Biomedical subjects

X M Yang

Publications and source records attributed to X M Yang.

At least 19 recordsLinked to original sources

PubMed2026

[Intestinal microbiota alterations after digestive tract reconstruction surgery and their impacts on host physiology].

The gut microbiota, acknowledged as the human body's 'second genome', plays a pivotal role in maintaining health. Digestive tract reconstruction surgery profoundly alters the anatomical structure and physiological environment of the gastrointestinal tract, thereby inducing significant shifts in the intestinal microbiota. These microbial changes subsequently influence host physiological functions through metabolic, immune, neuroendocrine, and other pathways. For instance, Roux-en-Y gastric bypass surgery enriches short-chain fatty acid(SCFA)-producing Bacteroides, improving systemic insulin sensitivity. Conversely, pancreaticoduodenectomy leads to a marked enrichment of potential pathobionts such as Klebsiella and Clostridium, which may elevate the risk of infections and tumor recurrence. This review comprehensively summarizes the characteristic changes in the gut microbiota following various digestive tract reconstruction procedures and discusses their multifaceted impacts on host physiology, aiming to provide insights for future experimental research and clinical practice.

Humans↗

PubMed2005

Attention to the hiding iodine deficiency in pregnant and lactating women after universal salt iodization: A multi-community study in China.

BACKGROUND: Monitoring of iodine nutrition depends chiefly on the urinary iodine concentration in representative samples from the population. International groups have recommended school-age children as a convenient group for surveys, because of their accessibility and young age, but the relevance of this group to others, especially pregnant women, is not well established. OBJECTIVE: The purpose was to compare different approaches to assessing iodine nutrition within communities, especially for pregnant and lactating women. DESIGN: In an urban and a rural site from each of the 11 Chinese provinces, covering a wide geographic and socioeconomic range, we measured the iodine content of household salt and drinking water, the thyroid volume in school children, and the urinary iodine concentration in five population subsets; in some sites we also assessed iodine in breast milk and thyroid size in adult women. RESULTS: The median urinary iodine concentrations for pregnant and lactating women were well below those of the schoolchildren from the same community in most study sites, the difference between medians, at overall level, being about 50 microg/l for the pregnant and 40 microg/l for the lactating, respectively. When ranked by median urinary iodine concentrations at overall level, the order of the groups was: all infants, schoolchildren, women of childbearing age, lactating women and pregnant women in both urban and rural sites. This relative distribution was constant among the study sites. From it, we derived a relationship to predict the median values for other groups, based on the data of schoolchildren. The median iodine content of salt was 30.9 ppm in urban sites and 31.3 ppm in rural sites, respectively, close to the nationally mandated 35 mg/kg. Water had low iodine content (3.7 microg/l) in both urban and rural sites except in a rural site from Tianjin. Ultrasonography showed that 6.5% of 1329 children in urban sites and 5.3% of 1431 children in rural sites had thyroid enlargement. Breast milk had a median iodine content of 135.9 microg/l in the urban and 157.5 microg/l in the rural. The goiter prevalence by palpation was low (2.0%) among all women examined (3367), but higher in pregnant women (2.7%) than in lactating women or other adult women. CONCLUSIONS: An effective iodized salt program has brought iodine sufficiency to most of China, but pregnant women in some areas may still risk deficiency and need further supplements. We suggest other countries and international agencies pay more attention to pregnancy, where iodine deficiency has its worst consequences.

Adult↗

PubMed2004

EDAG regulates the proliferation and differentiation of hematopoietic cells and resists cell apoptosis through the activation of nuclear factor-kappa B.

Erythroid differentiation-associated gene (EDAG) is considered to be a human hematopoiesis-specific gene. Here, we reported that downregulation of EDAG protein in K562 cells resulted in inhibition of growth and colony formation, and enhancement of sensitivity to erythroid differentiation induced by hemin. Overexpression of EDAG in HL-60 cells significantly blocked the expression of the monocyte/macrophage differentiation marker CD11b after pentahydroxytiglia myristate acetate induction. Moreover, overexpression of EDAG in pro-B Ba/F3 cells prolonged survival and increased the expression of c-Myc, Bcl-2 and Bcl-xL in the absence of interleukin-3 (IL-3). Furthermore, we showed that EDAG enhanced the transcriptional activity of nuclear factor-kappa B (NF-kappa B), and high DNA-binding activity of NF-kappa B was sustained in Ba/F3 EDAG cells after IL-3 was withdrawn. Inhibition of NF-kappa B activity resulted in promoting Ba/F3 EDAG cells death. These results suggest that EDAG regulates the proliferation and differentiation of hematopoietic cells and resists cell apoptosis through the activation of NF-kappa B.

Apoptosis↗

PubMed2003

A subpopulation of dorsal raphe nucleus neurons retrogradely labeled with cholera toxin-B injected into the inner ear.

Previous studies have shown that: (1) raphe neurons respond to acoustic and vestibular stimuli, some with a latency of 10-15 ms; (2) alterations of the raphe nuclei alter the acoustic startle reflex; (3) the dorsal raphe nucleus (DRN) is the major source of serotonergic neurons; and (4) approximately 57% of the DRN neurons are nonserotonergic. In the present study, cholera toxin subunit-B (CTB) was injected into cat cochleas, and the brain tissue was examined after a survival period of 5-7 days. Aside from neurons which were known to project to the inner ear, i.e., olivocochlear and vestibular efferent neurons, a surprising new finding was made that somata of a subpopulation of DRN neurons were intensely labeled with CTB. These CTB-labeled neurons were densely distributed in a dorsomedian part of the DRN with some in a surrounding area outside the DRN. The present results suggest that a novel raphe-labyrinthine projection may exist. A future study of anterograde labeling with injections of a tracer in the DRN will be needed to establish the existence of a raphe-labyrinthine projection more thoroughly. A raphe-labyrinthine descending input, together with an ascending input from the inner ear to the DRN through intervening neurons, such as the juxta-acousticofloccular raphe neurons (JAFRNs) described by Ye and Kim, may mediate a brain stem reflex whereby a salient multisensory (including auditory and vestibular) stimulus may alter the sensitivity of the inner ear. As a mammal responds to a biologically important auditory-vestibular multisensory event, the raphe projections to the inner ear and other auditory and vestibular structures may enhance the mammal's ability to localize and recognize the sound and respond properly. The raphe-labyrinthine projection may also modulate the inner ear's sensitivity as a function of the sleep-wake arousal state of an organism on a slower time course.

Animals↗

PubMed2003

Long-term effects of fertilization on soil organic carbon changes in continuous corn of northeast China: RothC model simulations.

Soil organic C (SOC) content can increase by managing land use practices in which the rates of organic C input exceed those of organic C mineralization. Understanding the changes in SOC content of Black soils (mainly Typic Halpudoll) in northeast China is necessary for sustainable using of soil resources there. We used the RothC model to estimate SOC levels of Black soils under monoculture cropping corn in a long-term fertilization trial at Gongzhuling, Jilin Province, China. The model outputs for the changes in SOC were compared with measured data in this long-term fertilization/manure trial. The sound performance of model in simulating SOC changes suggests that RothC is feasible with Black soils in the temperate climatic region of northeast China. The modeled and measured results indicated that the treatment without fertilizer/farmyard manure (FYM) addition led to a continuous decline in SOC during the study period and N and NPK fertilization were inadequate to maintain the SOC levels in the plow layer (upper 20 cm) unless FYM was added under the current conventional management associated with no above-ground crop residues returning into the soil. Soil organic carbon could follow the same path of decline if the same management practices are maintained. Model results indicate that returning above-ground crop residues to the soil from 2002 to 2022 would increase SOC by 26% for the treatment without fertilization addition, 40% for N treatment, 45% for NPK treatment, and 38% and 46% for N and NPK treatments with FYM addition, compared to the levels in the corresponding treatments in 2002. The simulation results suggest that the RothC model is a feasible tool to assess SOC trend under different management practices, and returning above-ground crop residues into the soil would lead to a remarkable increase in SOC of Black soils in the region.

Agriculture↗

PubMed2001

Acetylcholine, bradykinin, opioids, and phenylephrine, but not adenosine, trigger preconditioning by generating free radicals and opening mitochondrial K(ATP) channels.

It has been assumed that all G(i)-coupled receptors trigger the protective action of preconditioning by means of an identical intracellular signaling pathway. To test this assumption, rabbit hearts were isolated and perfused with Krebs buffer. All hearts were subjected to a 30-minute coronary artery occlusion followed by 120 minutes of reperfusion. Risk area was measured with fluorescent particles and infarct size with triphenyltetrazolium chloride staining. Control hearts showed 29.1+/-2.8% infarction of the risk zone. A 5-minute infusion of acetylcholine (0.55 mmol/L) beginning 15 minutes before the 30-minute occlusion resulted in significant protection (9.2+/-2.7% infarction). This protection could be blocked by administration of 300 micromol/L N-2-mercaptopropionyl glycine (MPG), a free radical scavenger, or by 200 micromol/L 5-hydroxydecanoate (5-HD), a mitochondrial K(ATP) antagonist, for 15 minutes beginning 5 minutes before the acetylcholine infusion (35.2+/-3.9% and 27.8+/-2.4% infarction, respectively). Similar protection was observed with other known triggers, ie, bradykinin (0.4 micromol/L), morphine (0.3 micromol/L), and phenylephrine (0.1 micromol/L), and in each case protection was completely abrogated by either MPG or 5-HD. In contrast, protection by adenosine or its analog N(6)-(2-phenylisopropyl) adenosine could not be blocked by either MPG or 5-HD. Therefore, whereas most of the tested agonists trigger protection by a pathway that requires opening of mitochondrial K(ATP) channels and production of free radicals, the protective action of adenosine is not dependent on either of these steps. Hence, it cannot be assumed that all G(i)-coupled receptors use the same signal transduction pathways to trigger preconditioning.

Acetylcholine↗

PubMed2001

Acute ethanol exposure fails to elicit preconditioning-like protection in in situ rabbit hearts because of its continued presence during ischemia.

OBJECTIVES: Is the timing of exposure critical for ethanol's ability to induce cardioprotection? BACKGROUND: Acute ethanol exposure has been reported to mimic ischemic preconditioning in vitro, but it failed to protect in situ. We hypothesized that these conflicting findings were related to ethanol's presence during ischemia in situ. METHODS: The effect on infarct size (triphenyltetrazolium chloride) of acute ethanol exposure (0.35, 0.7, and 1.4 g/kg IV) 10 min before ischemia was measured in open-chest rabbits after 30 min of regional ischemia and reperfusion and was compared to ethanol's ability to reduce infarct size in isolated hearts in which the timing of ethanol exposure could be varied. RESULTS: Ethanol exposure in situ shortly before ischemia did not reduce infarct size. Moreover, ethanol abolished protection from both ischemic preconditioning and mitochondrial KATP channel activation. In contrast, in buffer-perfused hearts exposed to 10 to 50 mmol/liter ethanol for 5 min followed by washout before ischemia, infarct size was significantly reduced. When ethanol exposure was prolonged until the end of ischemia in isolated hearts, protection was abolished. Conversely, protection was seen when ethanol was infused in situ followed by removal of the heart and perfusion with ethanol-free buffer prior to ischemia in a Langendorff preparation. When 50 min were allowed to metabolize the ethanol prior to ischemia, protection could also be shown in situ. CONCLUSIONS: Ethanol exposure followed by washout or sufficient time to metabolize the alcohol prior to ischemia induces preconditioning-like myocardial protection. However, if present throughout ischemia, ethanol actually blocks all preconditioning-related protection.

Animals↗

PubMed2001

The H89 cAMP-dependent protein kinase inhibitor blocks Plasmodium falciparum development in infected erythrocytes.

In Plasmodium falciparum, the causative agent of human malaria, the catalytic subunit gene of cAMP-dependent protein kinase (Pfpka-c) exists as a single copy. Interestingly, its expression appears developmentally regulated, being at higher levels in the pathogenic asexual stages than in the sexual forms of parasite that are responsible for transmission to the mosquito vector. Within asexual parasites, PfPKA activity can be readily detected in schizonts. Similar to endogenous PKA activity of noninfected red blood cells, the parasite enzyme can be stimulated by cAMP and inhibited by protein kinase inhibitor.Importantly, ex vivo treatment of infected erythrocytes with the classical PKA-C inhibitor H89 leads to a block in parasite growth. This suggests that the PKA activities of infected red blood cells are essential for parasite multiplication. Finally, structural considerations suggest that drugs targeting the parasite, rather than the erythrocyte enzyme, might be developed that could help in the fight against malaria.

Amino Acid Sequence↗

PubMed2001

Mutation and abnormal expression of the fragile histidine triad gene in nasopharyngeal carcinoma.

OBJECTIVE: To determine alterations of fragile histidine triad (FHIT) gene in nasopharyngeal carcinoma and the correlation of FHIT gene with nasopharyngeal carcinogenesis. STUDY DESIGN: Prospective study. METHODS: A total of 28 nasopharyngeal carcinoma and 16 normal nasopharyngeal epithelium specimens were examined for abnormalities of FHIT gene by nested reverse-transcriptase-polymerase chain reaction and DNA sequencing. RESULTS: The deletion of FHIT gene was not observed in 16 normal nasopharyngeal epithelium specimens. In 28 cases of nasopharyngeal carcinoma tissues, 12 (42.9%) exhibited FHIT aberrant transcripts. Complementary DNA sequencing revealed exonic deletion, small DNA insertion, synonymous mutation in exon 8, or frameshift mutation in exon 5. CONCLUSIONS: The present results suggest that the FHIT gene may play an important role in the pathogenesis of nasopharyngeal carcinoma and may be one of the candidate tumor suppressor genes in nasopharyngeal carcinoma.

Biopsy↗

PubMed2001

Hyperglycemia modulates angiotensinogen gene expression.

Elevated plasma angiotensinogen (AGT) levels have been demonstrated in insulin-resistant states such as obesity and type 2 diabetes mellitus (DM2), conditions that are directly correlated to hypertension. We examined whether hyperinsulinemia or hyperglycemia may modulate fat and liver AGT gene expression and whether obesity and insulin resistance are associated with abnormal AGT regulation. In addition, because the hexosamine biosynthetic pathway is considered to function as a biochemical sensor of intracellular nutrient availability, we hypothesized that activation of this pathway would acutely mediate in vivo the induction of AGT gene expression in fat and liver. We studied chronically catheterized lean (approximately 300 g) and obese (approximately 450 g) Sprague-Dawley rats in four clamp studies (n = 3/group), creating physiological hyperinsulinemia (approximately 60 microU/ml, by an insulin clamp), hyperglycemia (approximately 18 mM, by a pancreatic clamp using somatostatin to prevent endogenous insulin secretion), or euglycemia with glucosamine infusion (GlcN; 30 micromol. kg(-1). min(-1)) and equivalent saline infusions (as a control). Although insulin infusion suppressed AGT gene expression in fat and liver of lean rats, the obese rats demonstrated resistance to this effect of insulin. In contrast, hyperglycemia at basal insulin levels activated AGT gene expression in fat and liver by approximately threefold in both lean and obese rats (P < 0.001). Finally, GlcN infusion simulated the effects of hyperglycemia on fat and liver AGT gene expression (2-fold increase, P < 0.001). Our results support the hypothesis that physiological nutrient "pulses" may acutely induce AGT gene expression in both adipose tissue and liver through the activation of the hexosamine biosynthetic pathway. Resistance to the suppressive effect of insulin on AGT expression in obese rats may potentiate the effect of nutrients on AGT gene expression. We propose that increased AGT gene expression and possibly its production may provide another link between obesity/insulin resistance and hypertension.

Adipose Tissue↗

PubMed2001

Physiological increase in plasma leptin markedly inhibits insulin secretion in vivo.

The demonstration of leptin receptors on the pancreatic beta-cells suggests the possibility of direct actions of leptin on insulin secretion. In vitro studies on islets or perfused pancreas and beta-cell lines produced inconsistent results. We performed an in vivo study to distinctly examine whether leptin has an effect on glucose-stimulated insulin secretion. Young chronically catheterized Sprague-Dawley rats (n = 28) were subjected to a 4-h hyperglycemic clamp study (approximately 11 mmol/l). At minute 120 to 240, rats were assigned to receive either saline or leptin (0.1, 0.5, and 5 microg x kg(-1) x min) infusion. Leptin decreased plasma insulin levels abruptly, and an approximately twofold decrease in plasma insulin levels compared with saline control was sustained over the 2 h of the study (14.8 +/- 5.8 vs. 34.8 +/- 2.6 ng/ml with leptin and saline infusion, respectively, P < 0.001). Moreover, a dose-dependent decrease in plasma insulin levels was noted (r = -0.731, P < 0.01). Since milrinone, an inhibitor of cAMP phosphodiesterase (PDE) 3, did not reverse the effect of leptin on glucose-induced insulin secretion, its action may be independent of PDE3. These findings suggest that acute physiological increase in plasma leptin levels acutely and significantly inhibits glucose-stimulated insulin secretion in vivo. The site of leptin effects on insulin secretion remains to be determined.

Animals↗

PubMed2001

Isolation and Characterization of EDAG-1, A Novel Gene Related to Regulation in Hematopoietic System.

A novel gene, named embryonic develop associated gene 1 ( EDAG -1) and abundantly expressed in human fetal liver tissues, was isolated by screening a human fetal liver cDNA library and the 5' RACE. The full length of EDAG-1 mRNA is 2 166 bp, with an open reading frame of 1 452 bp neucleotides, encoding a 484 amino acid protein. No domain or motif was found similar with other genes by Blast program. Two copies of AUUUA motif in 3' non-translated region show instability of its mRNA. The molecular weight of the protein is 55.3 kD identified by the translation in vitro. EDAG-1 is specifically expressed in hematopoietic tissues, and is quickly down-regulated during the differentiation of K562 cells induced by hemin and EPO. These results show that EDAG-1 is related to the regulation in hematopoietic system and the development of leukemia.

Journal Article↗

PubMed2000

Opening of mitochondrial K(ATP) channels triggers the preconditioned state by generating free radicals.

The critical time for opening mitochondrial (mito) K(ATP) channels, putative end effectors of ischemic preconditioning (PC), was examined. In isolated rabbit hearts 29+/-3% of risk zone infarcted after 30 minutes of regional ischemia. Ischemic PC or 5-minute exposure to 10 micromol/L diazoxide, a mito K(ATP) channel opener, reduced infarction to 3+/-1% and 8+/-1%, respectively. The mito K(ATP) channel closer 5-hydroxydecanoate (200 micromol/L), bracketing either 5-minute PC ischemia or diazoxide infusion, blocked protection (24+/-3 and 28+/-6% infarction, respectively). However, 5-hydroxydecanoate starting 5 minutes before long ischemia did not affect protection. Glibenclamide (5 micromol/L), another K(ATP) channel closer, blocked the protection by PC only when administered early. These data suggest that K(ATP) channel opening triggers protection but is not the final step. Five minutes of diazoxide followed by a 30-minute washout still reduced infarct size (8+/-3%), implying memory as seen with other PC triggers. The protection by diazoxide was not blocked by 5 micromol/L chelerythrine, a protein kinase C antagonist, given either to bracket diazoxide infusion or just before the index ischemia. Bracketing preischemic exposure to diazoxide with 50 micromol/L genistein, a tyrosine kinase antagonist, did not affect infarction, but genistein blocked the protection by diazoxide when administered shortly before the index ischemia. Thus, although it is not protein kinase C-dependent, the protection by diazoxide involves tyrosine kinase. Bracketing diazoxide perfusion with N:-(2-mercaptopropionyl) glycine (300 micromol/L) or Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (7 micromol/L), each of which is a free radical scavenger, blocked protection, indicating that diazoxide triggers protection through free radicals. Therefore, mito K(ATP) channels are not the end effectors of protection, but rather their opening before ischemia generates free radicals that trigger entrance into a preconditioned state and activation of kinases.

Adenosine Triphosphate↗

PubMed2000

Interaction between two discontiguous chain segments from the beta-sheet of Escherichia coli thioredoxin suggests an initiation site for folding.

The approach of comparing folding and folding/binding processes is exquisitely poised to narrow down the regions of the sequence that drive protein folding. We have dissected the small single alpha/beta domain of oxidized Escherichia coli thioredoxin (Trx) into three complementary fragments (N, residues 1-37; M, residues 38-73; and C, residues 74-108) to study them in isolation and upon recombination by far-UV CD and NMR spectroscopy. The isolated fragments show a minimum of ellipticity of ca. 197 nm in their far-UV CD spectra without concentration dependence, chemical shifts of H(alpha) that are close to the random coil values, and no medium- and long-range NOE connectivities in their three-dimensional NMR spectra. These fragments behave as disordered monomers. Only the far-UV CD spectra of binary or ternary mixtures that contain N- and C-fragments are different from the sum of their individual spectra, which is indicative of folding and/or binding of these fragments. Indeed, the cross-peaks corresponding to the rather hydrophobic beta(2) and beta(4) regions of the beta-sheet of Trx disappear from the (1)H-(15)N HSQC spectra of isolated labeled N- and C-fragments, respectively, upon addition of the unlabeled complementary fragments. The disappearing cross-peaks indicate interactions between the beta(2) and beta(4) regions, and their reappearance at lower temperatures indicates unfolding and/or dissociation of heteromers that are predominantly held by hydrophobic forces. Our results argue that the folding of Trx begins by zippering two discontiguous and rather hydrophobic chain segments (beta(2) and beta(4)) corresponding to neighboring strands of the native beta-sheet.

Circular Dichroism↗

PubMed2000

Favorable remodeling enhances recovery of regional myocardial function in the weeks after infarction in ischemically preconditioned hearts.

BACKGROUND: In a previous study, we found that recovery of segment shortening in the ischemic zone of conscious, chronically instrumented rabbits was significantly better in ischemically preconditioned than control animals after 72 hours of reperfusion. However, although this period of reperfusion was felt to be sufficient to allow recovery from stunning, regional function was disproportionately low for the size of the infarcts. METHODS AND RESULTS: To further characterize the recovery of left ventricular regional function, rabbits were chronically instrumented with a balloon occluder around a branch of the left coronary artery and a pair of ultrasonic crystals to monitor segment shortening in the ischemic zone. The preconditioned group had 1 cycle of 5-minute occlusion/10-minute reperfusion before a 30-minute occlusion, whereas control rabbits experienced only the 30-minute occlusion. All monitored segments were either dyskinetic or akinetic during the 30-minute occlusion. There was no difference in function between the 2 groups until 24 hours of reperfusion. At 72 hours, systolic shortening in control hearts averaged only 5% of the preischemic value, whereas shortening was 29% of baseline in preconditioned hearts. By day 21, systolic shortening averaged 26% in control hearts and 65% in preconditioned hearts (P<0.02) and appeared to have reached a plateau. Infarct size was 31.4+/-2.8% and 15.5+/-2.1% in control and preconditioned hearts, respectively. Moreover, in ischemically preconditioned hearts, the recovery of regional function was better than in controls for any given amount of microinfarction in the myocardial segment between crystals (P=0.02). CONCLUSIONS: The progressive improvement in preconditioned hearts is most consistent with favorable remodeling in the ischemic zone, which the preconditioning process seems to accentuate.

Animals↗

PubMed2000

Partitioning of the 2-microm circle plasmid of Saccharomyces cerevisiae. Functional coordination with chromosome segregation and plasmid-encoded rep protein distribution.

The efficient partitioning of the 2-microm plasmid of Saccharomyces cerevisiae at cell division is dependent on two plasmid-encoded proteins (Rep1p and Rep2p), together with the cis-acting locus REP3 (STB). In addition, host encoded factors are likely to contribute to plasmid segregation. Direct observation of a 2-microm-derived plasmid in live yeast cells indicates that the multiple plasmid copies are located in the nucleus, predominantly in clusters with characteristic shapes. Comparison to a single-tagged chromosome or to a yeast centromeric plasmid shows that the segregation kinetics of the 2-microm plasmid and the chromosome are quite similar during the yeast cell cycle. Immunofluorescence analysis reveals that the plasmid is colocalized with the Rep1 and Rep2 proteins within the yeast nucleus. Furthermore, the Rep proteins (and therefore the plasmid) tend to concentrate near the poles of the yeast mitotic spindle. Depolymerization of the spindle results in partial dispersion of the Rep proteins in the nucleus concomitant with a loosening in the association between plasmid molecules. In an ipl1-2 yeast strain, shifted to the nonpermissive temperature, the chromosomes and plasmid almost always missegregate in tandem. Our results suggest that, after DNA replication, plasmid distribution to the daughter cells occurs in the form of specific DNA-protein aggregates. They further indicate that the plasmid partitioning mechanism may exploit at least some of the components of the cellular machinery required for chromosomal segregation.

Cell Cycle↗

PubMed2000

Limitation of infarct size in rabbit hearts by the novel adenosine receptor agonist AMP 579 administered at reperfusion.

The novel A(1)/A(2)adenosine receptor agonist AMP 579 has been reported to reduce myocardial infarct size in pig and dog. The present study tested the effect of AMP 579 in two rabbit models. In open-chest rabbits undergoing 30 min of regional ischemia and 3 h of reperfusion AMP 579 (3 microg/min/kg) reduced infarct size when treatment was started either 10 min before ischemia or 10 min prior to reperfusion from 36.4+/-3.1% of the risk zone in untreated hearts to 11.8+/-4.4 and 12.3+/-1.0%, respectively. To determine whether protection observed when the drug was administered shortly before reperfusion represented a long-lasting effect rather than merely a transient delay of necrosis, the chest wound was closed in layers and the rabbits permitted to recover. After 3 days the hearts were removed to evaluate infarct size. Continued limitation of infarct size after 3 days of reperfusion (8.2+/-2.8% of the risk zone) confirmed that sustained tissue salvage had been conferred by the drug. In isolated, buffer-perfused rabbit hearts undergoing 30 min of regional ischemia and 2 h of reperfusion, AMP 579 again limited infarct size (8.6+/-2.9% of the risk zone) when treatment started 10 min prior to reperfusion, arguing against an anti-leukocyte mechanism of protection. AMP 579's protective effect in this in vitro model was abrogated by 8-(p-sulfophenyl)theophylline, indicating that it was mediated through adenosine receptors. We conclude that AMP 579 given just prior to reperfusion may be an effective anti-infarct intervention.

Animals↗

PubMed2000

Phase-specific optimization of multiple endotoxin-protein production with genetically engineered Bacillus thuringiensis.

An optimization approach was designed to specifically study the toxin-expression phase of the fermentation process of a genetically engineered Bacillus thuringiensis strain expressing dual toxin proteins (CryI and CryIII). The study has resulted in the discovery of important nutrient and process factors affecting toxin-protein yield. The results show that the existence of nitrogen sources in the medium during the toxin-expression phase is detrimental to the toxin-protein expression, while a high carbon-source level (40 g/l) encouraged protein expression. The study also suggests that the depletion of nitrogen source is the trigger for B. thuringiensis to initiate sporulation and toxin expression. A temperature setting of 28 degrees C for B. thuringiensis fermentation processes is optimal for protein yield, and reduces the oxygen requirement. It was found that the optimal conditions for spore yield and for toxin-protein yield were not the same, even though sporulation and toxin formation proceed simultaneously during the fermentation process. Scale-up studies were also conducted to confirm the optimal conditions obtained from a small-scale optimization study.

Bacillus thuringiensis↗