The role of elective perioperative dialysis in nondialysis renal failure patients.

BACKGROUND: Patients with renal insufficiency represent a difficult group. They show an increased morbidity and mortality after heart surgery. Nondialysis chronic kidney disease patients show higher mortality than patients receiving chronic dialysis. Their management is not standardized. This study was undertaken to determine whether elective perioperative dialysis in these patients improved outcomes. METHOD: A retrospective review of records of nondialysis chronic kidney disease patients was carried out. Patients who were not dialyzed before surgery (group A, n = 28) were compared with a propensity-matched group of patients (group B, n = 28) who received elective dialysis preoperatively for their baseline characteristics and outcomes of their heart surgery. RESULTS: Patients who received elective dialysis in the perioperative period (group B) showed fewer neurologic complications (p = 0.004), shorter postoperative length of stay (p = 0.053), fewer gastrointestinal complications (p = 0.051), and fewer major adverse events (p = 0.013). Multiorgan failure and discharge to an extended care facility were also less frequent in group B, although this did not reach statistical significance. CONCLUSIONS: Nondialysis renal failure patients, particularly those with higher creatinine concentrations, may benefit from elective perioperative dialysis in terms of decreased rates of complications and shorter postoperative length of stay.

By-side PCDD/Fs in technical PCB formulations of Kanechlor series.

The Japanese Kanechlor technical PCB formulations such as KC-300, KC-400, KC-500, KC-600 and KC-1000 have been examined for possible contamination with by-side PCDD/Fs. 75 PCDDs and 135 PCDF have been determined using isotope dilution, separation and enrichment on silica gel impregnated with activated carbon, and final HRGC/HRMS measurement. MonoCDDs to OCDD were absent in KC-300, KC-600 and KC-1000. Tetra- and PentaCDDs occurred at > 1 ng/g in KC-400 and KC-500. The Kanechlors were contaminated with nearly all 135 PCDFsw. In parallel with an increasing degree of chlorination of a particular Kanechlor formulation examined increased also the content of more chlorinated PCDFs. In term of total dioxin-like toxicity and TEQ loads the KC-500 contained highly toxic PCDD/Fs at 270 ng TEQ/g and followed by KC-400 with 269 ng TEQ/g, KC-600 with 188 ng TEQ/g, KC-1000 with 164 ng TEQ/g and KC-300 with 79 ng TEQ/g. From 99.5 to 100% of PCDD/Fs toxicity found in the Kanechlors was from PCDFs.

Multivariate analysis of identity of imported technical PCN formulation.

Chloronaphthalenes form a class of compounds consisting of 8 CN homologue groups and altogether of 75 congeners, which used have been most extensively in 1930--1950. An investigation have been performed on the possible origin of unidentified by name technical chloronaphthalene formulation unlawfully imported recently from the United Kingdom to Japan. Principal component analysis (PCA) and Cluster Analysis of chloronaphthalene congener isomer-specific and homologue classes' compositional HRGC/HRMS data of imported CN formulation and of certain brands of technical CN formulation called Halowax (Halowax 1000, 1001 and 1031) enabled to identify that unnamed product is not Halowax 1001. A less accurate multivariate examination based on CN homologue classes patter did indicate on large similarity between unlawfully imported technical CN formulation and Halowax 1001 (manufactured by the Koppers Ind. Co., USA), while a more accurate based on CN congeners pattern differentiated them as to of various origin mixtures. Based on chlorine content of imported CN formulation (50-52%) and its no similarity to Halowax 1001 it seems reasonable to conclude that unnamed CN mixture examined could be a sample of stockpiled Seekay wax R93.

HRGC/HRMS analysis of chloronaphthalenes in several batches of Halowax 1000, 1001, 1013, 1014 and 1099.

Chloronaphthalene (CN) congeners and homologue groups have been quantified in up to three batches of several types of technical CN formulations of the Halowax series (Halowax 1031, 1000, 1001, 1013, 1014 and 1099), to elucidate possible batch-to-batch compositional variations. Using isotope dilution and HRGC/HRMS a relatively large variation in CN congeners and homologues composition among the batches of particular types of the Halowax formulations could be noted, and also when compared to the composition declared by the manufacturer. Depending on the type of the Halowax formulation and its batch in total up to 54 peaks from chloronaphthalenes (Agilent Ultra 2 liquid phase), which represented 70 of 75 CN congeners theoretically possible, could be found in these mixtures. These congeners represented all CN homologue groups from mono- to octaCN but some co-eluted. A co-eluting congeners were such as: 1,4-/1,6- (nos. 5/7), 1,5-/2,7- (nos. 6/12), 2,6-1,7- (nos. 11/8) of diCNs; 1,3,6-/1,3,5- (nos. 20/19), 1,3,7-/1,4,6- (nos. 23/24), 1,6,7-/2,3,6- (nos. 25/26) of triCNs; 1,2,5,7-/1,2,4,6-/1,2,4,7- (nos. 37/33/34), 1,3,6,8-/1,2,5,6- (nos. 45/36), 1,2,3,5-/1,3,5,8- (nos. 28/43), 1,2,3,4-/1,2,3,7- (nos. 27/30), 1,2,5,8-/1,2,6,8- (nos. 38/40) of tetraCNs; 1,2,3,5,7-/1,2,4,6,7- (nos. 52/60), 1,2,3,5,8-/1,2,3,6,8- (nos. 53/55) of pentaCNs; 1,2,3,4,6,7-/1,2,3,5,6,7- (nos. 66/67), 1,2,3,4,5,7-/1,2,3,5,6,8- (64/68) and 1,2,4,5,6,8-/1,2,4,5,7,8- (nos. 71/72) of hexaCNs. Absent in the Halowaxes were CN congeners such as 1,3,8-triCN (no. 22) (<0.0002 mg/g), 1,3,6,7-tetraCN (no. 44), 1,2,3,6-TetraCN (no. 29), 1,2,3,6,7-pentaCN (no. 54) and 1,2,3,6,7,8-hexaCN (no. 70) (<0.0005 mg/g).

Chloronaphthalenes composition of several batches of Halowax 1051.

Halowax 1051 is the highest chlorinated technical chloronaphthalene mixture among seven known formulations of the Halowax series. Octa- and heptaCN homologue groups are the main CN constituents of Halowax 1051 with declared 90% and 10% contents, respectively. In this study, using an isotope dilution technique and HRGC/HRMS, octaCN and heptaCNs contents of six batches of Halowax 1051 were between 82-93% and 6.2-17%, respectively. Also mono- to hexaCNs were found in Halowax 1051, and their content more or less varied according to the batch; also, the abundance of a particular CN congeners varied. Tetra-, penta- and hexaCNs have been found in all six batches of Halowax 1051 examined, and their contents varied between 0.0024-0.77%, 0.031-0.22%, and 0.21-0.82%, respectively. TriCNs have been found in three of six batches, and mono- and diCNs in two of six batches with 0.0020-0.40, 0.0017-0.25 and 0.0012-0.34% for positive findings, respectively. 2,3-DiCN (no. 10), 1,8-diCN (no. 9) at < 0.0002 mg/g, 1,6,7-/2,3,6-triCNs (nos. 25/26), 1,3,8-triCN (no. 22) at < 0.0002 mg/g, 1,3,6,7-tetra (no. 44), 1,2,3,6-tetra- (no. 29), 1,2,7,8-tetraCN (no. 41) and 1,2,3,6,7,9-hexaCN (no. 70) at < 0.0005 mg/g have not been found in Halowax 1051.

By-side chlorobenzenes and chlorophenols in technical chlorobiphenyl formulations of Aroclor 1268, Chlorofen, Clophen T 64, Kanechlor 600, and Kanechlor 1000.

All 19 possible chlorophenol (CPh) and 12 chlorobenzene (CBz) congeners as potential impurities or additive were quantified in a relatively highly chlorinated type of technical chlorobiphenyl (CB) mixtures of Aroclor 1268, Chlorofen, Clophen T 64, Kanechlor 600, and Kanechlor 1000 using isotope dilution technique and HRGC/HRMS. The total CBzs content of Aroclor 1268, Chlorofen and Clophen T 64, Kanechlor 600, and Kanechlor 1000 was 0.039, 0.5, 230, 0.068, and 400 mg/g, respectively, while of CPhs was < 0.007, 0.48, 10, 0.093, and 0.98 microg/g. All 12 congeners of chlorobenzene could be quantified in all the formulations examined, but their proportions varied largely. It seems that stockpiles of technical chlorobiphenyl formulations and hazardous wastes containing CBs, both with added and/or by-side CBzs are also a somehow forgotten source of environmental contamination with those environmentally relevant compounds. No CPhs were found in Aroclor 1268 (< 7 ng/g). 2-MoCPh, 2,6-DiCPh, 3,5-DiCPh, 3,4,5-TrCPh, and 2,3,4,5,6-PeCPh were absent (< 1- < 20 ng/g) in Chlorofen and Clophen T 64, while other chlorophenol congeners were found at concentration from 7.4 to 130 and from 9.9 to 8,800 ng/g, respectively. Then, 3- and 4-chlorophenol, which co-eluted, were main contributors (88%) to the total CPhs content of Clophen T 64, while 2,3,4,6-TeCPh with 27% abundance was a major congener among CPhs in Chlorofen. Then, 2,4,6-TrCPh was the most abundant congener in Kanechlor 600, while 2,4,5-TrCPh was the most abundant congener in Kanechlor 1000.

Chlorobiphenyl constituents of Aroclor 1268, Chlorofen, Clophen T 64, KC-600, and KC-1000 technical formulations.

All 209 chlorobiphenyls (CBs) theoretically possible and potentially present in relatively highly chlorinated types of technical CB formulations of Aroclor 1268, Chlorofen, Clophen T 64, KC-600, and KC-1000 have been quantified using isotope dilution techniques and high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). CB constituents of Aroclor 1268, Chlorofen, Clophen T 64, KC-600, and KC-1000 could be separated, detected, identified and quantified as "bulk CBs," using a capillary column (60 m length x 0.25 mm i.d.) coated by 8% phenyl polycarborane-siloxane (HT-8PCB, SGE, Australia) liquid phase for GC coupled to HRMS, into 111, 78, 126, 137, and 148 peaks, respectively, which covered 140, 100, 158, 169, and 180 possible CB congeners. 87, 60, 99, 110, and 121 peaks represented single CB congeners in Aroclor 1268, Chlorofen, Clophen T 64, KC-600, and KC-1000, respectively, while 34, 18, 27, 27, and 27 peaks represented 53, 40, 59, 59, and 59 co-eluting CBs. After enrichment procedures using multilayer silica beds, alumina beds, and carbon-impregnated silica beds in glass columns, all four planar non-ortho CBs and all eight mono-ortho CBs (but with the exception of CB no. 123 in Chlorofen) could be quantified in all five technical CB formulations examined. The planar non- and mono-ortho CBs content of Aroclor 1268, Chlorofen, Clophen T 64, KC-600 and KC-1000 were 6.2, 7.0, 47, 120, 470 mu g/g and 220, 410, 34,000, 12,000, 5900 mu g/g, respectively, and their 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents (2,3,7,8-TeCDD TEQs) were 31, 390, 710, 260, 1900 ng-TEQ/g and 35, 99, 5900, 2600, 8900 ng-TEQ/g, and the total 2,3,7,8-TeCDD TEQs of planar CBs were 66, 490, 6600, 2900, and 11,000 ng-TEQ/g.

By-side chlorodibenzo-P-dioxins and chlorodibenzofurans in technical chlorobiphenyl formulations of aroclor 1268, chlorofen, and clophen T 64.

Aroclor 1268, Chlorofen, and Clophen T 64 technical chlorobiphenyl formulations were examined for 75 congeners of chlorodibenzo-p-dioxin (CDD) and 135 congeners of chlorodibenzofuran (CDF) using isotope dilution technique, separation, and enrichment on silica gel impregnated with activated carbon and final high resolution gas chromatography (HRGC)/high resolution mass spectrometry (HRMS) quantification. Three the most highly chlorinated congeners of CDD were found in Aroclor 1268, Chlorofen, and Clophen T 64. In the case of CDF, the number of congeners identified was 108 with 44 coeluting in pairs and 3 in triplicate in Aroclor 1268, 16 with 4 coeluting in pairs in Chlorofen, and 88 with 46 coeluting in pairs and 3 in triplicate in Clophen T 64. The total CDD and CDF concentrations of Aroclor 1268, Chlorofen, and Clophen T 64 were 24, 160, and 8.5 ng/g and 1600,270,000, and 4000 ng/g, respectively. No mono- to hexa-CDDs could be quantified in Aroclor 1268 (<0.03 to <1 ng/g), Chlorofen (<0.07 to <0.3 ng/g), or Clophen T 64 (<0.007 to <2 ng/g), whereas two hepta-CDDs and octa-CDD were found in all three formulations, and Chlorofen was richer in those compounds, followed by Aroclor 1268 and Clophen T 64.

By-side impurities in chloronaphthalene mixtures of the Halowax series: all 135 chlorodibenzofurans.

One hundred twenty five congeners of CDF off 135 theoretically possible were quantified in seven of various type Halowax formulations but still 45 co-eluted under the gas chromatographic conditions applied. The total CDFs concentration of Halowax formulations was between 250 and 16,000 ng/g. The compositional profile of CDF homologue groups of the Halowaxes frequently followed a degree of chlorination of the parent chloronaphthalene mixture and an exception was Halowax 1031. The compositional profile of many isomers of trichlorodibenzofuran, found and often highly abundant, was characteristic to majority of the formulations examined, and each of them demonstrated to have its own pattern but mysterious to explain remained Halowax 1031. In term of dioxin-like toxicity the most potent due to CDFs content was Halowax 1014 with 210 ng TCDD TEQ/g and next was Halowax 1013 with 36 ng TEQ/g, while between 1.3 and 5.0 ng TEQ/g were for other formulations. A tentative estimation made implies that the net total CDFs production due to manufacture of the technical CNs in the XX century could reach an amount between 420 kg (median) and 825 kg (mean), and for most toxic dioxin-like congeners between 705 g (median) and 5700 g (mean) TCDD TEQ, while for the worst case of Halowax 1014 alone scenario it could be 750 kg of the total CDFs and 16 kg of TCDD TEQ for most toxic congeners.

By-side impurities in chloronaphthalene mixtures of the Halowax series: all 75 chlorodibenzo-p-dioxins.

A by-side chlorodibenzo-p-dioxins (CDDs) has been identified as impurity in concentration between 1.5 and 370 ng/g in the Halowax formulations of all type. Halowax 1014 was relatively richer in number of CDD congeners detected when compared to six other CN formulations examined. Amongst the mono- to tri-CDDs, the most prevalent in the Halowaxes were 1- and 2-MoCDD, and especially they were abundant in the formulations of a lower than a higher degree of chlorination. Amongst the tetra- to octaCDD only 1,2,3,4-/1,2,4,6-/1,2,4,9-/ 1,2,3,8-TeCDD, 1,2,3,4,6,7,8-HpCDD and OcCDD were found in all the Halowaxes, and 1,2,3,4,6,7,9-HpCDD remained undetected only in Halowax 1099 and 1013, while most of TeCDDs, PeCDD, and HxCDDs were absent in a majority of the formulations examined. The compositional profile of 1,2,3,4-/1,2,4,6-/1,2,4,9,-/1,2,3,8-TeCDD and OcCDD congeners found in the Halowaxes seem to indicate, that after an initial in situ formation of mono- and di-CDDs during CNs synthesis, a further increase of reaction time, temperature, and pressure can lead to successive chlorination of the already established chlorodibenzo-p-dioxin molecule, and so to enrichment in 1,2,3,4-/ 1,2,4,6-/1,2,4,9,-/1,2,3,8-TeCDD but also OcCDD content for most of the final products obtained. Nevertheless, also due to the co-synthesis of chlorophenols in the Halowaxes, their condensation reactions could also contribute to the formation of CDDs. In term of dioxin-like toxicity the most potent due to CDDs content was Halowax 1014 with 0.95 ng TCDD TEQ/g, and between 0.00068 and 0.058 ng/g were for other formulations. A rough estimation made implies that a net CDDs production due to manufacture of the technical CNs in the XX century could reach an amount between 3.0 and 12.6 kg, while for most toxic dioxin-like constituents between 5.25 and 24 g TCDD TEQ, For the worst case scenario and involvement of Halowax 1014 only the net total CDDs production was estimated to be 1.5 kg, and for highly-toxic congeners 71 g TCDD TEQ. All these figures are much lower when compared to co-production of CDFs.

By-side impurities in chloronaphthalene mixtures of the Halowax series: all 12 chlorobenzenes.

Total chlorobenzene content of the Halowax mixtures ranged from 1100 to 9800 ng/g. A lower chlorinated Halowax 1031 and 1000 were a several times more contaminated with chlorobenzenes than higher chlorinated Halowax 1001, 1099, 1013, 1014, or 1051. Depending on the type of the Halowax mixture the most contributing amongst of chlorobenzene homologue groups were di-, tetra-, penta-, and hexa-CBz. A dominance and specific profile of 1,4-DiCBz, PeCBz, and HCBz were characteristic to Halowax 1001, 1099, 1013, 1014, and 1051, while for other formulation the CBzs profile varied, and 1,2,3,4-TeCBz (Halowax 1031) and 1,4-DiCBz (Halowax 1000) predominated. A steric hindrance effect seems to direct a preferential by-side formation of 1,4-DiCBz and further also of PeCBz and HCBz due to relatively elevated temperature as well as duration time of synthesis for five most chlorinated (49-70 Cl%) chloronaphthalene Halowax formulations.

By-side impurities in chloronaphthalene mixtures of the Halowax series: all 19 chlorophenols.

All seven Halowax formulations examined were contaminated with chlorophenols (CPhs). The total CPhs content of the CN mixtures ranged from 1050 to 34,200 ng/g. The absolute concentration of CPhs decreased with an increase of degree of chlorination (% Cl) of the Halowax 1031 (27%), 1000 (35%), 1001 (49%), and 1099 (51%), respectively, but remained relatively constant for higher chlorinated Halowax 1099 (51%), 1013 (54%), 1014 (59%), and 1051 (70%). 2,4,6-TrCPh and 2,4-DiCPh did contaminated all seven Halowax formulations and PeCPh remained undetected (<90 ng/g) only in Halowax 1099, while less frequently occurred 2,6-DiCPh and followed by 3-/4-MoCPh, 2,5-DiCPh, 2-MoCPh, 2,3-DiCPh, and 2,3,4,6-TeCPh. The CPh congeners such as 3,4-DiCPh, 3,5-DiCPh, 2,3,4-TrCPh, 2,3,5-TrCPh, 2,3,6-TrCPh, 2,4,5-TrCPh, 3,4,5-TrCPh, 2,3,4,5-TeCPh, and 2,3,5,6-TeCPh were undetected in any of the Halowax formulation examined. The profile (%) of higher chlorinated CPh homologues like PeCPh in the Halowaxes followed somehow a degree of chlorination (Cl %) of the parent mixture, i.e., increased from 14, 22, 43, 55, 52 to 80%, respectively, but exception was free of PeCPh the Halowax 1099. And contrary, for a lower chlorinated DiCPhs and TrCPhs their relative proportions decreased but again an exception was Halowax 1099. The fingerprint profiles of 2,4,6-TrCPh, 2,4-DiCPh, and PeCPh, which were usually the most abundant congeners varied and were less consisted when compared to the CPh homologue group profiles, and also more depended on the type of technical Halowax mixture. Due to absence of 2,4,5-TrCPh but presence of 2,4-DiCPh, 2,6-DiCPh, 2,4,6-TrCPh, and PeCPh, which, respectively, are indicative congeners for CPhs obtained by alkaline hydrolysis of chlorobenzenes or phenol chlorination using gaseous chlorine, just co-occurrence of phenol impurity in technical naphthalene is suggested as a solely source of CPhs in the Halowax mixtures.

By-side impurities in chloronaphthalene mixtures of the Halowax series: all 209 chlorobiphenyls.

202 congeners of chlorobiphenyl (CB) with 109 single-resolved compounds and 93 co-eluting, which represented from mono- to deca-CB were quantified as by-side impurities in all seven and of various type the technical chloronaphthalene (CN) formulations of the Halowax series. IUPAC No. 104, 145, 159, 169, 184, 186, and 188 were undetected (<0.05-<0.7 ng/g). The total CBs content of the Halowax formulations ranged between 220 and 640,000 ng/g, and lower chlorinated Halowaxes 1031 (27% Cl) and 1000 (35% Cl) were two to three orders of magnitude more contaminated with CBs than higher chlorinated Halowax 1001, 1099, 1013, 1014, and 1051 (49-70% Cl). The profile of CB homologue groups of the Halowaxes changed and followed somehow a degree of chlorination of the parent CN mixture. For Halowax 1031 and 1000, a decreasing trend in proportion from mono- to deca-CB was evident, while for Halowax 1001, 1099, 1013, 1014, and 1051 the relative proportions between the CB homologue groups varied somehow. Evidently content of lower chlorinated mono- and di-CBs highly decreased and steadily increased tri- to octa-CBs and they become dominating homologues in Halowax formulations in parallel with an increase of the content of higher molecular weight CN constituents, respectively. Among planar non- and mono-ortho CBs, total concentrations in Halowax formulations were detected in the range of 2.0-2600 ng/g, and only 3,3',4,4',5,5'-HxCB (no. 169) was undetected (<0.05ng/g). Detection of by-side CBs in technical Halowaxes demonstrate clearly that those formulations apart from a massive introduction of dioxin-like CNs become in the past also an early source of environmental pollution with CBs, which proceeded for around 20-30 years use of original CB formulations.

Defective morphogenesis and functional maturation in fetal islet-like cell clusters from OLETF rat, a model of NIDDM.

A failure in the compensate proliferation of pancreatic beta-cells, as the primary pathogenic event, has been reported in OLETF rat, a model of NIDDM. The aim of the present study is to define whether the beta-cell defect is attributed to the fetal stage islet development, if so, whether the defect involves down regulation of PDX-1 protein expression. Morphological changes, beta-cell function, and the expression of PDX-1 protein were examined in the cultured fetal islet-like cell clusters (ICCs) from OLETF rats along with their diabetes-resistant control counterpart LETO rats in the presence of 5.5 or 11.1mM glucose for 48, 72, 96, and 120-hr, respectively. We have observed four abnormalities in the ICCs of OLETF rats. First, a defective morphogenesis was noted during the 72 to 120-hr ICC culture, a period characterized by a dramatic increase in both beta-cell and non-beta-cell (alpha, delta, and PP) populations in control rats. This defective morphogenesis was demonstrated by a growth retardation of epithelial stratification and poor development of both beta-cell and non-beta-cell masses along with a parallel decline in relevant islet hormone contents. Second, a functional defect was characterized by failure to response to glucose during the 96 to 120-hr-cultured ICCs. Third, the ultrastructural analysis revealed a significant reduction in the number of secretory granules. Four, Western blot analysis showed a significant decrease of PDX-1 protein expression in the OLETF ICCs cultured in 11.1mM glucose for 48 to 72-hr and in 5.5mM glucose for 120-hr. Therefore, we concluded that during the fetal stage of islet development, OLETF rats exhibit both morphological and functional defects.

Screening of biotransformation products of carvone enantiomers by headspace-SPME/GC-MS.

In the course of our continuing work on transformation of monoterpenes by microorganisms, the biotransformation of (+)- and (-)-carvone was carried out. The metabolites formed during microbial transformations were screened using a simple, rapid and efficient technique: Headspace-solid phase microextraction (SPME)/GC-MS. The results as well as the application of this technique are described.

Microbial transformation of dehydropinguisenol by Aspergillus sp.

Two metabolites were obtained by microbial transformation of a furanosesquiterpene alcohol, dehydropinguisenol, using Aspergillus niger and Aspergillus cellulosae. Their structures were established as 10-oxo-lejeuneapinguisenol and lejeuneapinguisenol on the basis of their spectroscopic data. The latter compound was obtained after 4 and 9 days of incubation with A. cellulosae at 30 degrees C and 25 degrees C, respectively. Aspergillus niger produced both metabolites after 3 and 5 days incubation at 30 degrees C, respectively. A possible pathway for the formation of these compounds is discussed here together with their antimicrobial activity against A. niger and A. cellulosae.

Biotransformation of hinesol isolated from the crude drug Atractylodes lancea by Aspergillus niger and Aspergillus cellulosae.

Biotransformation of the sesquiterpene alcohol hinesol (1) with spasmolytic activity, which was prepared from the rhizome of Atractylodes lancea, was carried out by Aspergillus niger and Aspergillus cellulosae IFO 4040. Compound 1 was easily converted to compounds 2-9 by A. niger, and compounds 10 and 11 by A. cellulosae, respectively. Their stereostructures were established by a combination of high-resolution NMR spectral analysis, X-ray crystallographic analysis, and chemical reactions such as epoxydation.

Developmental patterns of heart rate in altricial avian embryos and hatchlings

The aims of this study were to determine the patterns of development of heart rate (fH) in altricial avian embryos and hatchlings, and then to examine how fH is regulated to meet metabolic requirements in altricial embryos. Embryonic mean heart rate (fH-) in 12 altricial species (Passeriformes and Psittaciformes) increased during pre-pipping incubation in all species except the cockatiel (Nymphicus hollandicus), in which fH- tended to decrease prior to pipping. The rate of increase in fH- tripled during the pipping phase in all species, and fH- was significantly higher during the pipping period and in hatchlings than during pre-pipping development. The O2 pulse (O2 consumed per cardiac beat) of altricial embryos increased in direct proportion to embryo mass (loge/loge base), although fH- was often low prior to pipping, implying that stroke volume increases in the second half of incubation. We conclude that fH contributes more than other factors towards supplying the metabolic demands of the embryo during the middle of incubation and the final pipping phase, but less during the intervening period of late incubation.

Changes in islet capillary angioarchitecture coincide with impaired B-cell function but not with insulin resistance in male Otsuka-Long-Evans-Tokushima fatty rats: dimorphism of the diabetic phenotype at an advanced age.

The Otsuka-Long-Evans-Tokushima fatty (OLETF) rat is a genetic model of spontaneous development of non-insulin-dependent diabetes mellitus (NIDDM) established as an inbred strain after 20 generations of selective breeding. Although they are thought to be genetically homogeneous, they show a dimorphism regarding the diabetic phenotype at an advanced age, with one remaining obese and modestly diabetic while the other becomes lean and overtly diabetic. To clarify the causes for this divergence, we examined the physical, biochemical, and histopathological features in rats at 50 weeks of age, including an analysis of islet angioarchitecture. Sixty-one of 85 male OLETF rats lost weight, while the remainder remained obese. Mean nonfasting plasma glucose in the lean group was 21.8+/-4.6 mmol/L, significantly higher versus the obese group (10.5+/-1.4 mmol/L) and the age-matched control Long-Evans-Tokushima-Otsuka (LETO) group (7.1+/-0.6 mmol/L). Morphological studies of the pancreas from the lean group showed enlarged multilobulated fibrotic islets with a paucity of B cells, whereas islets from the obese group appeared slightly enlarged and showed a relative abundance of B cells. The fine capillaries that form a network in the islets were extremely sparse in the lean group, resulting in a defective glomerular-like configuration, whereas those from the obese group were dense, forming a nearly typical glomerular-like configuration. Increased plasma insulin responses to oral and intravenous (i.v.) glucose and i.v. glucagon loads were nearly absent in the lean group, while they were evident in the obese group, although to a lesser extent compared with the LETO group. Mean insulin secretory output from the perfused pancreas in response to 11.1 mmol/L glucose in the lean group (3.5+/-2.2 pmol/20 min) was significantly lower versus the obese group (8.8+/-6.5 pmol/20 min) and LETO group (22.0+/-10.8 pmol/20 min). Similarly, pancreatic insulin content was significantly lower in the lean group (9.3+/-6.1 microg) versus the others (26.1+/-17.3 microg for obese and 41.1+/-24.8 microg for LETO). In vivo insulin-stimulated glucose uptake measured by a euglycemic clamp technique was significantly higher in the lean group compared with the obese group. These results demonstrate that the dimorphism regarding the diabetic phenotype in male OLETF rats at 50 weeks of age was due to differences in the number of islet B cells, which could be the result of a variation in the capacity for B-cell proliferation among male OLETF rats.