measured. Second, after systemic LPS injection, L_p was measured after subsequent perfusion with GLP-1. Thirdly, L_p was measured after LPS injection and perfusion with GLP-1 + GLP-1 receptor antagonist. Lastly, L_p was measured after LPS injection and perfusion with GLP-1 + inhibitors of the cAMP/PKA pathway. Results are presented as mean area under the curve (AUC) ± SEM. GLP-1 had no effect on L_p (AUC: baseline = 27 ± 1.4, GLP-1 = 1 ± 0.4, p = 0.08). LPS increased L_p two-fold (AUC: LPS = 54 ± 1.7, p < 0.0001). GLP-1 reduced the LPS increase in L_p by 75% (AUC: LPS + GLP-1 = 34 ± 1.5, p < 0.0001). GLP-1 antagonism reduced the effects of GLP-1 by 60% (AUC: LPS + GLP-1 + antagonist = 46 ± 2.0, p < 0.001). The cAMP synthesis inhibitor reduced the effects of GLP-1 by 60% (AUC: LPS + GLP-1 + cAMP inhibitor = 46 ± 1.5, p < 0.0001). The PKA inhibitor reduced the effects of GLP-1 by 100% (AUC: LPS + GLP-1 + PKA inhibitor = 56 ± 1.5, p < 0.0001). GLP-1 attenuates the increase in microvascular permeability induced by LPS. GLP-1 may protect the endothelium during inflammation, thus decreasing third-space fluid loss.     

The effect of exenatide re-exposure on safety and efficacy

Exenatide, a synthetic peptide originally isolated from salivary secretions of Heloderma suspectum, like other subcutaneously injected peptides, can cause antibody formation. Despite that antibody formation has been observed in some patients, results from previous clinical trials have not shown safety and efficacy concerns in exenatide-naïve patients. The objective of this multicenter, open-label study was to investigate the response of anti-exenatide antibody formation and the incidence of immune-related and hypersensitivity reactions after exenatide re-exposure. Fifty-eight patients (57% male; 59 ± 10 years; weight 85 ± 19 kg; HbA1c 8.1 ± 0.9%; duration of diabetes 10 ± 5 years) were enrolled. At study initiation, 98.3% of patients were taking 1 or more antidiabetes drugs, including oral medication and various types of insulin. Treatment-emergent adverse events (TEAEs) at any time during the study were observed in 40 and 47% of patients with positive and negative treatment-emergent antibodies, respectively. Immune-related AEs were observed in 6 patients (4 were antibody positive). These AEs had not been reported in their previous exposure to exenatide. Re-exposure to exenatide did not result in increased hypersensitivity reactions. Overall, 72% of patients had a baseline to endpoint reduction in HbA1c (range −0.1 to −2.8%), and 87% of antibody negative versus 62% of antibody positive patients had an HbA1c endpoint reduction. The study design and the patients’ baseline characteristics, including diabetes treatment at study initiation, are confounding factors limiting clinical conclusions on exenatide's glycemic effect in this patient population. The study results indicate that anti-exenatide antibody formation did not increase the incidence of TEAEs in patients re-exposed to exenatide.     

Growth and protein synthesis of barramundi, Lates calcarifer, fed lupin as a partial protein replacement

Protein synthesis is an essential growth process in all animals. Little information is available on post-prandial protein synthesis and even less where different protein sources are compared. Protein synthesis was measured at 4 and 24 h after feeding juvenile barramundi in order to determine the effect of using lupin as a partial protein replacement for fish meal on the post-prandial protein metabolism. Juvenile barramundi (4.3 ±0.6 g) were held in a recirculation system (27 °C, salinity 10‰ and 24 h light) for 15 days. Fish were fed one of two isonitrogenous isoenergetic diets (40% crude protein, 16% lipid and 18.5 GE MJ kg^− 1). One diet was formulated with 100% fish meal as the protein source while the other had 45% of the protein replaced with lupin ingredients (lupin kernel meal (Lupinus angustifolius) and lupin protein concentrate). All fish were fed a ration of 6%·d^− 1 and feed intake was not significantly different between the two diets. Specific growth rate (SGR) and growth efficiency (in relation to protein (PPV) and energy (PEV)) were 6.5 ± 0.14%·d^− 1, 43.8 ± 2.72% and 38.31 ± 1.56%, respectively, and were not significantly different between the two diets. There was no significant difference in protein synthesis between the two diets at 4 and 24 h after feeding, however protein synthesis was significantly higher 4 h after feeding than at 24 h (p = 0.02). Neither growth performance nor protein metabolism was altered by replacing 45% of the protein with lupin protein and indicated this to be a suitable protein source for barramundi feeds.     

Efficacy of three commercially available ballast water biocides against vegetative microalgae, dinoflagellate cysts and bacteria

One proposed solution to the problem of ballast-mediated aquatic invasions involves chemically treating ballast water to kill key target organisms. Here, we examine the efficacy of three commercially available ballast water biocides using vegetative microalgae, dinoflagellate resting cysts and bacteria as test organisms. Chemicals tested were the ballast water biocides SeaKleen^® and Peraclean^® Ocean, and the chlorine dioxide biocide Vibrex^®. Results demonstrate that the applicability of each of the three chemical biocides as a routine ballast water treatment is limited by factors such as cost, biological effectiveness and possible residual toxicity of the discharged ballast water (assessed on the basis of impact on motility of vegetative marine microalgae). Of the three biocides tested, Peraclean^® Ocean appears to hold the most potential; however its effectiveness in shipboard trials is yet to be proven. Peraclean^® Ocean was biodegradable within 2–6 weeks (initial concentration of 200 ppm), could effectively inactivate resting cysts of the marine dinoflagellates Gymnodinium catenatum, Alexandrium catenella and Protoceratium reticulatum at 400 ppm, could control bacterial growth of Escherichia coli, Staphylococcus aureus, Listeria innocua and Vibrio alginolyticus at 125–250 ppm, and could eliminate vegetative dinoflagellate cells at a concentration of 100 ppm. SeaKleen^® eliminated vegetative microalgae at 2 ppm and could control resting cysts of the dinoflagellates G. catenatum and P. reticulatum at a concentration of 6 and 10 ppm, respectively, when exposed for a period of 2 weeks. SeaKleen^® did not inactivate resting cysts of A. catenella at a concentration of 10 ppm and was found to degrade at a rate that could result in the discharge of residual toxic water into the marine environment. Together with the poor bactericidal properties of SeaKleen^® (100–200 ppm required), this may limit the use of this biocide as a routine treatment option. Vibrex^® is not a suitable ballast water treatment option due to the need for hydrochloric acid as an activator, however it was found to be the most effective against bacteria (complete inhibition at 15 ppm) indicating that onboard chlorine dioxide generators may provide an effective bacterial treatment option. The performance of these biocides was adversely influenced by a variety of factors including low water temperatures (6 °C compared to 17 °C), light versus dark conditions, and the presence of humus-rich seawater and ballast water sediments.     

In vitro biohydrogenation of four dietary fats

This study was designed to determine in vitro rates of biohydrogenation of dietary unsaturated fatty acids by a mixed population of rumen microbes. The four dietary fats [Alifet High-Energy^® (AHE), Alifet-Repro^® (AR), Megalac^® (MG), and Energy Booster^® (EB)] differ in method of preparation, fatty acid composition, or both of these factors. Dietary fats (20 mg) were incubated with 4 mL strained rumen fluid diluted with 16 mL of medium, 0.8 mL of reducing solution buffer, and 200 mg of a synthetic diet (370 g cellulose, 370 g starch, and 160 g casein per kg DM) at 37 °C. Total contents were collected after 0, 6, 12, 24, or 36 h and change in fatty acid content determined. Disappearance of oleic acid was minimal (0.05–0.20) in AR and MG but moderate (about 0.60) in AHE and EB after 36 h of incubation. Rate of biohydrogenation of linoleic and linolenic acids from AR were similar (0.025 ± 0.009 h⁻¹) and 0.65 of these fatty acids remained intact after 36 h. Rate of biohydrogenation of linoleic acid was four times greater than for oleic acid (0.040 ± 0.013 h⁻¹ versus 0.009 ± 0.002 h⁻¹) in MG. Thus, 0.65 of the linoleic acid but only 0.20 of the oleic acid had disappeared from MG after 36 h. Trans-11 and trans-12 were the predominant trans-isomers in AHE and AR cultures whereas trans-9 and trans-10 were the predominant trans-isomers in EB and MG cultures. None of the dietary fats contained conjugated linoleic acid (CLA) but CLA was present in the incubation inoculum. The amount of CLA decreased with time but this was not affected by source of dietary fat. Most (0.90–0.95) of the long-chain fatty acids eicosapentaenoic (EPA) and docosahexaenoic (DHA) in AR remained after 36 h of incubation. Results demonstrate that biohydrogenation varied among fatty acids and among source of dietary fat and indicate that AR can be used to increase post-ruminal supply of linolenic, EPA and DHA.     

Benefits to host sea anemones from ammonia contributions of resident anemonefish

Large ectosymbionts (especially fishes and crustaceans) may have major impacts on the physiology of host cnidarians (sea anemones and corals), but these effects have not been well quantified. Here we describe impacts on giant sea anemone hosts (Entacmaea quadricolor) and their endosymbiotic zooxanthellae (Symbiodinium spp.) from the excretion products of anemonefish guests (Amphiprion bicinctus) under laboratory conditions. Starved host anemones were maintained with anemonefish, ammonia supplements (= NH₃ gas and NH₄⁺ ion), or neither for 2 mo. In the presence of external ammonia supplements or resident anemonefish, the zooxanthellae within host anemones increased in abundance (173% and 139% respectively), and provided the hosts with energy that minimized host body size loss. In contrast, anemones cultured with neither ammonia nor anemonefish harbored significantly lower abundances of zooxanthellae (84% of initial abundance) and decreased > 60% in body size. Although they maintained higher zooxanthella abundances, anemones cultured with either ammonia supplements or resident anemonefish exhibited significantly lower ammonia uptake rates (0.065 ± 0.005 µmol g^- 1 h^- 1, and 0.052 ± 0.018 µmol g^- 1 h^- 1 respectively) than did control anemones (0.119 ± 0.009 µmol g^- 1 h^- 1), indicating that their zooxanthellae were more nitrogen sufficient. We conclude that, in this multi-level mutualism, ammonia supplements provide essentially the same level of physiological contribution to host anemones and zooxanthellae as do live resident fish. This nutrient supplement reduces the dependence of the zooxanthellae on host feeding, and allows them to provide abundant photosynthetically-produced energy to the host.     

Insecticidal effect of Beauveria bassiana (Balsamo) Vuillemin (Ascomycota: Hypocreaes) in combination with three diatomaceous earth formulations against Sitophilus granarius (L.) (Coleoptera: Curculionidae)

The insecticidal effect of the entomopathogenic fungus Beauveria bassiana (Balsamo) Vuillemin (Ascomycota: Hypocreaes) in combination with three diatomaceous earth (DE) formulations against adults of the granary weevil, Sitophilus granarius (L.) (Coleoptera: Curculionidae) was tested in the laboratory. The three DEs were Insecto™, SilicoSec^® and PyriSec^®. The fungus was applied at 400 ppm alone, or in combination with 200 ppm of each of the three DEs. Mortality was measured after 7 d of exposure. Bioassays were conducted at three temperatures 20, 25 and 30 °C and two relative humidities (rh) 55% and 75%. On wheat treated with B. bassiana alone, mortality was higher at 55% than at 75% rh. Also, the fungus alone was less effective at 20 °C than at the other two temperatures tested, but mortality did not exceed 52% for any of the conditions tested. Similar mortality levels were also noted on wheat treated with each of the three DEs alone. The simultaneous presence of B. bassiana and DE increased weevil mortality. In this combination, mortality was higher at high temperatures and low rh, and this effect was similar for all DEs tested. Progeny production on wheat treated with B. bassiana was higher that the respective progeny counts in the DE-treated wheat. The results indicate that a combination of B. bassiana and DEs is effective against S. granarius, under a broad range of temperature and rh levels in stored wheat.     

Seasonal variation in thermal energetics of the Australian owlet-nightjar (Aegotheles cristatus)

Many birds living in regions with seasonal fluctuations in ambient temperatures (T_a) typically respond to cold by increasing insulation and adjusting metabolic rate. Seasonal variation in thermal physiology has not been studied for the Caprimulgiformes, an order of birds that generally have basal metabolic rates (BMR) lower than predicted for their body mass. We measured the metabolic rate and thermal conductance of Australian owlet-nightjars (Aegotheles cristatus) during summer and winter using open-flow respirometry. Within the thermoneutral zone (TNZ; 31.3 to 34.8 °C), there was no seasonal difference in BMR or thermal conductance (C), but body temperature was higher in summer- (38.2 ± 0.3 °C) than winter-acclimatized (37.1 ± 0.5 °C) birds. Below the TNZ, resting metabolic rate (RMR) increased linearly with decreasing T_a, and RMR and C were higher for summer- than winter-acclimatized birds. The mean mass-specific BMR of owlet-nightjars (1.27 mL O₂ g^− 1 h^− 1) was close to the allometrically predicted value for a 45 g Caprimulgiformes, but well below that predicted for birds overall. These results suggest that owlet-nightjars increase plumage insulation to cope with low winter T_a, which is reflected in the seasonal difference in RMR and C below the TNZ, rather than adjusting BMR.     

Clean conversion of cellulose into fermentable glucose

We studied the process of conversion of microcrystalline-cellulose into fermentable glucose in the formic acid reaction system using cross polarization/magic angle spinning ¹³C-nuclear magnetic resonance, X-ray diffraction and Fourier transform infrared spectroscopy. The results indicated that formic acid as an active agent was able to effectively penetrate into the interior space of the cellulose molecules, thus collapsing the rigid crystalline structure and allowing hydrolysis to occur easily in the amorphous zone as well as in the crystalline zone. The microcrystalline-cellulose was hydrolyzed using formic acid and 4% hydrochloric acid under mild conditions. The effects of hydrochloric acid concentration, the ratio of solid to liquid, temperature (55–75 °C) and retention time (0–9 h), and the concentration of glucose were analyzed. The hydrolysis velocities of microcrystalline-cellulose were 6.14 × 10^− 3 h^− 1 at 55 °C, 2.94 × 10^− 2 h^− 1 at 65 °C, and 6.84 × 10^− 2 h^− 1 at 75 °C. The degradation velocities of glucose were 0.01 h^− 1 at 55 °C, 0.14 h^− 1 at 65 °C, 0.34 h^− 1 at 75 °C. The activation energy of microcrystalline-cellulose hydrolysis was 105.61 kJ/mol, and the activation energy of glucose degradation was 131.37 kJ/mol.     

Enhancing antimicrobial properties of dyed and finished cotton fabrics

1,2,3-Benzothiazole-7-thiocarboxylic acid-S-methylester (commercially known as Actigard^® AM-87) was utilized to impart cotton fabric durable antimicrobial properties. Finishing treatment was carried out under a variety of conditions. The latter were included, effect of pH, concentration of antibacterial agents, curing temperature and curing time. The effect of fabric construction, mercerization, and dyeing with different dyestuff were also investigated. The study was also extended to investigate the technical feasibility of combining antimicrobial finishing treatment in question with other finishing treatment generally carried out on cotton fabric, like soft finishing and crease recovery finishing. The treated fabrics were monitored for antimicrobial properties before and after washing. The treated fabrics were also evaluated for the physio-mechanical properties like fabric tensile strength, elongation at break (or bursting strength for knitted fabric), wettability, crease recovery angle, whiteness index and roughness. Results obtained show that, the most appropriate conditions for treatment cotton fabric with Actigard^® are: padding the cotton fabric in aqueous solution containing 6% Actigard^® at pH 5 (adjusted using formic acid) then squeezed to wet pick up of 100%, dried at 80 °C for 5 min then cured at 100 °C for 150 s. The untreated cotton fabric did not show any antimicrobial activity towards Staphylococcus aureus or Escherichia coli. Treatment of cotton fabric with Actigard^® improves its antimicrobial properties towards S. aureus or E. coli. It is also observed that, treatment of cotton fabric with Actigard^® marginally decreases fabric tensile strength, elongation at break, roughness and WI, whereas; both wettability and crease recovery angle remain practically intact. This was observed whether the fabric was pre-mercerized or not.     

Neuronal membrane potential is mildly depolarized in the anoxic turtle cortex

Neuronal membrane potential (E_m) regulates the activity of excitatory voltage-sensitive channels. Anoxic insults lead to a severe loss of E_m and excitotoxic cell death (ECD) in mammalian neurons. Conversely, anoxia-tolerant freshwater turtle neurons depress energy usage during anoxia by altering ionic conductance to reduce neuronal excitability and ECD is avoided. This wholesale alteration of ion channel and pump activity likely has a significant effect on E_m. Using the whole-cell patch clamp technique we recorded changes in E_m from turtle cortical neurons during a normoxic to anoxic transition in the presence of various ion channel/pump modulators. E_m did not change with normoxic perfusion but underwent a reversible, mild depolarization of 8.1 ± 0.2 mV following anoxic perfusion. This mild anoxic depolarization (MAD) was not prevented by the manipulation of any single ionic conductance, but was partially reduced by pre-treatment with antagonists of GABA_A receptors (5.7 ± 0.5 mV), cellular bicarbonate production (5.3 ± 0.2 mV) or K⁺ channels (6.0 ± 0.2 mV), or by perfusion of reactive oxygen species scavengers (5.2 ± 0.3 mV). Furthermore, all of these treatments induced depolarization in normoxic neurons. Together these data suggest that the MAD may be due to the summation of numerous altered ion conductance states during anoxia.     

The routine metabolic rate of mulloway (Argyrosomus japonicus: Sciaenidae) and yellowtail kingfish (Seriola lalandi: Carangidae) acclimated to six different temperatures

This study compared the mass-specific routine metabolic rate (RMR) of similar sized mulloway (Argyrosomus japonicus), a sedentary species, and yellowtail kingfish (Seriola lalandi), a highly active species, acclimated at one of several temperatures ranging from 10–35 °C. Respirometry was carried out in an open-top static system and RMR corrected for seawater–atmosphere O₂ exchange using mass-balance equations. For both species RMR increased linearly with increasing temperature (T). RMR for mulloway was 5.78T − 29.0 mg O₂ kg^− 0.8 h^− 1 and for yellowtail kingfish was 12.11T − 39.40 mg O₂ kg^− 0.8 h^− 1. The factorial difference in RMR between mulloway and yellowtail kingfish ranged from 2.8 to 2.2 depending on temperature. The energetic cost of routine activity can be described as a function of temperature for mulloway as 1.93T − 9.68 kJ kg^− 0.8 day^− 1 and for yellowtail kingfish as 4.04T − 13.14 kJ kg^− 0.8 day^− 1. Over the full range of temperatures tested Q₁₀ values were approximately 2 for both species while Q₁₀ responses at each temperature increment varied considerably with mulloway and yellowtail kingfish displaying thermosensitivities indicative of each species respective niche habitat. RMR for mulloway was least thermally dependent at 28.5 °C and for yellowtail kingfish at 22.8 °C. Activation energies (E_a) calculated from Arrhenius plots were not significantly different between mulloway (47.6 kJ mol^− 1) and yellowtail kingfish (44.1 kJ mol^− 1).     

Partial characterization of a malonyl-CoA-sensitive carnitine O-palmitoyltransferase I from Macrobrachium borellii (Crustacea: Palaemonidae)

The shuttle system that mediates the transport of fatty acids across the mitochondrial membrane in invertebrates has received little attention. Carnitine O-palmitoyltransferase I (EC 2.3.1.21; CPT I) is a key component of this system that in vertebrates controls long-chain fatty acid β-oxidation. To gain knowledge on the acyltransferases in aquatic arthropods, physical, kinetic, regulatory and immunological properties of CPT of the midgut gland mitochondria of Macrobrachium borellii were assayed. CPT I optimum conditions were 34 °C and pH = 8.0. Kinetic analysis revealed a Km for carnitine of 2180 ± 281 μM and a Km for palmitoyl-CoA of 98.9 ± 8.9 μM, while V_max were 56.5 ± 6.6 and 36.7 ± 4.8 nmol min^− 1 mg protein^− 1, respectively. A Hill coefficient, n ~ 1, indicate a Michaelis–Menten behavior. The CPT I activity was sensitive to regulation by malonyl-CoA, with an IC₅₀ of 25.2 μM. Electrophoretic and immunological analyses showed that a 66 kDa protein with an isoelectric point of 5.1 cross-reacted with both rat liver and muscle-liver anti CPT I polyclonal antibodies, suggesting antigenic similarity with the rat enzymes. Although CPT I displayed kinetic differences with insect and vertebrates, prawn showed a high capacity for energy generation through β-oxidation of long-chain fatty acids.     

Safety and Efficacy of Exenatide in Combination with Insulin in Patients with Type 2 Diabetes Mellitus

ObjectiveTo evaluate the 1-year efficacy and safety of treatment with exenatide in combination with insulin (a use not approved by the US Food and Drug Administration).MethodsElectronic medical records of 3 private-practice endocrinologists were reviewed to identify patients with type 2 diabetes mellitus (T2DM) receiving insulin who subsequently began exenatide therapy. Patients’ baseline hemoglobin A1c (A1C) levels, weights, lipid profiles, blood pressures, and medication utilization were compared with corresponding data obtained after a minimal duration of 12 months.ResultsWe identified 134 patients with T2DM initiating exenatide therapy in combination with insulin between April 2005 and April 2006. One-year follow-up information was available for 124 patients. Exenatide use resulted in a significant 0.87% reduction in A1C (P < .001), despite a 45% discontinuation of premeal insulin use (P < .001), a 9-U reduction in mean premeal insulin doses (P = .0066), a reduction in the median number of daily insulin injections from 2 to 1 (P = .0053), and a 59% discontinuation rate of sulfonylurea use (P = .0088). Exenatide use was associated with a mean weight loss of 5.2 kg (P < .001), with 72% of evaluable patients losing weight. Forty-eight patients (36%) discontinued exenatide therapy during the first year, primarily attributable to gastrointestinal intolerance. Fourteen patients (10%) experienced hypoglycemia, most of which was mild.ConclusionExenatide in combination with insulin in patients with T2DM was associated with significant reductions in A1C and weight after 1 year of therapy. This was offset, however, by an exenatide discontinuation rate of 36%, primarily due to adverse gastrointestinal effects. (Endocr Pract. 2008;14:285-292)     

Glucagon-like peptide analogues for type 2 diabetes mellitus: systematic review and meta-analysis

Background

Glucagon-like peptide (GLP-1) analogues are a new class of drugs used in the treatment of type 2 diabetes. They are given by injection, and regulate glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, suppressing glucagon secretion, and delaying gastric emptying and promoting satiety. This systematic review aims to provide evidence on the clinical effectiveness of the GLP-1 agonists in patients not achieving satisfactory glycaemic control with one or more oral glucose lowering drugs.

Methods

MEDLINE, EMBASE, the Cochrane Library and Web of Science were searched to find the relevant papers. We identified 28 randomised controlled trials comparing GLP-1 analogues with placebo, other glucose-lowering agents, or another GLP-1 analogue, in patients with type 2 diabetes with inadequate control on a single oral agent, or on dual therapy. Primary outcomes included HbA1c, weight change and adverse events.

Results

Studies were mostly of short duration, usually 26 weeks. All GLP-1 agonists reduced HbA1c by about 1% compared to placebo. Exenatide twice daily and insulin gave similar reductions in HbA1c, but exenatide 2 mg once weekly and liraglutide 1.8 mg daily reduced it by 0.20% and 0.30% respectively more than glargine. Liraglutide 1.2 mg daily reduced HbA1c by 0.34% more than sitagliptin 100 mg daily. Exenatide and liraglutide gave similar improvements in HbA1c to sulphonylureas. Exenatide 2 mg weekly and liraglutide 1.8 mg daily reduced HbA1c by more than exenatide 10 μg twice daily and sitagliptin 100 mg daily. Exenatide 2 mg weekly reduced HbA1c by 0.3% more than pioglitazone 45 mg daily. Exenatide and liraglutide resulted in greater weight loss (from 2.3 to 5.5 kg) than active comparators. This was not due simply to nausea. Hypoglycaemia was uncommon, except when combined with a sulphonylurea. The commonest adverse events with all GLP-1 agonists were initial nausea and vomiting. The GLP-1 agonists have some effect on beta-cell function, but this is not sustained after the drug is stopped.

Conclusions

GLP-1 agonists are effective in improving glycaemic control and promoting weight loss.     

Net release of dissolved organic matter by the scleractinian coral Acropora pulchra

The net production of dissolved organic matter (DOM) and dissolved combined and free amino acids (DCAA and DFAA, respectively) by the hermatypic coral Acropora pulchra was measured in the submerged condition, and the production rates were normalized to the coral surface area, tissue biomass, and net photosynthetic rates by zooxanthellae. When normalized to the unit surface area, the production rates of dissolved organic carbon and nitrogen (DOC and DON, respectively) were 37 and 4.4 nmol cm^− 2 h^− 1, respectively. Comparing with the photosynthetic rate by zooxanthellae, which was measured by ¹³C-tracer accumulation in the soft tissue of the coral colony, the release rate of DOC corresponded to 5.4% of the daily net photosynthetic production. The tissue biomass of the coral colony was 178 µmol C cm^− 2 and 23 µmol N cm^− 2, indicating that the release of DOC and DON accounted for 0.021% h^− 1 and 0.019% h^− 1 of the tissue C and N, respectively. The C:N ratios of the released DOM (average 8.4) were not significantly different from those of the soft tissue of the coral colonies (average 7.7). While DFAA did almost not accumulate in the incubated seawater, DCAA was considerably released by the coral colonies at the rate of 2.1 nmol cm^− 2 h^− 1 on average. Calculating C and N contents of the hydrolyzable DCAA, it was revealed that about 20% and 50%–60% of the released bulk DOC and DON, respectively, were composed of DCAA.     

Protocols for hyperlactatemia induction in the lactate minimum test adapted to swimming rats

The lactate minimum test (LACmin) has been considered an important indicator of endurance exercise capacity and a single session protocol can predict the maximal steady state lactate (MLSS). The objective of this study was to determine the best swimming protocol to induce hyperlactatemia in order to assure the LACmin in rats (Rattus norvegicus), standardized to four different protocols (P) of lactate elevation. The protocols were P1: 6 min of intermittent jumping exercise in water (load of 50% of the body weight — bw); P2: two 13% bw load swimming bouts until exhaustion (tlim); P3: one tlim 13% bw load swimming bout; and P4: two 13% bw load swimming bouts (1st 30 s, 2nd to tlim), separated by a 30 s interval. The incremental phase of LACmin beginning with initial loads of 4% bw, increased in 0.5% at each 5 min. Peak lactate concentration was collected after 5, 7 and 9 min (mmol L^− 1) and differed among the protocols P1 (15.2 ± 0.4, 14.9 ± 0.7, 14.8 ± 0.6) and P2 (14.0 ± 0.4, 14.9 ± 0.4, 15.5 ± 0.5) compared to P3 (5.1 ± 0.1, 5.6 ± 0.3, 5.6 ± 0.3) and P4 (4.7 ± 0.2, 6.8 ± 0.2, 7.1 ± 0.2). The LACmin determination success rates were 58%, 55%, 80% and 91% in P1, P2, P3 and P4 protocols, respectively. The MLSS did not differ from LACmin in any protocol. The LACmin obtained from P4 protocol showed better assurance for the MLSS identification in most of the tested rats.     

Diet and physiological responses of Spondyliosoma cantharus (Linnaeus, 1758) to the Caulerpa racemosa var. cylindracea invasion

Marine invasions are a worldwide problem that involves changes in communities and the acclimation of organisms to them. The invasive Chlorophyte Caulerpa racemosa var. cylindracea is widespread in the Mediterranean and colonises large areas from 0 to 70 m in depth. The omnivorous fish Spondyliosoma cantharus presents a high frequency of occurrence of C. racemosa in the stomach contents at invaded areas (76.3%) while no presence of C. racemosa was detected in control areas. The isotopic composition of muscle differed significantly between invaded and non-invaded sites for δ¹³C (− 16.67‰ ± 0.09 and − 17.67‰ ± 0.08, respectively), δ¹⁵N (10.22‰ ± 0.22 and 9.32‰ ± 0.18, respectively) and the C:N ratio (2.01 ± 0.0002 and 1.96 ± 0.009, respectively). Despite the high frequency of occurrence of C. racemosa in the stomach contents of S. cantharus and its important contribution to the δ¹³C source (20.7% ± 16.2), the contribution of C. racemosa to the δ¹⁵N in S. cantharus food sources was very low (6.6% ± 5.8). Other invertebrate prey such as decapods and polychaetes were more important contributors to the δ¹⁵N source at both invaded and non-invaded sites. Activation of enzymatic pathways (catalase, superoxide dismutase, glutathione-s-tranferase, 7-ethoxy resorufin O-de-ethylase) but not a significant increase in lipid peroxidation MDA (0.49 ± 0.01 nmol/mg prot at non-invaded and 0.53 ± 0.01 nmol/mg prot at invaded sites) was observed in S. cantharus individuals living in C. racemosa-invaded sites compared with control specimens. The low δ¹⁵N contribution values of C. racemosa by S. cantharus together with the toxicity demonstrated by the activation of the antioxidant defences and the important contribution of invertebrate prey to the δ¹⁵N could mean that the ingestion of C. racemosa by S. cantharus might be unintentional during the predation of invertebrate preys living underneath the entanglement of the C. racemosa fronds and stolons mats.     

Effect of renoguanylin on hydrogen/bicarbonate ion transport in rat renal tubules

Renoguanylin (REN) is a recently described member of the guanylin family, which was first isolated from eels and is expressed in intestinal and specially kidney tissues. In the present work we evaluate the effects of REN on the mechanisms of hydrogen transport in rat renal tubules by the stationary microperfusion method. We evaluated the effect of 1 μM and 10 μM of renoguanylin (REN) on the reabsorption of bicarbonate in proximal and distal segments and found that there was a significant reduction in bicarbonate reabsorption. In proximal segments, REN promoted a significant effect at both 1 and 10 μM concentrations. Comparing control and REN concentration of 1 μM, JHCO₃⁻, nmol cm^− 2 s^− 1 − 1,76 ± 0,11_control × 1,29 ± 0,08_{REN 10 μM}; P < 0.05, was obtained. In distal segments the effect of both concentrations of REN was also effective, being significant e.g. at a concentration of 1 μM (JHCO₃⁻, nmol cm^− 2 s⁻ 1 − 0.80 ± 0.07_control × 0.60 ± 0.06_{REN 1 μM}; P < 0.05), although at a lower level than in the proximal tubule. Our results suggest that the action of REN on hydrogen transport involves the inhibition of Na⁺/H⁺exchanger and H⁺-ATPase in the luminal membrane of the perfused tubules by a PKG dependent pathway.