Biomedical subjects

Z Zhong

Publications and source records attributed to Z Zhong.

At least 19 recordsLinked to original sources

PubMed2000

Human breast cancer specimens: diffraction-enhanced imaging with histologic correlation--improved conspicuity of lesion detail compared with digital radiography.

Seven breast cancer specimens were examined with diffraction-enhanced imaging at 18 keV with a silicon crystal with use of the silicon 333 reflection in Bragg mode. Images were compared with digital radiographs of the specimen, and regions of increased detail were identified. Six of the seven cases (86%) showed enhanced visibility of surface spiculation that correlated with histopathologic information, including extension of tumor into surrounding tissue.

Biopsy, Needle↗

PubMed1999

Evaluation of prognostic criteria for determining hospice eligibility in patients with advanced lung, heart, or liver disease. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

CONTEXT: Many individuals involved with care of the dying advocate expanding access to hospice care for persons with advanced lung, heart, or liver disease. However, to be eligible, these patients generally must have a prognosis for survival of less than 6 months. OBJECTIVE: To test the ability of currently available criteria to identify a population with a survival prognosis of 6 months or less among seriously ill hospitalized patients with 1 of 3 commonly fatal chronic diseases. DESIGN: Validation study using data from the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) phase 1 (June 1989-June 1991) and phase 2 (January 1992-January 1994), with a 6-month follow-up. SETTING AND PATIENTS: Consecutive sample of 2607 seriously ill patients from 5 US medical centers who were hospitalized with chronic obstructive pulmonary disease, congestive heart failure, or end-stage liver disease, and who survived to hospital discharge. MAIN OUTCOME MEASURES: Descriptive and operating characteristics of 5 general and 2 disease-specific clinical criteria for identifying patients with a survival prognosis of 6 months or less, and 3 sets of combination criteria (broad, intermediate, and narrow inclusion) aimed at providing low, medium, and high thresholds for hospice eligibility based on National Hospice Organization guidelines. RESULTS: Seventy-five percent of the sample survived more than 6 months after hospital discharge; 44% expressed a preference for palliative care. Broad inclusion criteria identified 923 patients eligible for hospice care, of whom 70% survived longer than 6 months. Intermediate inclusion criteria identified 300 patients, of whom 65% survived longer than 6 months. Narrow inclusion criteria identified 19 patients, of whom 53% survived longer than 6 months. Sensitivities and specificities of the combination criteria were 41.7% and 66.7% (broad inclusion), 16.2% and 90.1 % (intermediate inclusion), and 1.4% and 99.5% (narrow inclusion), respectively. CONCLUSIONS: These data indicate that for seriously ill hospitalized patients with advanced chronic obstructive pulmonary disease, congestive heart failure, or end-stage liver disease, recommended clinical prediction criteria are not effective in identifying a population with a survival prognosis of 6 months or less.

Adult↗

PubMed1999

Glycine improves survival after hemorrhagic shock in the rat.

This study investigated the effect of glycine on hemorrhagic shock in the rat. Rats were bled to maintain mean arterial pressure at 30-35 mm Hg for 1 h and subsequently resuscitated with 60% shed blood and lactated Ringer's solution. Only 20% of rats receiving saline just prior to resuscitation survived 72 h after shock. Survival was increased by glycine (11.2-90.0 mg/kg, i.v.) in a dose-dependent manner (half-maximal effect = 25 mg/kg) and reached maximal values of 78% at 45 mg/kg. Eighteen hours after resuscitation, creatinine phosphokinase increased 23-fold, transaminases increased 33-fold, and creatinine was elevated 2.4-fold, indicating injury to the heart, liver, and kidney, respectively. Pulmonary edema, leukocyte infiltration, and hemorrhage were also observed. In the kidney, proximal tubular necrosis, leukocyte infiltration, and severe hemorrhage in the outer medullary area occurred in rats receiving saline. Glycine reduced these pathological alterations significantly. It has been reported that oxidative stress and tumor necrosis factor(TNF)-alpha-production are involved in the pathophysiology of multiple-organ injury after shock. In this study, free radical production was increased 4-fold during shock, an effect blocked largely by glycine. Increases in intracellular calcium and production of TNF-alpha by isolated Kupffer cells stimulated by endotoxin were elevated significantly by hemorrhagic shock, alterations which were totally prevented by glycine. Taken together, it is concluded that glycine reduces organ injury and mortality caused by hemorrhagic shock by preventing free radical production and TNF-alpha formation.

Animals↗

PubMed1999

Dietary glycine and renal denervation prevents cyclosporin A-induced hydroxyl radical production in rat kidney.

Cyclosporin A (CsA) nephrotoxicity is associated with renal hypoxia and increases in free radicals in the urine. This study was designed to elucidate the mechanism of radical production caused by CsA. Pretreatment of rats with CsA (25 mg/kg, i.g.) for 5 days decreased glomerular filtration rates by 65%, an effect largely prevented by both dietary glycine (5%) or renal denervation. CsA dissolved in olive oil produced a 6-line alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN)/free radical signal in the urine, which partitioned predominantly into the aqueous phase after chloroform extraction (i.e., it is water soluble). Dimethyl sulfoxide (DMSO) is attacked by the hydroxyl radical to produce a methyl radical; administration of CsA with [(12)C]DMSO produced two radical species in urine, one with hyperfine coupling constants similar to the 4-POBN/methyl radical adduct found in aqueous solution. CsA given with [(13)C]DMSO produced a 12-line spectrum, confirming the formation of hydroxyl radicals. The methyl radical produced by the hydroxyl radical represented 62% of radicals detected in urine but only 15% in bile. Therefore, hydroxyl radicals are produced largely in the kidney. Free radicals in urine were increased about 5-fold by CsA, an effect completely blocked by the inhibitory neurotransmitter, glycine, or by renal denervation. CsA infusion for 30 min increased efferent renal nerve activity 2-fold, and dietary glycine (5%) totally blocked this phenomenon. Taken together, these data are consistent with the hypothesis that CsA increases hydroxyl radical formation by increasing renal nerve activity resulting in vasoconstriction and hypoxia-reoxygenation. Glycine blunts the effect of CsA on the renal nerve, which explains, in part, prevention of nephrotoxicity.

Animals↗

PubMed1999

Molecular and functional characteristics of a protective human monoclonal antibody to serotype 8 Streptococcus pneumoniae capsular polysaccharide.

The structural characteristics and biological activity of human antibodies that are reactive with the capsular polysaccharides of most serotypes of Streptococcus pneumoniae, including serotype 8, are unknown. This paper describes the generation, molecular structure, and protective efficacy of a human monoclonal antibody (MAb) reactive with the capsular polysaccharide of serotype 8 Streptococcus pneumoniae. We generated the immunoglobulin M(kappa) [IgM(kappa)] MAb D11 by Epstein-Barr virus transformation of peripheral lymphocytes from a Pneumovax recipient. Nucleic acid sequence analysis revealed that MAb D11 uses V3-15/V(H)3 and A20/V(kappa) gene segments with evidence of somatic mutation. In vitro studies revealed MAb D11-dependent complement deposition on the capsule of serotype 8 organisms via either the classical or the alternative complement pathway. In vivo, MAb D11 prolonged the survival of both normal and C4-deficient mice with lethal serotype 8 S. pneumoniae infection. Our findings demonstrate that a serotype-specific human IgM with certain structural and functional characteristics was protective in mice lacking a functional classical complement pathway and show that alternative complement pathway activation is an important determinant of pneumococcal protection.

Amino Acid Sequence↗

PubMed1999

Binge drinking disturbs hepatic microcirculation after transplantation: prevention with free radical scavengers.

Disturbances in hepatic microcirculation increase graft injury and failure; therefore, this study evaluates the effects of ethanol on microcirculation after liver transplantation. Donor rats were given one dose of ethanol (5 g/kg) by gavage 20 h before explantation, and grafts were stored in University of Wisconsin solution for 24 h before implantation. Acute ethanol treatment decreased 7-day survival of grafts from about 90 to 30%, increased transaminase release nearly 4-fold, and decreased bile production by 60%. Moreover, portal pressure increased significantly and liver surface oxygen tension decreased about 50%, indicating that ethanol disturbs hepatic microcirculation. Pimonidazole, a 2-nitroimidazole hypoxia marker, was given i.v. to recipients 30 min after implantation, and grafts were harvested 1 h later. Ethanol increased hepatic pimonidazole binding about 3-fold, indicating that ethanol led to hypoxia in fatty grafts. Ethanol also significantly increased free radicals in bile. Catechin (30 mg/kg i.v. upon reperfusion), a free radical scavenger, and Carolina Rinse solution, which contains several agents that inhibit free radical formation, minimized disturbances in microcirculation and prevented pimonidazole adduct formation significantly. These treatments also blunted increases in transaminase release and improved survival of fatty grafts. Destruction of Kupffer cells with GdCl(3) (20 mg/kg i.v. 24 h before explantation) or inhibition of formation of leukotrienes with MK-886 (50 microM in University of Wisconsin or rinse solution) also minimized hypoxia and improved survival after transplantation. Taken together, these results demonstrate that ethanol disturbs hepatic microcirculation, leading to graft hypoxia after transplantation, most likely by activating Kupffer cells and increasing free radical production.

Animals↗

PubMed1999

[The epidemiological study on limb deformities among children in Guangdong Province].

OBJECTIVE: To study the incidence of limb deformities of children in Guangdong province. METHODS: Physical examination on lined-up students and looked over one by one. Detailed examinations of orthopaedics or related subjects were performed on those with susceptive deformity. RESULTS: Results showed that there were 655 cases of limb deformities (0.64%) in 102,313 pupils of 7 to 14 years old, in which 550 cases (83.97%) needed surgical intervention. The incidence of deformity in economically poor areas was 2.88 times higher than those in advanced areas. CONCLUSION: Prevention and cure of limb deformities of children, especially those in rural area, should be addressed and emphasized.

Adolescent↗

PubMed1998

Ethanol, not fat accumulation per se, increases free radical production in a low-flow, reflow liver perfusion model.

BACKGROUND: Ethanol increases primary graft failure after liver transplantation, yet whether it acts via mechanisms involving fat accumulation remains unclear. METHODS: Rats were pair-fed a modified Lieber-DeCarli liquid diet containing 35% (high-fat) or 12% (low-fat) of calories as fat combined with 36% of calories as ethanol or isocaloric maltose-dextrin for 4-5 weeks. Reperfusion injury to the liver was studied using a low-flow, reflow perfusion model and a liver transplantation model, and free radicals were detected using electron spin resonance and the spin trapping technique. RESULTS: As expected, basal hepatic triglycerides were similar in livers from rats fed low- and high-fat control diets. Ethanol did not alter triglyceride levels significantly in rats fed a low-fat diet, but increased values about 2.4-fold in rats fed a high-fat diet. Ethanol increased lactate dehydrogenase release during reperfusion from 10 to 26 IU/g/h in rats fed a low-fat diet and from 17 to 34 IU/g/h in rats fed a high-fat diet, respectively. Portal pressure increased from about 3 to 10.5 cm H2O upon reperfusion in livers from high-fat, ethanol-fed rats, but only reached values of 9.1 in the low-fat, ethanol-fed group. A free radical adduct signal was detected in the bile of livers from ethanol-treated rats, and the magnitude of this signal was similar in livers of ethanol-treated rats fed high- or low-fat diets. However, radical adducts could not be detected in either group in the absence of dietary ethanol. Moreover, 67-77% rats given low-fat or high-fat control diets survived after liver transplantation, but only 11% survived if treated with ethanol. CONCLUSIONS: It is concluded that ethanol plays a major role in hepatic reperfusion injury, most likely via mechanisms involving free radicals. Increased hepatic fat content alone plays only a minor role, probably by causing slight disturbances in the hepatic microcirculation.

Animals↗

PubMed1998

Dietary juniper berry oil minimizes hepatic reperfusion injury in the rat.

Juniper berry oil is rich in 5,11,14-eicosatrienoic acid, a polyunsaturated fatty acid similar to one found in fish oil, yet less prone to peroxidation. Dietary fish oil treatment has been shown to effectively reduce reperfusion injury; therefore, the effects of a diet containing juniper berry oil on hepatic reperfusion injury in a low-flow, reflow reperfusion model were investigated in the rat. Rats were fed semisynthetic diets containing either juniper berry oil, fish oil, or corn oil for 14 to 16 days. Daily food consumption averaged around 20 g/d in both the control and treatment groups; average daily weight gain was around 4 g per 100 g rat weight in all three groups studied, and there were no significant differences in these parameters. Livers were initially perfused at low-flow rates to induce pericentral hypoxia followed by a 40-minute reperfusion period. Peak lactate dehydrogenase (LDH) release during reflow averaged 44 U/g/h in the corn oil group and 32 U/g/h in the fish oil group, but was only 21 U/g/h as a result of juniper berry oil treatment. Malondialdehyde (MDA), an end-product of lipid peroxidation, reached a maximum value of 62 nmol/g/h in the corn oil group, but only reached 43 nmol/g/h and 34 nmol/g/h in the fish oil and juniper berry oil groups, respectively. Both juniper berry oil and fish oil treatment improved rates of bile flow from 25 microL/g/h (corn oil) to 36 and 38 microL/g/h, respectively. Importantly, juniper berry oil reduced cell death in pericentral regions of the liver lobule by 75%. Trypan blue distribution time, an indicator of the hepatic microcirculation, was reduced by approximately 25% with fish oil and over 50% by juniper berry oil diets compared with corn oil controls. The rates of entry of fluorescein-dextran, a dye confined to the vascular space, were increased 1.8- and 2.6-fold, and rates of outflow were increased 4.4- and 4.3-fold by fish oil and juniper berry oil, respectively, also reflecting improved microcirculation. Juniper berry oil also blunted increases in intracellular calcium and release of prostaglandin E2 (PGE2) by cultured Kupffer cells stimulated by endotoxin. These results are consistent with the hypothesis that feeding a diet containing juniper berry oil reduces reperfusion injury by inhibiting activation of Kupffer cells, thus reducing vasoactive eicosanoid release and improving the hepatic microcirculation in livers undergoing oxidant stress.

Animal Feed↗

PubMed1998

Generation of lipid free radicals by adherent leukocytes from transplanted rat liver.

The production of free radicals in blood correlates with primary nonfunction of transplanted livers, but the source of the free radicals is unknown. The purpose of this study was to determine if adherent leukocytes in the transplanted liver are responsible for the radicals detected in blood. First, a new method to harvest adherent leukocytes from the liver without enzymatic digestion was developed and characterized by transplanting livers from ethanol-treated rats, which increases primary nonfunction, and from saline-treated controls. Free radicals were then detected in isolated leukocytes using the spin-trapping technique and electron spin resonance (ESR) spin spectroscopy. Livers were perfused with a balanced salt solution (200 ml), followed by a Ca(2+)-free solution containing EGTA and heparin (400 ml). Perfusion with Ca(2+)-free buffer removed greater than 90% of all adherent leukocytes from saline-treated livers and nearly 80% of all leukocytes from fatty livers without removing Kupffer cells. Transplanted fatty livers from rats given ethanol contained significantly more adherent leukocytes (5.0 x 10(7) cells/liver) than grafts from control donors (3.2 x 10(7) cells/liver) and almost double the number of adherent neutrophils and monocytes. Moreover, adherent white blood cells from transplanted livers produced the same three free radical species that have been detected previously in blood; however, cells from ethanol-treated livers produced about five times more radical adducts. These data show that adherent white blood cells produce free radicals that are important in the mechanism of primary graft nonfunction.

Animals↗

PubMed1998

A human IgM monoclonal antibody prolongs survival of mice with lethal cryptococcosis.

Antifungal therapy cannot eradicate Cryptococcus neoformans infections in immunosuppressed patient groups. Therefore, adjunctive antibody-based therapy is being considered to enhance host immune responses to C. neoformans. To characterize potentially protective reagents, the idiotypic repertoire of human antibodies to cryptococcal glucuronoxylomannan (GXM) elicited by the investigational conjugate vaccine GXM-tetanus toxoid was examined. The variable genes used by human antibodies to GXM were analyzed with an antigen-based ELISA and mouse monoclonal antibodies (MAbs) that recognize determinants of human VH1, VH3, and VH4 gene segments. Antibodies to GXM were shown to use VH3 gene segments, and antibodies with the greatest binding to GXM also bound to protein A. A VH3-positive human monoclonal IgM prolonged survival of C. neoformans-infected mice. This is the first report that a human antibody is protective against C. neoformans. These results suggest that human MAbs may have promise as therapeutic reagents against cryptococcosis.

Animals↗

PubMed1998

Characterization of a murine monoclonal antibody to Cryptococcus neoformans polysaccharide that is a candidate for human therapeutic studies.

The murine monoclonal antibody (MAb) 18B7 [immunoglobulin G1(kappa)] is in preclinical development for treatment of Cryptococcus neoformans infections. In anticipation of its use in humans, we defined the serological and biological properties of MAb 18B7 in detail. Structural comparison to the related protective MAb 2H1 revealed conservation of the antigen binding site despite several amino acid differences. MAb 18B7 was shown by immunofluorescence and agglutination studies to bind to all four serotypes of C. neoformans, opsonize C. neoformans serotypes A and D, enhance human and mouse effector cell antifungal activity, and activate the complement pathway leading to deposition of complement component 3 (C3) on the cryptococcal capsule. Administration of MAb 18B7 to mice led to rapid clearance of serum cryptococcal antigen and deposition in the liver and spleen. Immunohistochemical studies revealed that MAb 18B7 bound to capsular glucuronoxylomannan in infected mouse tissues. No reactivity of MAb 18B7 with normal human, rat, or mouse tissues was detected. The results show that both the variable and constant regions of MAb 18B7 are biologically functional and support the use of this MAb in human therapeutic trials.

Amino Acid Sequence↗

PubMed1998

Antifungal activity of a human antiglucuronoxylomannan antibody.

The human immunoglobulin M (IgM) monoclonal antibody (MAb) 2E9 binds the glucuronoxylomannan (GXM) of Cryptococcus neoformans serotypes A, B, and D. This study was undertaken to determine the opsonic efficacy of 2E9 and its ability to promote the antifungal activity of human polymorphonuclear neutrophils (PMNs) against C. neoformans. We incubated purified PMNs with fluorescein isothiocyanate-labeled C. neoformans cells that were treated with the GXM IgM 2E9, IgM antibodies that do not bind GXM, and rabbit and human factor-B-deficient serum as complement sources. PMN-associated C. neoformans cells fluoresced and were detected with a fluorescence-activated cell sorter. The amount of phagocytosis was defined as the percent fluorescing PMNs, which was 37% for yeast cells opsonized with 2E9 plus rabbit serum and 57% for yeast cells opsonized with 2E9 plus factor-B-deficient serum. Phagocytosis was significantly greater for yeast cells that were treated with 2E9 plus a complement source than for yeast cells treated with the complement sources alone or treated with the control IgMs alone or with the complement sources. Fluorescence quenching and light and electron microscopy of the phagocytosis mixtures revealed that 2E9-opsonized yeast cells were internalized by PMNs. Maximal inhibition of C. neoformans growth occurred when PMNs were cocultured with yeast cells that were opsonized with 2E9 plus a complement source. Our data demonstrate that the human GXM IgM 2E9 can mediate PMN phagocytosis and C. neoformans growth inhibition in vitro. These findings strongly suggest that antibody-mediated deposition of complement components on the cryptococcal capsule can augment PMN complement receptor-mediated antifungal activity. Antibody activation of complement-mediated effector cell antifungal mechanisms may play a role in host defense against cryptococcosis and represents a goal for the use of MAbs to treat or prevent human C. neoformans infections.

Antibodies, Fungal↗

PubMed1998

Stimulation of oxygen uptake by prostaglandin E2 is oxygen dependent in perfused rat liver.

The aim of this study was to determine if the effect of prostaglandin E2 (PGE2) on hepatic oxygen uptake was affected by oxygen tension. Livers from fed female Sprague-Dawley rats were perfused at normal or high flow rates (4 or 8 ml . g-1 . min-1) to vary local oxygen tension within the liver lobule. During perfusion at normal flow rates, PGE2 (5 microM) infusion increased oxygen uptake by about 50 micromol . g-1 . h-1; however, when livers were perfused at high flow rates, the increase was nearly twice as large. Simultaneously, glucose output was increased rapidly by about 50%, whereas glycolysis was decreased about 60%. When flow rate was held constant, increases in oxygen uptake due to PGE2 were proportional to oxygen delivery. Infusion of PGE2 into livers perfused at normal flow rates increased state 3 rates of oxygen uptake of subsequently isolated mitochondria by about 25%; however, rates were increased 50-75% in mitochondria isolated from livers perfused at high flow rates. Thus it is concluded that PGE2 stimulates oxygen uptake via mechanisms regulated by oxygen tension in perfused rat liver. High flow rates also increased basal rates of oxygen uptake: this increase was prevented by inactivation of Kupffer cells with GdCl3. In addition, conditioned medium from Kupffer cells incubated at high oxygen tension (75% oxygen) stimulated oxygen uptake of isolated parenchymal cells by >30% and elevated PGE2 production about twofold compared with Kupffer cells exposed to normal air-saturated buffer (21% oxygen). These effects were blocked completely by both indomethacin and nisoldipine. These data support the hypothesis that oxygen stimulates Kupffer cells to release mediators such as PGE2 which elevate oxygen consumption in parenchymal cells, possibly by mechanisms involving cyclooxygenase and calcium channels.

Animals↗

PubMed1998

Cyclosporin A increases hypoxia and free radical production in rat kidneys: prevention by dietary glycine.

The major side effect of cyclosporin A is severe nephrotoxicity. It is likely that cyclosporin A causes vasoconstriction leading to hypoxia-reperfusion injury; therefore, these experiments were designed to attempt to obtain physical evidence for hypoxia and free radical production in kidney following cyclosporin A. Rats were treated daily with cyclosporin A (25 mg/kg ig) for 5 days, and pimonidazole, a hypoxia marker, was injected 2 h after the last dose of cyclosporin A. A dose of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) was injected 3 h after cyclosporin A to trap free radicals. Cyclosporin A doubled serum creatinine and decreased glomerular filtration rates by 65% as expected. Pimonidazole adduct binding in the kidney was increased nearly threefold by cyclosporin A, providing physical evidence for tissue hypoxia. Moreover, cyclosporin A increased 4-POBN/radical adducts nearly sixfold in the urine but did not alter levels in the serum. Glycine, which causes vasodilatation and prevents cyclosporin A toxicity, minimized hypoxia and blocked free radical production; however, it did not alter cyclosporin A blood levels. These results demonstrate for the first time that cyclosporin A causes hypoxia and increases production of a new free radical species exclusively in the kidney. Therefore, it is concluded that cyclosporin A causes renal injury by mechanisms involving hypoxia-reoxygenation, effects which can be prevented effectively by dietary glycine.

Animals↗

PubMed1998

Kupffer cell-dependent reperfusion injury in liver transplantation: new clinically relevant use of glycine.

Kupffer cell-dependent reperfusion injury occurs to the liver following transplantation, most often in fatty livers which fail most frequently due to primary nonfunction. Failure was largely blocked with Carolina rinse solution, which contains glycine, and prevents the activation of Kupffer cells. Furthermore, gentle in situ organ manipulation, which cannot be prevented using standard harvesting techniques, has a detrimental effect on survival. These effects were also prevented by glycine. Since proteolytic activity is increased in both fatty and manipulated livers, amino acids were measured in rinse effluents collected at harvest. A combination of four amino acids correlated with graft function. It is concluded that glycine could be beneficial in clinical liver transplantation to prevent reperfusion injury, and that amino acids measured at harvest may predict graft function.

Fatty Liver↗

PubMed1997

Prevention of cyclosporine-induced nephrotoxicity with dietary glycine.

BACKGROUND: The nonessential amino acid glycine has been used previously to prevent hypoxic and ischemic injury to kidney tissue in vitro. Furthermore, it was recently shown that glycine prevents activation of macrophages and neutrophils in vitro. Because there is some evidence that the immunosuppressant cyclosporine causes nephrotoxicity through a hypoxia-reoxygenation mechanism that could involve infiltration and activation of macrophages and neutrophils, we hypothesized that dietary glycine could prevent this injury. METHODS: Rats were fed a diet containing glycine (5%) or a control diet for 3 days before cyclosporine treatment. To produce nephrotoxicity, cyclosporine (25 mg/kg daily by gavage) was administered for 28 days while animals were maintained on glycine or control diets. Serum creatinine, urea, glomerular filtration rates, and kidney histology were evaluated in different treatment groups. RESULTS: All rats gained weight; however, overall weight gain in the cyclosporine, glycine, and cyclosporine+glycine groups was significantly less by about 40% compared with the control group. Diet consumption was not statistically different between the groups. As expected, cyclosporine caused kidney damage in the rats fed control diet, reflected in significantly elevated serum urea and creatinine. In addition, cyclosporine treatment decreased glomerular filtration rate by nearly 70%, caused proximal tubular dilation and necrosis as well as increased macrophage and neutrophil infiltration into the kidney. Dietary glycine prevented or minimized kidney damage due to cyclosporine in all parameters studied nearly completely. Furthermore, feeding glycine for up to 1 month had no detrimental effect on kidney function. CONCLUSIONS: Dietary glycine is a safe and effective treatment to reduce the nephrotoxicity of cyclosporine.

Animal Feed↗

PubMed1997

STAT signaling is active during early mammalian development.

Cytokine activation of gene expression can be mediated through signal transducer and activator of transcription (STAT) signaling pathways resulting in expression of target genes. Because many cytokines have important regulatory roles during early development, we wanted to ascertain whether STAT signaling was also active at this time and could therefore have important roles in mediating developmental processes. We have found that Stat1 and Stat3 mRNAs are present in both maternal and extraembryonic tissues during early postimplantation stages of murine development. Furthermore, analyses of STAT activity in E4.5-E9.5 decidual swellings by electrophoretic mobility shift assay demonstrated that Stat3 protein was active during this early developmental period. The identification of activated Stat3 demonstrates that STAT signaling functions during early postimplantation development in the mouse are likely to be important during early embryogenesis.

Animals↗