Morphology and phylogeny of Henneguya jocu n. sp. (Myxosporea,Myxobolidae), infecting the gills of the marine fish Lutjanus jocu

Henneguya jocu n. sp. (Myxosporea, Myxobolidae) is described from the gill lamellae of the marine teleost fish Lutjanus jocu, with a focus on ultrastructural and molecular features. This myxosporean forms subspherical cysts up to ∼260 μm × 130 μm long, and develops asynchronously. Mature myxospores ellipsoidal with a bifurcated caudal process. Myxospore length 10.9 ± 0.4 μm (n = 50); width, 8.2 ± 0.3 μm (n = 50); and thickness, 2.9 ± 0.5 μm (n = 50). Two equal caudal processes, 34.1 ± 1.0 μm long (n = 50); and total myxospore length, 45.2 ± 1.0 μm (n = 50). Two symmetric valves surround two ellipsoidal polar capsules, 5.0 ± 0.3 × 1.4 ± 0.2 μm (n = 20), each containing an isofilar polar filament forming 4–5 coils along the inner wall of these structures, as well as a binucleated sporoplasm presenting a spherical vacuole and several globular sporoplasmosomes. Both the morphological data and molecular analysis of the SSU rDNA gene identify this parasite as a new species of the genus Henneguya. Maximum Likelihood and Maximum Parsimony analyses further indicate that the parasite clusters within others marine Myxobolidae species, forming a group alongside other Henneguya species described from marine hosts.     

Morphological and molecular characterization of Thelohanellus macrovacuolaris n. sp. (Myxosporea: Bivalvulida) infecting the palate in the mouth of common carp Cyprinus carpio L. in China

Thelohanellus macrovacuolaris n. sp. is described during a survey on myxozoan diversity of common carp Cyprinus carpio L. in China. It is characterized by the presence of round or ellipsoidal plasmodium in the palate in the mouth of host. Mature spores were pyriform in frontal view, lemon shaped in lateral view, measuring 21.6 ± 0.9 (19.3–23.8) long, 12.5 ± 0.7 (10.3–13.6) wide, and 10.2 ± 0.4 (9.8–11.8) thick. Most spores were surrounded by the membrane sheath. Single polar capsule was round with an apophysis at its top end presented close to apex of spore, measuring 9.1 ± 0.6 (8.0–10.0) in length, 8.6 ± 0.5 (7.8–9.6) in width. Polar filaments coiled, with 7 to 8 turns. A large, round iodinophilous vacuole was present, with 5.8–7.5 in diameter. The present species is morphologically distinct from all other Thelohanellus species. The BLAST search indicated that the newly obtained small subunit ribosomal RNA (ssrRNA) gene sequence of T. macrovacuolaris n. sp. did not match any available sequences in GenBank. Phylogenetically, T. macrovacuolaris n. sp. was placed sister to Thelohanellus wangi in the Thelohanellus clade. Both morphology and ssrRNA gene sequence data revealed that the present parasite is a new species of genus Thelohanellus.     

Supplementary studies and molecular data on Henneguya cerebralis Pronin, 1972 (Myxozoa: Myxosporea), a parasite from Kosogol grayling Thymallus arcticus nigrescens in Mongolia

Henneguya cerebralis Pronin, 1972 (Myxozoa) was described from Kosogol graylings Thymallus arcticus nigrescens Dorogostaisky, 1923 in Lake Khovsgol (Mongolia) in 1972.H. cerebralis was redescribed using critical morphological features and 18S ribosomal DNA (rDNA) gene sequence. Parasite infects cranial cartilage of fish host. Plasmodia are white rounded or ovoid, by 0.1 to 2 mm in size, containing large quantities of spores. Spore body is ovoid or rounded, 11.18 ± 0.13 μm (range 9,71–12,56) in length and 9.06 ± 0.16 μm (range 7.22–10,06) in width with equal polar capsules (4.7 × 2.6 μm). The two caudal appendages have different lengths (one of them was shorter in 20%).Phylogenetic position inferred by 18S rDNA shows that H. cerebralis is closely related with H. zschokkei, H. nuesslini, H. salminicola and H. cartilaginis which are histozoic parasites of salmonid fish.     

Ultrastructure and phylogeny of Glugea arabica n. sp. (Microsporidia), infecting the marine fish Epinephelus polyphekadion from the Red Sea

A new microsporidian species, Glugea arabica n. sp., is reported infecting the intestinal wall of the marine teleost Epinephelus polyphekadion (=microdon) collected from the Red Sea coast off Saudi Arabia, and described on the basis of microscopic and molecular procedures. Spherical blackish xenomas formed parasitophorous vacuoles completely packed with several parasitic developmental stages, including spores. The nuclei were monokaryotic in all developmental stages. Spores were ellipsoidal to pyriform and measured 6.3 ± 0.3 (5.9–6.6) μm in length and 3.3 ± 0.4 (2.9–3.7) μm in width. A lamellar polaroplast surrounded the uncoiled portion of the polar filament, which extended into the spore's posterior pole and formed 27–29 coils organized in three or four rows. The posterior vacuole, located at the spore's posterior pole, appeared surrounded by the polar filament coils and displayed an irregular matrix composed of light material, in which was located the posterosome. Molecular analysis of the rRNA genes, including the ITS region, was performed using maximum parsimony, neighbor-joining and maximum likelihood methodologies. The ultrastructural features observed, in combination with the molecular data analysed, suggests the parasite to be a new species of the genus Glugea.     

Molecular data and phylogenetic analysis of Myxobolus pseudonobilis n. sp. infecting the gill filaments of silver carp,Hypophthalmichthys molitrix Valenciennes, 1844

In the present study, we combined morphological and phylogenetic methods to characterize Myxobolus pseudonobilis n. sp. infecting Hypophthalmichthys molitrix Valenciennes, 1844 from Chongqing, China. The morphology and molecular characteristics of M. pseudonobilis n. sp. were distinct from those of other previously described Myxobolus species. Mature myxospores were ovoid in frontal view with spore dimensions of 10.0 ± 0.4 (9.3–10.9) μm in length and 8.5 ± 0.2 (7.9–9.0) μm in width. Two polar capsules occupying approximately half of the myxospore length were unequal in size. The larger polar capsule containing 6 to 7 filament coils measured 5.2 ± 0.3 (4.5–5.8) μm in length and 3.6 ± 0.2 (3.2–3.9) μm in width, while the smaller capsule with 4 to 5 filament coils measured 3.9 ± 0.3 (3.0–4.4) μm in length and 2.5 ± 0.3 (2.1–3.6) μm in width. The comparison of molecular characteristics demonstrated similarities and genetic distances of 18S rDNA sequences of 95.19% - 98.20% and 1.82% - 5.46%, respectively, between M. pseudonobilis n. sp. and its morphologically similar species, and secondary structures were also distinctly different. Moreover, phylogenetic analysis showed that M. pseudonobilis n. sp. was clustered with other myxobolids possessing spores with a blunt anterior end and branched independently. In addition, the morphology of myxosporeans as an important indicator was discussed.     

Levothyroxine Replacement In Obese Hypothyroid Females After Total Thyroidectomy

Objective: Levothyroxine (LT4) replacement in hypothyroid obese patients is poorly understood. We assessed whether the LT4 regimen required to achieve euthyroidism differs between nonobese and obese hypothyroid females.Methods: We retrospectively identified nonobese and obese females who received LT4 starting with a standard dose of 1.6 μg/kg after total thyroidectomy for preoperative diagnosis of benign goiter. We examined the association between LT4 dosage required to achieve euthyroid state (thyroid-stimulating hormone [TSH] 0.4–2.5 mIU/L) and patient characteristics using linear regression models with and without adjustment for age, ethnicity, medication use, and postoperative hypoparathyroidism.Results: We identified 32 females (15 nonobese/17 obese) who achieved euthyroid state. Obese patients weighed more (104.1 ± 22.5 vs. 64.9 ± 10.0 kg, P<.0001) and required a higher final LT4 than nonobese (146 ± 38 vs. 102 ± 12 μg, P = .0002) but LT4 requirements per kg total body weight (TBW) were similar (1.60 ± 0.29 vs. 1.42 ± 0.38 μg/kg, P = .15). LT4 dose per kg ideal body weight (IBW) was higher in obese than in nonobese females (2.62 ± 0.67 vs. 1.88 ± 0.28 μg/kg, P = .0004) and this difference persisted after adjustments (P<.05). During LT4 titration, 47% and 20% of obese and nonobese patients had subnormal TSH episodes, respectively (P = .11). After taking LT4 compliance, malabsorption, and competing medication use into consideration, we found marked LT4 dose variability in obese patients. Patients who needed a mean daily LT4 dose ≤150 mg (124 ± 16 μg/day) compared with >150 μg (198 ± 4 μg/day) demonstrated lower LT4 per TBW (1.25 ± 0.18 vs. 1.84 ± 0.43 μg/kg, P = .03) and IBW (2.28 ± 0.47 vs. 3.44 ± 0.18 μg/kg, P<.0001), respectively.Conclusion: The standard approach to LT4 replacement in obese and nonobese females after thyroidectomy is imprecise. Mean daily LT4 doses in obese and nonobese patients were similar if expressed per kg TBW, though there was variability in the final LT4 among obese patients. We suggest initiating LT4 at a dose lower than that routinely recommended in obese females.Abbreviations:AACE = American Association of Clinical EndocrinologistsATA = American Thyroid AssociationBMI = body mass indexIBW = ideal body weightLT4 = levothyroxineTBW = total body weightTSH = thyroid-stimulating hormone     

Glomerella truncata sp. nov., the teleomorph of Colletotrichum truncatum

Anthracnose of lentil, caused by Colletotrichum truncatum is a serious threat to lentil (Lens culinaris) grown in western Canada. The teleomorph stage of this pathogen was induced to form under laboratory conditions. Random pairing of single conidium isolates enabled the identification of fertile isolates. The individual isolates of this fertile pair were crossed with 14 other isolates, and all isolates were also incubated alone. Self-sterility was observed for all 16 isolates tested. Three isolates did not produce perithecia with either tester isolate, and none of the isolates tested produced perithecia with both tester isolates. Perithecia were brown–black, superficial, solitary or in small groups, obpyriform to ovate or ampulliform, 200–520 × 110–320 μm (mean: 350 × 200 μm). Asci were cylindrical, narrowing slightly at the apex, unitunicate, evanescent, 53–142 × 5–14 μm (mean: 90 × 8 μm), and contained eight ascospores. Ascospores were hyaline, aseptate, oblong, 12–20 × 5–8 μm (mean: 15.7–6.7 μm). The characteristics agree with those described for the genus Glomerella, and the species was named G. truncata sp. nov. The morphology of the new species is compared with that of other species in the genus, and future research on G. truncata is described.     

Sarcocystis tupaia,sp. nov., a new parasite species employing treeshrews (Tupaiidae,Tupaia belangeri chinensis) as natural intermediate hosts

The range of vertebrates that serve as intermediate hosts for parasites in the genus Sarcocystis remains incompletely defined. Here, we provide the first report of infections in treeshrews, describe the morphology of encysted parasites using light and transmission electron microscopy, and place this agent within a phylogenetic context by sequencing and comparing its 18 S ribosomal DNA to that of related parasites. Muscle infections were diagnosed in four of 45 wild treeshrews captured in the vicinity of Kunming, Yunnan Province, Mainland China. Thread-like cysts (10.773 ± 2.411 mm in length, 0.106 ± 0.009 mm in width) had walls (0.538–0.746 µm thick) that lacked perpendicular protrusions. The interior of the cyst was packed full with cyst merozoites, the shape of which was typical of Sarcocystis. The primary cyst wall consisted of a thin membrane supported by osmiophilic material, 31–60 nm in thickness. The ground substance was about 105–526 nm thickness. Cysts conformed to typical of ‘type 1’ sarcocysts. Freshly examined and frozen specimens did not differ in their cyst wall structure, however, the appearance of bradyzoites did differ: the conoid, rhoptries and micronemes were all visible in fresh bradyzoites; in stored bradyzoites, by contrast, the rhoptries appeared smaller, and although the conoid was visible, the micronemes were not. 18 S rRNA gene was distinct from any previously reported sequence in GenBank. Their genetic and morphological uniformity suggest that these parasites, derived from treeshrews, represent a single biological species, Sarcocystis tupaia, sp. nov.     

Design,synthesis, and docking studies of phenylpicolinamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety as c-Met inhibitors

Four series of phenylpicolinamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety (12a–e, 13a–f, 14a–f and 15a–i) were designed, synthesized and evaluated for the IC₅₀ values against three cancer cell lines (A549, PC-3 and MCF-7) and c-Met kinase. Five selected compounds (13b, 15b, 15d, 15e and 15f) were further evaluated for the activity against HepG2 and Hela cell lines. Eighteen of the compounds showed excellent cytotoxicity activity and selectivity with the IC₅₀ valuables in single-digit μM to nanomole range. Seven of them are equal to more active than positive control Foretinib against one or more cell lines. The most promising compound 15f showed superior activity to Foretinib, with the IC₅₀ values of 1.04 ± 0.11 μM, 0.02 ± 0.01 μM and 9.11 ± 0.55 μM against A549, PC-3 and MCF-7 cell lines, which were 0.62 to 19.5 times more active than Foretinib (IC₅₀ values: 0.64 ± 0.26 μM, 0.39 ± 0.11 μM, 9.47 ± 0.22 μM), respectively. Structure–activity relationships (SARs) and docking studies indicated that replacement of quinoline nucleus of the previous active compounds with 1H-pyrrolo[2,3-b]pyridine moiety maintained even improved the potent cytotoxic activity. The results suggested that the introduction of fluoro atoms to the aminophenoxy part of target compounds or the phenyl group of pyrimidine substituted on C-4 position was benefit for the activity.     

Syntheses of 4,6-dihydroxypyrimidine diones,their urease inhibition,in vitro,in silico,and kinetic studies

A library of 4,6-dihydroxypyrimidine diones (1–35) were synthesized and evaluated for their urease inhibitory activity. Structure-activity relationships, and mechanism of inhibition were also studied. All compounds were found to be active with IC₅₀ values between 22.6 ± 1.14–117.4 ± 0.73 µM, in comparison to standard, thiourea (IC₅₀ = 21.2 ± 1.3 µM). Kinetics studies on the most active compounds 2–7, 16, 17, 28, and 33 were performed to investigate their modes of inhibition, and dissociation constants K_i. Compounds 2, 3, 7, 16, 28, and 33 were found to be mixed-type of inhibitors with K_i values in the range of 7.91 ± 0.024–13.03 ± 0.013 µM, whereas, compounds 4–6, and 17 were found to be non-competitive inhibitors with K_i values in the range of 9.28 ± 0.019–13.05 ± 0.023 µM. In silico study was also performed, and a good correlation was observed between experimental and docking studies. This study is continuation of our previously reported urease inhibitory activity of pyrimidine diones, representing potential leads for further research as possible treatment of diseases caused by ureolytic bacteria.     

Multi-channel electromyography during maximal isometric and dynamic contractions

Motor unit behavior differs between contraction types at submaximal contraction levels, however is challenging to study during maximal voluntary contractions (MVCs). With multi-channel surface electromyography (sEMG), mean physiological characteristics of the active motor units can be extracted. Two 8-electrode sEMG arrays were attached on biceps brachii muscle (one on each head) to examine behavior of sEMG variables during isometric, eccentric and concentric MVCs of elbow flexors in 36 volunteers.On average, isometric (364 ± 88 N) and eccentric (353 ± 74 N) MVCs were higher than concentric (290 ± 73 N) MVC (p < 0.001). Mean muscle fiber conduction velocity (CV) was highest during eccentric MVC (4.42 ± 0.49 m/s) than concentric (4.25 ± 0.49 m/s, p < 0.01) and isometric (4.14 ± 0.45 m/s, p < 0.001) MVCs. Furthermore, eccentric MVC showed lower sEMG amplitude at the largest elbow joint angles (120–170°) and higher CV at the smallest (70–150°) elbow joint angles (p < 0.05–0.001) than concentric MVC.The differences in CV and sEMG amplitude between the MVCs suggest that the control strategy of motor units differs between the contraction types during MVCs, and is dependent on the muscle length between the dynamic MVCs.     

Anti-inflammatory components of Euphorbia humifusa Willd.

Two new compounds, euphorbinoside (1) and dehydropicrorhiza acid methyl diester (2), along with 24 known compounds (3–26) were isolated from Euphorbia humifusa Willd. The effects of these compounds on soluble epoxide hydrolase (sEH) inhibitory activity were evaluated. Flavonoid compounds (10–21) exhibited high sEH inhibitory activity. Among them, compounds 12, 13, and 19 greatly inhibited sEH enzymatic activity, with IC₅₀ values as low as 18.05 ± 1.17, 18.64 ± 1.83, and 17.23 ± 0.84 μM, respectively. In addition, the effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compounds 3–6, 8, 18, 20–23, and 25–26 inhibited the production of both NO and TNF-α, with IC₅₀ values ranging from 11.1 ± 0.9 to 45.3 ± 1.6 μM and 14.4 ± 0.5 to 44.5 ± 1.2 μM, respectively.     

Copper,zinc superoxide dismutase of Curcuma aromatica is a kinetically stable protein

This study details on cloning and characterization of Cu,Zn superoxide dismutase (Ca–Cu,Zn SOD) from a medicinally important plant species Curcuma aromatica. Ca–Cu,Zn SOD was 692 bp with an open reading frame of 459 bp. Expression of the gene in Escherichia coli cells followed by purification yielded the enzyme with K_m of 0.047 ± 0.008 μM and V_max of 1250 ± 24 units/mg of protein. The enzyme functioned (i) across a temperature range of −10 to +80 °C with temperature optima at 20 °C; and (ii) at pH range of 6–9 with optimum activity at pH 7.8. Ca–Cu,Zn SOD retained 50% of the maximum activity after autoclaving, and was stable at a wide storage pH ranging from 3 to 10. The enzyme tolerated varying concentrations of denaturating agent, reductants, inhibitors, trypsin, was fairly resistant to inactivation at 80 °C for 180 min (k_d, 6.54 ± 0.17 × 10⁻³ min⁻¹; t_1/2, 106.07 ± 2.68 min), and had midpoint of thermal transition (T_m) of 70.45 °C. The results suggested Ca–Cu,Zn SOD to be a kinetically stable protein that could be used for various industrial applications.     

Synthesis,and docking studies of phenylpyrimidine-carboxamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety as c-Met inhibitors

Four series of phenylpyrimidine-carboxamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety (14a–e, 15a–g, 16a–e and 17a–g) were designed, synthesized and evaluated for the IC₅₀ values against three cancer cell lines (A549, PC-3 and MCF-7). Four selected compounds (15e, 16a–b and 17a) were further evaluated for the activity against c-Met kinase, HepG2 and Hela cell lines. Most of the compounds showed excellent cytotoxicity activity and selectivity with the IC₅₀ valuables in single-digit μM to nanomole range. Eleven of them are equal to more active than positive control Foretinib against one or more cell lines. The most promising compound 15e showed superior activity to Foretinib against A549, PC-3 and MCF-7 cell lines, with the IC₅₀ values of 0.14 ± 0.08 μM, 0.24 ± 0.07 μM and 0.02 ± 0.01 μM, which were 4.6, 1.6 and 473.5 times more active than Foretinib (0.64 ± 0.26 μM, 0.39 ± 0.11 μM, 9.47 ± 0.22 μM), respectively. Structure–activity relationships (SARs) and docking studies indicated that the replacement of phenylpicolinamide scaffold with phenylpyrimidine fragment of the target compounds was benefit for the activity. What’s more, the introduction of fluoro atom to the aminophenoxy part played no significant impact on the activity and any substituent group on aryl group is unfavourable for the activity.     

Effects of temperature,salinity and their interaction on growth of benthic dinoflagellates Ostreopsis spp. from Thailand

Benthic dinoflagellates Ostreopsis spp. are known as producers of palytoxin and its analogs, resulting occasionally in human health problems worldwide. Although distribution of Ostreopsis spp. along the Thai coasts has been reported, little is known about their growth characteristics. To discuss the bloom dynamics of Ostreopsis spp. in Thailand, first we tested four kinds of media to optimize growth conditions and then clarified the effects of temperature, salinity and temperature–salinity interaction on the growth of strains of the O. cf. ovata Thailand subclade, O. cf. ovata South China Sea subclade, Ostreopsis sp. 6 and Ostreopsis sp. 7. We showed that the f/2 medium was a suitable medium which gave the highest cell yields for all the strains tested. The strains of the O. cf. ovata Thailand subclade, O. cf. ovata South China Sea subclade and Ostreopsis sp. 6 grew in the temperature range 20–32.5 °C, whereas the strain of Ostreopsis sp. 7 grew in 20–30 °C. The semi-optimal temperature ranges (≧80% of the maximal growth rate) for the former three strains were 22.7–27.4 °C, 27.9–30.8 °C and 23.5–26.4 °C, respectively, whereas that of the latter strain was 23–27.2 °C. The optimal temperature for the O. cf. ovata South China Sea subclade was 30 °C, whereas for the others it was 25 °C. All the Ostreopsis strains tested could grow in a salinity range of 20–40. The semi-optimal salinities for the O. cf. ovata Thailand subclade, O. cf. ovata South China Sea subclade Ostreopsis sp. 6 and Ostreopsis sp. 7 were 28.7–35, 23.8–30.8, 29.8–36 and 28–36, respectively. The optimal salinities for the O. cf. ovata Thailand subclade and O. cf. ovata South China Sea subclade were 30 and 25, respectively, whereas for Ostreopsis sp. 6 and Ostreopsis sp. 7 it was 35. In this study, our results suggested that the optimal and tolerable temperature–salinity conditions differ among the Thai Ostreopsis species/clades/subclades. Tolerances of the O. cf. ovata Thailand subclade, O. cf. ovata South China Sea subclade and Ostreopsis sp. 6 to the high temperature of 32.5 °C may allow these organisms to be distributed in the tropical areas, where the water temperature often reaches >30 °C.     

New bioactive derivatives of nonactic acid from the marine Streptomyces griseus derived from the plant Salicornia sp.

Three new compounds, butyl homononactate (5), butyl nonactate (6), 8-actyl homononactic acid (7), along with four known compounds homononactic acids (1), nonactic acid (2), homononactyl nonactate (3), homononactyl homononactate (4) were isolated from the marine Streptomyces griseus RSH0407, derived from the plant Salicornia sp., Chenopodiaceae. Their structures were elucidated by extensive spectroscopic techniques and by comparison with data reported in the literature. The absolute configuration of 3 was first reported by using X-ray copper radiation. Compound 5 exhibited cytotoxic activities against the HCT-8, A2780, BGC-823, BEL-7402, and A549 cell lines in vitro, with IC₅₀ values of 2.87 ± 0.20, 4.90 ± 0.30, 2.19 ± 0.32, 5.07 ± 0.23 and 1.78 ± 0.18 μM, respectively, and compounds 4–7 showed weak antibacterial activities against four bacterials respectively.     

Factors influencing the return of submerged plants to a clear-water,shallow temperate lake

Lack of submerged vegetation was studied in a small, shallow, alkaline, clear-water lake with high nitrate concentration (mean 9 mg NO₃–N L⁻¹) and profuse filamentous green algae (FGA) (mainly Spirogyra sp.). A laboratory microcosm and two lake enclosure experiments were carried out using Elodea nuttallii (Planchon) St John. E. nuttallii grew about 1.7 times as well in sediment from its place of origin compared with sediment from the lake. Differential water quality had no effect, and neither sediment nor water prevented growth in the lake. Nutrient addition reduced plant growth by more than 55% because of shading from epiphytic filamentous green algae (shoot dry weight versus epiphytic algal dry weight, r = −0.491, P < 0.05). Transplanted Elodea plants grew better in enclosures in the lake than in laboratory conditions with lake water and sediment (P < 0.001, t-test). Rare Elodea individuals in the lake indicate the presence of plant propagules in the lake sediment, but excessive growth of filamentous green algae (summer mean 3.2 g dry weight m⁻²) significantly hamperd plant growth (shoot length reduced from 29 ± S.E.M. 1 to 25 ± 1 cm) and bird herbivory significantly reduced survival (from 82 ± 7 to 40 ± 6%) and shoot growth (from 78 ± 6 to 18 ± 5 cm) and thus eliminates establishment of even modest plant beds. Fish disturbance and sediment stability were not important. Restoration of submerged plants may require reduction of nitrate input, control of filamentous green algae and protection from birds.     

Synthesis and antioxidant evaluation of (S,S)- and (R,R)-secoisolariciresinol diglucosides (SDGs)

Secoisolariciresinol diglucosides (SDGs) (S,S)-SDG-1 (major isomer in flaxseed) and (R,R)-SDG-2 (minor isomer in flaxseed) were synthesized from vanillin via secoisolariciresinol (6) and glucosyl donor 7 through a concise route that involved chromatographic separation of diastereomeric diglucoside derivatives (S,S)-8 and (R,R)-9. Synthetic (S,S)-SDG-1 and (R,R)-SDG-2 exhibited potent antioxidant properties (EC₅₀ = 292.17 ± 27.71 μM and 331.94 ± 21.21 μM, respectively), which compared well with that of natural (S,S)-SDG-1 (EC₅₀ = 275.24 ± 13.15 μM). These values are significantly lower than those of ascorbic acid (EC₅₀ = 1129.32 ± 88.79 μM) and α-tocopherol (EC₅₀ = 944.62 ± 148.00 μM). Compounds (S,S)-SDG-1 and (R,R)-SDG-2 also demonstrated powerful scavenging activities against hydroxyl [natural (S,S)-SDG-1: 3.68 ± 0.27; synthetic (S,S)-SDG-1: 2.09 ± 0.16; synthetic (R,R)-SDG-2: 1.96 ± 0.27], peroxyl [natural (S,S)-SDG-1: 2.55 ± 0.11; synthetic (S,S)-SDG-1: 2.20 ± 0.10; synthetic (R,R)-SDG-2: 3.03 ± 0.04] and DPPH [natural (S,S)-SDG-1: EC₅₀ = 83.94 ± 2.80 μM; synthetic (S,S)-SDG-1: EC₅₀ = 157.54 ± 21.30 μM; synthetic (R,R)-SDG-2: EC₅₀ = 123.63 ± 8.67 μM] radicals. These results confirm previous studies with naturally occurring (S,S)-SDG-1 and establish both (S,S)-SDG-1 and (R,R)-SDG-2 as potent antioxidants and free radical scavengers for potential in vivo use.     

GLP-1(32–36)amide,a novel pentapeptide cleavage product of GLP-1, modulates whole body glucose metabolism in dogs

We have previously demonstrated in human subjects who under euglycemic clamp conditions GLP-1(9–36)amide infusions inhibit endogenous glucose production without substantial insulinotropic effects. An earlier report indicates that GLP-1(9–36)amide is cleaved to a nonapeptide, GLP-1(28–36)amide and a pentapeptide GLP-1(32–36)amide (LVKGR amide). Here we study the effects of the pentapeptide on whole body glucose disposal during hyperglycemic clamp studies. Five dogs underwent indwelling catheterizations. Following recovery, the dogs underwent a 180 min hyperglycemic clamp (basal glucose +98 mg/dl) in a cross-over design. Saline or pentapeptide (30 pmol kg⁻¹ min⁻¹) was infused during the last 120 min after commencement of the hyperglycemic clamp in a primed continuous manner. During the last 30 min of the pentapeptide infusion, glucose utilization (M) significantly increased to 21.4 ± 2.9 mg kg⁻¹ min⁻¹compared to M of 14.3 ± 1.1 mg kg⁻¹ min⁻¹ during the saline infusion (P = 0.026, paired t-test; P = 0.062, Mann–Whitney U test). During this interval, no significant differences in insulin (26.6 ± 3.2 vs. 23.7 ± 2.5 μU/ml, P = NS) or glucagon secretion (34.0 ± 2.1 vs. 31.7 ± 1.8 pg/ml, P = NS) were observed. These findings demonstrate that under hyperglycemic clamp studies the pentapeptide modulates glucose metabolism by a stimulation of whole-body glucose disposal. Further, the findings suggest that the metabolic benefits previously observed during GLP-1(9–36)amide infusions in humans might be due, at least in part, to the metabolic effects of the pentapeptide that is cleaved from the pro-peptide, GLP-1(9–36)amide in the circulation.     

Higher Growth Hormone Levels are Associated with Erectile Dysfunction in Male Patients With Acromegaly

Objective: To investigate in vivo correlates of erectile dysfunction (ED) in male patients with acromegaly.Methods: Fifty-one male patients with acromegaly were assessed by the International Index of Erectile Function-5 and Acromegaly Quality of Life (Acro-QoL) questionnaires. The measurement of serum nitric oxide (NO) were performed in patients and age-matched nonacromegalic controls.Results: Among 51 patients analyzed, 32 (62.7%) had ED. Patients with ED showed lower Acro-QoL scores regarding global (69.8 ± 17.7 versus 79.4 ± 11.2; P = .035) and personal relationship dimensions (59.6 ± 22.1 versus 76.8 ± 17.6; P = .012) than non-ED patients. ED patients were older (44.5 ± 11.2 years versus 33.2 ± 8.5 years; P = .04) and showed higher growth hormone (GH) levels (15.5 μg/L &lsqb;interquartile range of 9.5 to 34.5 μg/L] versus 5.9 μg/L &lsqb;interquartile range of 3.4 to 13.9 μg/L]; P = .001) compared to non-ED patients. The cutoff values for identifying ED were 7.9 μg/L for random GH and 5.3 μg/L for GH nadir after oral administration of 75 g of glucose. There was no significant difference in total testosterone levels between the two groups (6.36 ± 4.24 nmol/L versus 9.54 ± 5.50 nmol/L; P = .299). The NO levels in patients with acromegaly were significantly lower than those in nonacromegalic controls (8.77 ± 1.78 μmol/L versus 19.19 ± 5.02 μmol/L, respectively; P = .049). Furthermore, the NO levels were even lower in ED patients than those in non-ED patients (5.14 ± 0.98 μmol/L versus 12.09 ± 3.44 μmol/L; P = .027).Conclusion: Our study showed that ED is prevalent in male acromegalic patients and may be associated with systemic endothelial dysfunction induced by excessive GH. Further studies investigating the mechanism of GH and ED are required.Abbreviations: Acro-QoL = Acromegaly Quality of Life; ED = erectile dysfunction; FSH = follicle-stimulating hormone; GH = growth hormone; IGF-1 = insulin-like growth factor 1; IIEF-5 = international index of erection function-5; LH = luteinizing hormone; MRI = magnetic resonance imaging; NO = nitric oxide; OGTT = oral glucose tolerance test; QoL = quality of life; ROC = receiver operating characteristic