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Biomedical subjects

Gang Chen

Publications and source records attributed to Gang Chen.

At least 235 records · Page 13Linked to original sources

Microbial surface thermodynamics and interactions in aqueous media.

Microbial surface thermodynamics and interactions in aqueous media were investigated for seven typical rod-shaped bacterial strains of Enterobacteriaceae, Pseudomonadaceas, and Bacillaceae, which included Escherichia coli HB101, Escherichia coli JM109, Pseudomonas fluorescens, Pseudomonas putida, Pseudomonas aeruginosa, Pseudomonas sp., and Bacillus subtilis. All the microorganisms studied exhibited a monopolar and predominant hydrophilic surface and a negative Delta G132tot, total free energy of interactions between microbes (1) and silica gel or Canadian River Alluvium (CRA) (2) immersed in water (3) at the equilibrium distance, which accounted for their attachment on the medium surface. The microbial attachment was proportional to the corresponding Delta G132tot values. Among the microorganisms studied, B. subtilis had the most attachment on both silica gel and CRA because it had the smallest Delta G132tot values (-17.14kT for silica gel and -21.84kT for CRA). The origins of Lifshitz-van der Waals, Lewis acid/base, and electrostatic interactions were discussed and related to experimental observations.

Bacillus subtilis↗

Monotherapy with LF 15-0195, an analogue of 15-deoxyspergualin, significantly prolongs renal allograft survival in monkeys.

BACKGROUND: LF 15-0195 is a novel, more potent, and less toxic analogue of 15-deoxyspergualin, an antibiotic used as an immunosuppressive agent to prevent rejection of organ transplants. This study was undertaken to determine whether LF 15-0195 monotherapy would prevent renal allograft rejection in a nonhuman primate model. METHODS: In the study groups, recipients received LF 15-0195 monotherapy at doses of 0.065 mg/kg per day (group 2, n=4), 0.13 mg/kg per day (group 3, n=4), or 0.2 mg/kg per day (group 4, n=4), administered subcutaneously, on postoperative days 0 to 14. RESULTS: Group 1 consisted of untreated control recipients, all of which developed advanced graft rejection after surviving for an average of 6.5+/-0.6 days. LF 15-0195 treatment significantly prolonged graft survival in groups 2, 3, and 4, to 20+/-20 days, 49+/-5 days, and 39+/-4 days, respectively. Animals in groups 3 and 4 demonstrated no evidence of rejection during LF 15-0195 treatments. The animals maintained stable renal function for 2 weeks after LF 15-0195 withdrawal but gradually developed rejection at 5 to 6 weeks. Pathologic studies demonstrated that vascular graft rejection was attenuated in LF 15-0195-treated allografts, compared with control specimens. These groups also demonstrated transient reductions in lymphocyte counts during treatment, which returned to normal levels 2 weeks after LF 15-0195 withdrawal. Total serum concentrations of IgM and IgG decreased by a mean of 20.4% and a mean of 31.4%, respectively, at the end of LF 15-0195 treatment (postoperative day 14). LF 15-0195 did not significantly alter thrombocyte counts or hemoglobin levels. Necropsy studies showed no evidence of drug toxicity in the heart, liver, spleen, intestines, stomach, or colon. CONCLUSIONS: LF 15-0195 monotherapy significantly prolonged renal allograft survival in monkeys. These encouraging data suggest that this novel agent may be of future value in clinical transplantation.

Animals↗

Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix.

The structure of human BCL-w, an anti-apoptotic member of the BCL-2 family, was determined by triple-resonance NMR spectroscopy and molecular modeling. Introduction of a single amino acid substitution (P117V) significantly improved the quality of the NMR spectra obtained. The cytosolic domain of BCL-w consists of 8 alpha-helices, which adopt a fold similar to that of BCL-xL, BCL-2, and BAX proteins. Pairwise root meant square deviation values were less than 3 A for backbone atoms of structurally equivalent regions. Interestingly, the C-terminal helix alpha8 of BCL-w folds into the BH3-binding hydrophobic cleft of the protein, in a fashion similar to the C-terminal transmembrane helix of BAX. A peptide corresponding to the BH3 region of the pro-apoptotic protein, BID, could displace helix alpha8 from the BCL-w cleft, resulting in helix unfolding. Deletion of helix alpha8 increased binding affinities of BCL-w for BAK and BID BH3-peptides, indicating that this helix competes for peptide binding to the hydrophobic cleft. These results suggest that although the cytosolic domain of BCL-w exhibits an overall structure similar to that of BCL-xL and BCL-2, the unique organization of its C-terminal helix may modulate BCL-w interactions with pro-apoptotic binding partners.

Amino Acid Sequence↗

Optical imaging of long-term depression in the mouse cerebellar cortex in vivo.

Conjunctive stimulation of climbing fiber and parallel fiber inputs results in long-term depression (LTD) at parallel fiber-Purkinje cell synapses. Although hypothesized to play a major role in cerebellar motor learning, there has been no characterization of the cellular and molecular mechanisms of LTD in the whole animal, let alone its spatial properties, both of which are critical to understanding the role of LTD in cerebellar function. Neutral red optical imaging of the cerebellar cortex in the anesthetized mouse was used to visualize the spatial patterns of activation. Stimulation of the parallel fibers evoked a transverse beam of optical activity, and stimulation of the contralateral inferior olive evoked parasagittal bands. Conjunctive stimulation of parallel fibers and climbing fibers induced a long-term decrease (at least 1 hr) in the optical response to subsequent parallel fiber activation confined to the region of interaction between these two inputs. Activation of climbing fibers alone failed to induce the long-term decrease. Field potential recordings confirmed that the depression is postsynaptic and restricted to the interaction site. The long-term depression in the beam was prevented by a group 1 metabotropic glutamate receptor (mGluR(1)) antagonist and was absent in transgenic mice selectively expressing an inhibitor of protein kinase C (PKC) in Purkinje cells. Conversely, the long-term depression occurred in the mGluR(4) knock-out mouse, consistent with its postsynaptic origin. In addition to providing the first visualization of parallel fiber-Purkinje cell LTD in the cerebellar cortex, this study demonstrates the spatial specificity of LTD and its dependence on mGluR(1) and PKC in vivo.

Animals↗

Oxidation of carbon nanotubes by singlet O2.

Chemisorption of singlet (1)Delta(g) O2 on single-walled carbon nanotubes is reexamined by first principles calculations, and the reaction barrier is substantially lower than previously reported when the spin on O2 is correctly treated. The process is initiated by the cycloaddition of a singlet O2 on top of a C-C bond and ended with an epoxy structure with each of the two oxygen atoms occupying a bridge position. The overall process is exothermic, with an activation barrier as low as 0.61 eV for the (8, 0) tube. Our results raise the possibility that carbon nanotubes with small diameters could be degraded after exposure to air and sunlight, similar to the degradation of natural rubber and synthetic plastics.

Journal Article↗

Microchip capillary electrophoresis coupled with a boron-doped diamond electrode-based electrochemical detector.

The attractive behavior and advantages of a diamond electrode detector for a micromachined capillary electrophoresis (CE) system are discussed. A chemically vapor-deposited boron-doped diamond (BDD) film band (0.3 x 6.0 mm) electrode is used for end-column amperomettic detection. The favorable performance of the diamond electrode microchip detector is indicated from comparison to a commonly used thick-film carbon detector. The diamond electrode offers enhanced sensitivity, lower noise levels, and sharper peaks for several groups of important anaytes (nitroaromatic explosives, organophosphate nerve agents, phenols). The favorable signal-to-background characteristics of the BDD-based CE detector are coupled with a greatly improved resistance to surface fouling and greater isolation from high separation voltages. The enhanced stability is indicated from a RSD of 0.8% for 60 repetitive measurements of 5 ppm 2,4,6-trinitrotoluene (vs RSD of 10.8% at the thick-film carbon electrode). A highly linear response is obtained for the explosives 1,3-dinitrobenzene and 2,4-dinitrotoluene over the 200-1,400 ppb range, with detection limits of 70 and 110 ppb, respectively. Factors influencing the performance of the BDD detector are assessed and optimized. The attractive properties of BDD make it very promising material for electrochemical detection in CE microchip systems and other micromachined flow analyzers.

Air Pollutants, Occupational↗

Design and analysis of non-inferiority mortality trials in oncology.

The recent revision of the Declaration of Helsinki and the existence of many new therapies that affect survival or serious morbidity, and that therefore cannot be denied patients, have generated increased interest in active-control trials, particularly those intended to show equivalence or non-inferiority to the active-control. A non-inferiority hypothesis has historically been formulated in terms of a fixed margin. This margin was historically designed to exclude a 'clinically meaningful difference', but has become recognized that the margin must also be no larger than the assured effect of the control in the new study. Depending on how this 'assured effect' is determined or estimated, the selected margin may be very small, leading to very large sample sizes, especially when there is an added requirement that a loss of some specified fraction of the assured effect must be ruled out. In cases where it is appropriate, this paper proposes non-inferiority analyses that do not involve a fixed margin, but can be described as a two confidence interval procedure that compares the 95 per cent two-sided CI for the difference between the treatment and the control to a confidence interval for the control effect (based on a meta-analysis of historical data comparing the control to placebo) that is chosen to preserve a study-wide type I error rate of about 0.025 (similar to the usual standard for a superiority trial) for testing for retention of a prespecified fraction of the control effect. The approach assumes that the estimate of the historical active-control effect size is applicable in the current study. If there is reason to believe that this effect size is diminished (for example, improved concomitant therapies) the estimate of this historical effect could be reduced appropriately. The statistical methodology for testing this non-inferiority hypothesis is developed for a hazard ratio (rather than an absolute difference between treatments, because a hazard ratio seems likely to be less population dependent than the absolute difference). In the case of oncology, the hazard ratio is the usual way of comparing treatments with respect to time to event (time to progression or survival) endpoints. The proportional hazards assumption is regarded as reasonable (approximately holding). The testing procedures proposed are conditionally equivalent to two confidence interval procedures that relax the conservatism of two 95 per cent confidence interval testing procedures and preserve the type I error rate at a one-sided 0.025 level. An application of this methodology to Xeloda, a recently approved drug for the treatment of metastatic colorectal cancers, is illustrated. Other methodologies are also described and assessed - including a point estimate procedure, a Bayesian procedure and two delta-method confidence interval procedures. Published in 2003 by John Wiley & Sons, Ltd.

Antimetabolites, Antineoplastic↗

Electrophoretic microchip with dual-opposite injection for simultaneous measurements of anions and cations.

A novel dual-injection poly(methylmethacrylate) (PMMA) microchip electrophoretic system has been designed and fabricated for simultaneous measurements of anions and cations using a single channel and detection device. It consists of two sample reservoirs, on both sides of a common separation channel. Anions and cations can be simultaneously electrokinetically injected into both ends of the separation channel. Due to lower electroosmotic flow in polymer channels compared to glass ones, the cations and anions migrate in opposite directions and can be separated from each other and detected using a movable contactless conductivity detector (MCCD) positioned around the center of the separation channel. The effects of the detector position and of the separation voltage on the response and resolution have been studied and optimized for simultaneous determination of six low-energy explosive-related ions, including ammonium, methyl ammonium, sodium, chloride, nitrate, and perchlorate in a single analytical run (of ca. 3 min). Simultaneous detection of nerve-agent degradation products along with explosive-related anions and cations is also demonstrated. The versatile system can also be used for separately measuring anions or cations. The attractive behavior of the dual-opposite injection microchip offers great promise for a wide range of applications, including "total ion analysis" of various samples.

Anions↗

Reduced gap junctional intercellular communication and altered biological effects in mouse osteoblast and rat liver oval cell lines transfected with dominant-negative connexin 43.

Gap junctional intercellular communication (GJIC) maintains normal growth and differentiation of cells in a tissue. The intercellular molecules traversing gap junctions are largely unknown, but the molecular weight (MW) cutoff is normally 1200 Da. No differences in dye transfer were observed in normal or vector controls of WB-F344 rat liver epithelial or mouse osteoblastic MC3T3-E1 cells with either Lucifer Yellow (LY) with a MW of 457 Da (LY-457) or LY with a MW of 649 Da (LY-649). Transfection of a dominant negative-connexin 43 (Cx43) gene decreased GJIC (>50%) when LY-649 was used, however, normal GJIC was observed in both cell lines when LY-457 was used. Therefore, the MW cut off in these clones was considerably less than the wild type. The dominant negative clones of the MC3T3-E1 cells exhibited over 90% less alkaline phosphatase (ALPase) activity and calcium deposition after the induction of differentiation. Similarly, dominant negative Cx43 inhibited gene expression of ALPase and bone sialoprotein but not osteocalcin in MC3T3-E1. WB-F344 cells normally exhibit a biphasic response to 12-O-tetradecanoylphorbol-13-acetate (TPA) where inhibition of GJIC recovers after 2 h, but the dominant negative clones showed no recovery from inhibition of GJIC by TPA. Dominant negative Cx43 also inhibited the formation of network-like structures by WB-F344 cells on Matrigel. These results demonstrate that the dominant negative gene transfected into cell types containing the wild-type connexins result in diminished channel sizes, thus allowing the determination of whether distinct biological endpoints, i.e., differentiation, are dependent upon either small or high MW intercellular signals.

Animals↗

Food handling behaviors of special importance for pregnant women, infants and young children, the elderly, and immune-compromised people.

This study used a Web-based Delphi process with a group of nationally recognized food safety experts to identify food-handling behaviors of special importance in reducing the risk of foodborne illness among pregnant women, infants and young children, elderly people, and people with compromised immune systems because of disease or pharmacologic therapy. Behaviors were related to 13 pathogens. Top-rated behaviors for pregnant women were associated with Listeria monocytogenes, Toxoplasma gondii, and Salmonella species. Top-rated behaviors for infants and young children, elderly people, and immune-compromised people were associated with a number of different pathogens. The results should help dietetics professionals and community health educators focus their efforts on those behaviors of special importance to the population being targeted.

Age Factors↗

Prolonged cardiac xenograft survival in guinea pig-to-rat model by a highly active cobra venom factor.

A highly active cobra venom factor (CVF) was isolated from the venom of Naja kaouthia by sequential column chromatography. It displays strong anticomplementary activity, and has 1515 U of anticomplementary activity per mg protein. A single dose of 0.1 mg/kg CVF given i.v. to rats completely abrogated complement activity for nearly 5 days. Given 0.02 mg/kg of CVF, the complement activity of rats was reduced by more than 96.5% in 6 h. In guinea pig-to-rat heart transplant model, rats treated with a single dose of 0.05 mg/kg CVF had significantly prolonged xenograft survival (56.12+/-6.27 h in CVF-treated rats vs. 0.19+/-0.07 h in control rats, P<0.001).

Animals↗

Equilibrium and kinetic adsorption of bacteria on alluvial sand and surface thermodynamic interpretation.

Equilibrium and kinetic adsorption of Escherichia coli HB 101, E. coli JM 109, Pseudomonas fluorescens, Pseudomonas putida and Pseudomonas sp. on alluvial sand from the Canadian River alluvium (Norman, OK) was investigated through column experiments. Equilibrium adsorption of these five bacterial strains followed the Freundlich expression and was a function of zero energy points, an indication of the zero energy buffer zone. Among the microorganisms studied, P. putida had the greatest equilibrium adsorption (162.4 x 10(8) cell/g sediment with a microbial injectate concentration of 10(8) cell/ml), followed by Pseudomonas sp. (127.9 x 10(8) cell/g sediment), E. coli HB 101 (62.8 x 10(8) cell/g sediment), E. coli JM 109 (58.4 x 10(8) cell/g sediment), and P. fluorescens (42.6 x 10(8) cell/g sediment). The first-order kinetic adsorption rate coefficient was an exponential function of the total interaction free energy between the bacteria and sediment evaluated at the primary minimum, Delta G(132)(TOT) (PM). E. coli HB 101 had the greatest kinetic adsorption rate coefficient on the sediment (5.10 h(-1)), followed by E. coli JM 109 (4.52 h(-1)), P. fluorescens (2.12 h(-1)), P. putida (2.04 h(-1)), and Pseudomonas sp. (1.34 h(-1)).

Escherichia coli↗

Microbial surface thermodynamics and applications.

Microbial surface thermodynamics is the reflection of microbial physicochemical and biological characteristics and it bridges micro-scale structures with macro-scale biological functions. Microbial surface thermodynamics is theoretically based on colloid surface thermodynamics using the classical theory of colloidal stability, Derjauin-Landau-Verwey-Overbeek (DLVO) theory. An extended DLVO theory is applied to for the hydration forces not considered in the classical DLVO theory. Herein, a review of current application of microbial surface thermodynamic theory is presented. Microbial surface thermodynamic theory is the fundamental theory in interpreting microbial hydrophilicity or hydrophobicity, microbial attachment, and microbial biofilm development.

Bacteria↗

Clinically applicable thermal preconditioning attenuates leukocyte-endothelial interactions.

BACKGROUND: We have previously demonstrated that clinically applicable thermal preconditioning induces heat shock protein 72 (HSP72) and protects against a subsequent ischemia-reperfusion (I/R) injury in an animal model. A core component of I/R injuries is the interaction between activated leukocytes and endothelial cells. We hypothesized that the effects of clinically applicable thermal preconditioning are mediated through attenuation of this leukocyte-endothelial (L-E) interaction. STUDY DESIGN: Twenty-one male Sprague Dawley rats were divided into control, I/R, and preconditioning plus I/R groups. Preconditioning was done under general anesthesia and the animals' temperature raised by 1 degrees C for 15 minutes in a water bath. This was repeated once a day for 5 successive days. I/R injury was caused by occlusion of the superior mesenteric artery for 10 minutes followed by 1 hour of reperfusion. L-E interactions were analyzed using intravital microscopy of a mesenteric vessel in vivo. L-E interactions were determined using leukocyte velocity (which decreases as cells interact), and number of adherent and migrated leukocytes. HSP72 was assessed by Western blot. RESULTS: Ischemia-reperfusion caused a decrease in leukocyte rolling velocity at all timepoints (p < 0.05 versus controls). Preconditioning attenuated the effects of I/R, and leukocyte rolling velocity was significantly improved versus I/R (p < 0.05) to levels similar to those in controls. Similarly, the number of adherent and migrating leukocytes increased significantly (p < 0.05) after I/R versus control at all time points, and preconditioning attenuated these to control levels, (p < 0.05 versus I/R) at both the 30- and 60-minute postischemia time points. Upregulation of HSP72 was demonstrated on Western blot. CONCLUSIONS: These results demonstrate that the benefit of clinically applicable thermal preconditioning is at least partially because of an immunomodulatory role in attenuating leukocyte-endothelial interactions associated with an increased expression of HSP 72.

Analysis of Variance↗

Spontaneous clearance of high-titer serum HBV DNA and risk of hepatocellular carcinoma in a Chinese population.

Chronic hepatitis B virus (HBV) carriers with high-titer viremia (>10(5) virions/ml) are at increased risk for hepatocellular carcinoma (HCC). The aim of this study was to determine the relationship between clearance of high-titer viremia and subsequent risk of HCC. The study population was a prospective cohort of 114 adults from Haimen City, China, all HBV DNA(+) at study entry and followed for 797.8 person-years in total. During follow-up, 54 (47.4%) subjects spontaneously cleared high-titer viremia at least once. Of these, 27 were considered to have undergone stable seroconversion, 16 were considered unstable (12 reversions to HBV DNA positivity and 4 multiple clearances), and 11 did not have sufficient follow-up to determine stability. Of the 114 persons, 26 (22.8%) died during follow-up, 21 (18.4%) from HCC. Using Cox proportional hazards models, the RR of HCC death associated with seroconversion was 2.8 (95% CI = 1.1-7.4), controlling for age, sex, family HCC history, history of acute hepatitis, alcohol use and cigarette smoking. In conclusion, fluctuations of high-titer viremia may indicate increased hepatocellular damage and at least short-term increases in HCC risk. Long-term longitudinal studies are needed to clarify this relationship and its potential usefulness as a prognostic marker in chronic HBV infection.

Adult↗

Pharmacological induction of HSP27 attenuates intimal hyperplasia in vivo.

OBJECTIVES: intimal hyperplasia (IH) is a major cause of re-stenosis post-vascular intervention. Induction of heat shock proteins (HSPs), by thermal pre-conditioning, reduces IH. Our aim was to investigate the effect of the pharmacological HSP inducer herbimycin A on IH in the rat carotid balloon injury model. MATERIALS AND METHODS: thirty male Sprague-Dawley rats were randomized into three groups. All groups underwent balloon injury to the left carotid artery. Stress proteins were induced 18 h pre-operatively by heat shock or herbimycin A. Two weeks post-operatively, animals were sacrificed and carotid intima/media area ratio (I/M ratio) calculated using computerized planimetry. Neo-intimal proliferation was assessed immunohistochemically with PCNA (proliferating cell nuclear antigen). Western blot and immunohistochemistry for arterial HSP70 and HSP27 were performed. RESULTS: heat stress and herbimycin significantly reduced the I/M ratio (p < 0.05 vs balloon injury alone). Neo-intimal proliferation was significantly reduced in the heat stress and herbimycin groups (p < 0.05 vs balloon injury alone). Heat stress induced arterial HSP70 and HSP27. Herbimycin A increased arterial HSP27. CONCLUSION: herbimycin A significantly attenuates IH after balloon injury. HSP27 may be the HSP involved in mediating this response. Pharmacological inducers of HSPs may have a therapeutic role to play in preventing re-stenosis post-vascular intervention.

Angioplasty, Balloon↗

Spreading acidification and depression in the cerebellar cortex.

Optical imaging of activity-dependent pH changes using neutral red has revealed a novel form of propagated activity in the cerebellar cortex: spreading acidification and depression (SAD). Evoked by surface stimulation, SAD is characterized by a propagation geometry that reflects the parasagittal architecture of the cerebellum, high speed of propagation across several folia, and a transient depression of the molecular layer circuitry. The properties of SAD differentiate it from other forms of propagating activity in the nervous system including spreading depression and Ca++ waves. Involving several factors, SAD is hypothesized to be a regenerative process that requires a functioning parallel fibers-Purkinje cell circuit, glutamatergic neurotransmission, and is initiated by increased neuronal excitability. Three possible neuronal and glia substrates in the cerebellar cortex could account for the propagation geometry of SAD. Recently, the authors demonstrated that blocking voltage-gated Kv1.1 potassium channels plays a major role in the generation of SAD. This observation has lead to the hypothesis that the episodic and transient disruption in cerebellar function that characterizes episodic ataxia type 1, a Kv1.1 channelopathy, is due to SAD occurring in the cerebellar cortex.

Acidosis↗

The rat model of type 2 diabetic mellitus and its glycometabolism characters.

To develop a rat model of type 2 diabetic mellitus that simulated the common manifestation of the metabolic abnormalities and resembled the natural history of a certain type 2 diabetes in human population, male Sprague-Dawley rats (4 months old) were injected with low-dose (15 mg/kg) STZ after high fat diet (30% of calories as fat) for two months (L-STZ/2HF). The functional and histochemical changes in the pancreatic islets were examined. Insulin-glucose tolerance test, islet immunohistochemistry and other corresponding tests were performed and the data in L-STZ/2HF group were compared with that of other groups, such as the model of type 1 diabetes (given 50 mg/kg STZ) and the model of obesity (high fat diet). The body weight of rats in the group of rats given 15 mg/kg STZ after high fat diet for two months increased significantly more than that of rats in the group of rats given 50 mg/kg STZ (the model of type 1 diabetes) (595 +/- 33 g vs. 352 +/- 32 g, p<0.05). Fast blood glucose levels for L-STZ/2HF group were 16.92 +/- 1.68 mmol/l, versus 5.17 +/- 0.55 mmol/l in normal control and 5.59 +/- 0.61 mmol/l in rats given high fat diet only. Corresponding values for fast serum insulin were 0.66 +/- 0.15 ng/ml, 0.52 +/- 0.13 ng/ml, 0.29 +/- 0.11 ng/ml, respectively. Rats of type 2 diabetes (L-STZ/2HF) had elevated levels of triglyceride (TG, 3.82 +/- 0.88 mmol/l), and cholesterol(Ch, 2.38 +/- 0.55 mmol/l) compared with control (0.95 +/- 0.15 mmol/l and 1.31 +/- 0.3 mmol/l, respectively) (p<0.05). The islet morphology as examined by immunocytochemistry using insulin antibodies in the L-STZ/2HF group was affected and quantitative analysis showed the islet insulin content was higher than that of rats with type 1 diabetes (P<0.05). We concluded that the new rat model of type 2 diabetes established with conjunctive treatment of low dose of STZ and high fat diet was characterized by hyperglycemia and light impaired insulin secretion function accompanied by insulin resistance, which resembles the clinical manifestation of type 2 diabetes. Such a model, easily attainable and inexpensive, would help further elucidation of the underlying mechanisms of diabetes and its complications.

Animals↗