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Biomedical subjects

Iris Barshack

Publications and source records attributed to Iris Barshack.

At least 19 recordsLinked to original sources
PubMed2006

Erythropoietin improves myocardial performance in doxorubicin-induced cardiomyopathy.

AIMS: Doxorubicin (Dox) is a potent chemotherapeutic agent associated with severe cardiotoxicity. Erythropoietin (Epo) has recently been shown to exhibit proangiogenic properties related to endothelial progenitor cell (EPC) mobilization. We tested the hypothesis that EPC are compromised in rats with Dox-induced cardiotoxicity and correction of this functional impairment by treatment with Epo could result in attenuation of myocardial dysfunction. METHODS AND RESULTS: Wistar rats were either treated with two different doses of Epo (20U or 200U) or PBS (n = 40 in each group) for four consecutive weeks, followed by Dox administration. In a second study, EPC obtained from healthy rats were transfused intravenously (n = 20/group) prior to induction of Dox cardiomyopathy. EPC from healthy subjects were evaluated for their proliferative and migratory properties in the presence or absence of Dox and Epo pre-treatment. Echocardiography demonstrated an improvement in fractional shortening (FS) in Epo-treated rats. Epo treatment was associated with a reduced mortality in both Epo-treated groups. Circulating EPC numbers were three times higher in Epo-treated compared with non-treated animals. Adhesive properties, migration, and tube formation capacity in matrigel of EPCs from both Epo-treated groups as compared with controls were significantly enhanced. EPC transfer to Dox-treated rats led to functional myocardial improvement equivalent to the protection afforded by treatment with Epo. In EPC obtained from humans, pre-incubation with Epo significantly attenuated the anti-proliferative and anti-migratory effects of treatment with Dox. CONCLUSION: Epo treatment is potentially protective against myocardial dysfunction induced by Dox. These effects are partially mediated by enhancement in the number of EPC and their functional properties.

Animals↗
PubMed2006

Granular myringitis: Incidence and clinical characteristics.

OBJECTIVE: To examine the incidence and the clinical features of granular myringitis (GM). STUDY DESIGN: A 2-year prospective cohort study. SETTING: A primary otolaryngology clinic affiliated with a tertiary academic referral center. PATIENTS: All-aged patients diagnosed with GM who had no apparent middle ear disease or did not undergo ear surgery. INTERVENTION: Otoscopy and bacteriologic and histopathologic studies. MAIN OUTCOME MEASURES: Granular myringitis was noted in 0.41% of patient's population presenting different forms. RESULTS: Granular myringitis was detected in 26 patients. Recurrent infection occurred in seven (26.9%) and bilateral GM in five patients (19.2%). Perforation of the tympanic membrane (TM) was noted in eight patients (30.7%), six of which closed spontaneously. Otoscopic findings could be classified into three grades: focal de-epithelization (in 10), focal polypoid granulations (in 13), and diffuse polypoid formation over the entire TM (in 3). Histopathologic examination disclosed tiny fragments of granulation tissue infiltrated by nonspecific chronic and acute inflammatory reaction. CONCLUSION: Granular myringitis is encountered not infrequently in primary otolaryngology practice and presented different forms, recurrent episodes, and bilateral involvement. Topical application of antibiotics or caustic agents was successful in all cases. Perforation of the TM may develop and resolve spontaneously during the course of the disease.

Adolescent↗
PubMed2006

Endoscopic ultrasound staging of rectal cancer: diagnostic value before and following chemoradiation.

BACKGROUND: Endoscopic ultrasound (EUS) has been shown to be a reliable tool for staging rectal cancer. Nevertheless, the accuracy of EUS after chemoradiation remains unclear; therefore the purpose of the present paper was to compare the accuracy of EUS staging for rectal cancer before and following chemoradiation. METHODS: Patients with rectal cancer undergoing EUS staging were stratified into two groups. Group I consisted of 66 patients who underwent surgery following EUS staging without preoperative chemoradiation. Group II consisted of 25 patients who had EUS evaluation following chemoradiation. The EUS staging was compared to surgical/pathological staging. RESULTS: The accuracy of the T staging for group I was 86% (57/66). Inaccurate staging was mainly associated with overstaging EUS T2 tumors. The accuracy of the N staging for group I was 71% (47/66). The accuracy of EUS for a composite T and N staging relevant to treatment decisions in group I was 91%. In group II, the accuracy of T and N staging was 72% (18/25) and 80% (20/25), respectively. Overstaging EUS T3 tumors accounted for most inaccurate staging. The EUS staging predicted post-chemoradiation T0N0 stage correctly in only 50% of cases. CONCLUSIONS: Preoperative staging of rectal cancer by EUS is a useful modality in determining the need for preoperative chemoradiation. The EUS T staging following chemoradiation appears to be less accurate. Detection of complete response may be insufficient for selecting patients for limited surgical intervention.

Adult↗
PubMed2006

Vascular wall maturation and prolonged angiogenic effect by endothelial-specific platelet-derived growth factor expression.

BACKGROUND: The implementation of angiogenic gene therapy at clinics is hindered by the transience of the therapeutic effect. Recruiting vascular wall smooth muscle cells, a process termed 'maturation', can stabilize newly formed vessels. OBJECTIVE: To induce angiogenesis followed by vessel maturation in a murine ischemic limb model by endothelial cell-specific promoter regulated expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-BB (PDGF-BB). METHODS: We constructed adenoviral vectors containing angiogenic factors VEGF and PDGF-B regulated by a modified preproendothelin-1 (PPE-1-3x) promoter and investigated their angiogenic effect in a murine ischemic limb model. RESULTS: VEGF gene therapy increased perfusion and the vessel density in the limb shortly after expression with PPE-1-3x promoter or cytomegalovirus (CMV) promoter vectors, but only PPE-1-3xVEGF treatment exhibited a sustained effect. Expression of PDGF-B by PPE-1-3x promoter resulted in morphological maturation of the vasculature and further increased the perfusion, while nonspecific expression of PDGF-B with CMV promoter had no therapeutic effect. Regulation of dual therapy with VEGF and PDGF-B by PPE-1-3x promoter resulted in an early-onset, sustained angiogenic effect accompanied by vessel maturation. CONCLUSIONS: Systemic gene therapy with the angiogenic factors VEGF and PDGF-B under angiogenic- endothelial cell-specific regulation was effective in inducing functionally and morphologically mature vasculature.

Adenoviridae↗
PubMed2005

Inhibition of carcinogenesis in transgenic mouse models over-expressing 15-lipoxygenase in the vascular wall under the control of murine preproendothelin-1 promoter.

Oxygenases are a family of enzymes that dioxygenate unsaturated fatty acids, thus initiating membrane oxidation and signaling molecule synthesis. The lipoxygenases (LOs), a family of lipid-peroxidizing enzymes that induce structural and metabolic changes in the cell in a number of pathophysiological conditions, belong to the oxygenases family. This class of enzymes has several subgroups, named 5-, 8-, 12- and 15-LOs, and these LO-isoforms are capable of oxygenating arachidonic and linoleic acid. 15-LOs were reported to play an inhibitory role in tumor angiogenesis and, consequently, they slow down carcinogenesis. It has been suggested that its anti-carcinogenic effect is conferred by promoting cell differentiation and apoptosis. Using transgenic mice that over-express 15-LO-1 in endothelial cells under the regulation of the murine preproendothelin-1 promoter, we studied its effect on tumor and metastasis growth. We found that 15-LO-1 inhibited tumor and metastasis growth in the transgenic mice in two different models of cancer (mammary gland and Lewis lung carcinoma). This inhibition was concomitant with a higher number of apoptotic cells in the metastases of the transgenic mice and with a complicated network of multiple small blood vessels. This finding targets 15-LO as a new candidate in the treatment of carcinogenesis.

Animals↗
PubMed2005

Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells.

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue.

Adenoviridae↗
PubMed2005

The effect of tyrphostin AG-556 on intimal thickening in a mouse model of arterial injury.

BACKGROUND: Inflammation has been shown to play an important role in promoting the response to arterial injury and proinflammatory cytokines, such as tumor necrosis factor (TNF) alpha, are candidate mediators. AG-556 is a tyrosine kinase inhibitor proven to be effective in a model of multiple sclerosis-like syndrome in mice due to its immunomodulating effect. In the current study, we investigated the effect of the tyrphostin AG-556 on neointimal thickening and cytokine profile in a model of arterial injury in the mouse. METHODS: Injury was induced by external cuff placement on the left femoral artery of wild-type C57BL/6 mice. AG-556 dissolved in DMSO was injected intraperitoneally daily to the injured mice in a dosage of 2 mg/mouse. Control mice received DMSO injections. Histological analysis was carried out to assess neointimal formation. Splenocytes were cultured in the absence and presence of a mitogen for evaluation of thymidine incorporation and cytokine production. RESULTS: AG-556 treatment significantly attenuated intimal thickening (43,000+/-17,000 microm2; n=11) when compared to DMSO administration (286,000+/-127,000 microm2; n=10; P<0.05). Basal interferon-gamma production by splenocytes from AG-556-treated mice was increased by approximately 20-fold in comparison with levels in DMSO-treated animals, whereas Con-A induced secretion of the cytokine was similar between both groups. Levels of TNF-alpha, IL-4 and IL-10 in the culture supernatant from treated and non-treated animals did not differ significantly. CONCLUSION: The tyrosine kinase inhibitor AG-556 may have a role in the reduction of intimal thickening. The effect could be mediated via an immune modulating effect involving a significant increase in the smooth muscle cell inhibitory cytokine IFN-gamma.

Animals↗
PubMed2005

Transfer of endothelial progenitor cells improves myocardial performance in rats with dilated cardiomyopathy induced following experimental myocarditis.

Endothelial progenitor cells (EPCs) home to sites of tissue injury and differentiate into mature endothelial cells. Their transfer feasibility has been proven in models of hindlimb ischemia and myocardial infarction. We investigated, the effect of delivery of spleen-derived EPC in a rat model of inflammatory-mediated myocardial damage. Male Lewis rats (N=25) were immunized against myosin. Healthy donor Lewis rats were sacrificed, their spleens harvested, separated on Ficoll gradient centrifugation, and grown on fibronectin coated plates with endothelial cell medium for 5 days. Ten days after myosin immunization, spleen cell derived EPC were collected, and labeled 2 x 10(7) cells per rat were injected into the femoral vein of diseased rats. Cell transplantation was repeated twice, 2 and 4 weeks after initial cell transfer. Rats with inflammatory-mediated cardiomyopathy exhibited a significant mobilization of EPC from the bone marrow to the periphery and their ability to adhere to fibronectin, mature endothelial cells and cultured cardiomyocytes was significantly reduced when compared to healthy rats. Transfer of EPC resulted in a functional improvement in cardiac performance evident by higher fractional shortening by echocardiography (a 15% increase). Histological studies exhibited reduced scar tissue and thickened ventricular walls in rats receiving EPC as compared with untreated animals. EPC transfer is effective in attenuating myocardial damage in a model of non-ischemic dilated cardiomyopathy.

Animals↗
PubMed2004

Vitamin A exerts its activity at the transcriptional level in the small intestine.

THE AIM OF THIS STUDY: was to examine the effects of vitamin-A deficiency on the small intestinal morphology and on brush-border enzyme function and expression. METHODS: Weanling male rats were fed a vitamin-A deficient (VAD), sufficient (VAS), or supplemented (VASUP) diet, or were pair-fed (PF) with the VAD rats. Average food intakes were not different among the groups. RESULTS: From days 35 to 42, the body weight of VAD rats began to plateau, whereas the other groups, including the PF rats, continued to gain weight. At days 48 to 51, the final mean body weight of VAD rats was significantly lower than that of PF, VAS and VASUP rats (P < 0.05). Serum and liver retinol levels were lower in VAD rats (by 85 % and 99%, respectively) and higher in the VASUP group (by 126 % and 160%, respectively) compared to the VAS group (P < 0.01). Histological examination of the jejunum revealed that in VAD rats the villi were shorter and thicker and there was an elevation in crypt depth relative to the other treatment groups. Infiltration of inflammatory cells was also observed in the jejunum of most of the VAD rats, but not in rats from other groups. Biochemical assays revealed that in VAD rats, alkaline phosphatase (ALP) and sucrase-isomaltase (SI) activities are significantly decreased in the jejunum, compared to PF, VAS and VASUP groups (P < 0.01). ALP activity was decreased in the duodenum of VAD rats as well. By comparison, amino-peptidase (AP) activity per mg protein in the jejunum and ileum of VAD rats was significantly increased compared to VAS and VASUP rats (P < 0.01), but was not different from PF rats. In all of the small intestinal sections, mRNA expression of all three brush-border enzymes relative to beta-actin were significantly lower in VAD rats than in the other treatment groups. SI was similarly expressed in all of the small intestinal organs, whereas AP and ALP expression varied. CONCLUSIONS: Our results suggest that vitamin-A deficiency modifies the maturation and differentiation processes of the small intestinal mucosa at the transcriptional and post-transcriptional levels respectively. This in turn may be one explanation for the alteration or elimination of nutrient digestion and absorption during VAD.

Alkaline Phosphatase↗
PubMed2004

Zinc reduces intimal hyperplasia in the rat carotid injury model.

BACKGROUND: The response to arterial injury following balloon dilatation is known to involve proliferative and inflammatory processes. The current widespread use of stents to maintain arterial patency not only does not eliminate but possibly exaggerates the proliferative and inflammatory phenotype and although drug-eluting stents are available, their long-term safety is yet to be determined. Zinc is a trace element that serves as a cofactor of many enzymes. Interestingly, it has been shown to have anti-inflammatory and anti-proliferative properties. We thus sought to investigate its effect on smooth muscle cell proliferation and intimal thickening in the rat carotid artery injury model. METHODS AND RESULTS: Smooth muscle cells (SMC) were cultured from carotid arteries of rats and proliferation was assessed by thymidine incorporation after exposure to different concentrations of zinc. Next, carotid artery injury was induced in rats by balloon dilatation and they were either treated with I.P injections of zinc or PBS for 2 weeks until sacrifice for assessment of neointimal formation and lumen area. Zinc inhibited in vitro SMC proliferation in a dose-dependent manner. In vivo, zinc treatment resulted in a 50% reduction in neointimal area and a significant decrease in neointimal/media ratio with no significant change in lumen area. CONCLUSION: Thus, zinc appears to reduce neointimal growth and should be tested by local delivery systems including stent coatings.

Animals↗
PubMed2004

Allicin inhibits spontaneous and TNF-alpha induced secretion of proinflammatory cytokines and chemokines from intestinal epithelial cells.

BACKGROUND & AIMS: Allicin, the active substance of fresh crushed garlic has different biological activities and was implicated as an anti-inflammatory agent. Epithelial cells have an important role in intestinal inflammation. The aim of this study was to assess the immunomodulatory effect of allicin on intestinal epithelial cells. METHODS: The spontaneous and TNF-alpha-stimulated secretion of IL-1beta, IL-8, IP-10 and MIG from HT-29 and Caco-2 cells was tested with, or without pretreatment with allicin. Cytokine secretion was assessed using ELISA and expression of mRNA was determined by an RNA protection assay. RESULTS: Allicin markedly inhibited the spontaneous and TNF-alpha -induced secretion of IL-1beta, IL-8, IP-10 and MIG from the two different cell lines in a dose-dependent manner and suppressed the expression of IL-8 and IL-1beta mRNA levels. In addition, allicin suppressed the degradation of IkappaB. No effect on cell viability was noted. CONCLUSIONS: These observations indicate that allicin exerts an inhibitory immunomodulatory effect on intestinal epithelial cells and suggest that allicin may have the potential to attenuate intestinal inflammation.

Anti-Infective Agents↗
PubMed2004

The effect of early and late treatment with the tyrphostin AG-556 on the progression of experimental autoimmune myocarditis.

Experimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder; the involvement of TNF-alpha in this disorder has been demonstrated. EAM represents a model for human autoimmune myocarditis, a condition for which no optimal treatment is currently available. Tyrphostins AG-126 and AG-556 were previously shown to reduce TNF-alpha production and its end-organ cytotoxicity, thus proving beneficial in animal models of septic shock and experimental autoimmune encephalomyelitis. To study the effects of AG-126 and AG-556 on EAM, we induced the disorder in male Lewis rats through immunization against myosin and subsequently treated the rats with both agents or the control DMSO both before and after the appearance of myocardial inflammation. AG-556 administered daily for 21 days from the day of EAM induction, significantly reduced the severity of myocarditis. Similarly, AG-556 administered for an additional 10 days after myosin immunization (when signs of inflammation are already present) attenuated the progression of myocarditis, though AG-126 did not. TNF-alpha and IFN-gamma production by in vitro sensitized splenocytes from AG-556-treated rats was significantly diminished as compared with control cells from EAM animals. Thus, AG-556 may represent a novel strategy of ameliorating the progression of myocarditis without non-selectively compromising the immune system.

Animals↗
PubMed2004

Dietary iron affects inflammatory status in a rat model of colitis.

Iron deficiency anemia is a common feature in inflammatory bowel disease, and oral supplementation is one of the mainstay therapies. However, there is some concern that oral iron supplementation may lead to oxidative stress and exacerbation of inflammation. Our objective was to study the effect of severely deficient, moderately deficient, normal and high iron status on oxidative stress and the course of inflammation in a rat model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The rats were randomly assigned to receive the low-iron diet for 3 (moderately iron-deficient group, n = 16) or 5 (severely iron-deficient group, n = 16) wk, the normal iron diet for 2 wk (normal iron group, n = 16) or the high-iron diet for 2 wk (high-iron group, n = 16). Malondialdehyde concentration, electroparamagnetic resonance measurement, myeloperoxidase activity, and histological analysis were used to evaluate oxidative stress. Noncolitic rats in the high-iron group had higher oxidative stress parameters than those in the other groups. The induction of colitis resulted in severe inflammatory changes in the high-iron and severely iron-deficient groups, and produced higher histological scores in the colon of the normal and high-iron groups. Iron overload, oxidative stress, and inflammation were lower in the moderately iron-deficient group compared with the other 3 groups. In conclusion, we suggest that low rather than normal or high iron supplementation should be considered for the treatment of iron deficiency in inflammatory bowel disease.

Animals↗
PubMed2004

Transcription-controlled gene therapy against tumor angiogenesis.

A major drawback of current approaches to antiangiogenic gene therapy is the lack of tissue-specific targeting. The aim of this work was to trigger endothelial cell-specific apoptosis, using adenoviral vector-mediated delivery of a chimeric death receptor derived from the modified endothelium-specific pre-proendothelin-1 (PPE-1) promoter. In the present study, we constructed an adenovirus-based vector that targets tumor angiogenesis. Transcriptional control was achieved by use of a modified endothelium-specific promoter. Expression of a chimeric death receptor, composed of Fas and TNF receptor 1, resulted in specific apoptosis of endothelial cells in vitro and sensitization of cells to the proapoptotic effect of TNF-alpha. The antitumoral activity of the vectors was assayed in two mouse models. In the model of B16 melanoma, a single systemic injection of virus to the tail vein caused growth retardation of tumor and reduction of tumor mass with central tumor necrosis. When the Lewis lung carcinoma lung-metastasis model was applied, i.v. injection of vector resulted in reduction of lung-metastasis mass, via an antiangiogenic mechanism. Moreover, by application of the PPE-1-based transcriptional control, a humoral immune response against the transgene was avoided. Collectively, these data provide evidence that transcriptionally controlled, angiogenesis-targeted gene therapy is feasible.

Adenoviridae↗
PubMed2003

Inhibition of intimal thickening in the rat carotid artery injury model by a nontoxic Ras inhibitor.

BACKGROUND: Neointimal formation with and without previous vascular injury is common after balloon dilation and in transplant arteriosclerosis. It involves proliferation and migration of medial smooth muscle cells and inflammation, processes that are regulated by Ras proteins and their down-stream effectors. Farnesylthiosalicylate (FTS) is a Ras inhibitor that interferes with Ras membrane anchorage and affects Ras proteins in their active state. In the present study, we tested the hypothesis that systemic administration of FTS will suppress intimal thickening in the rat carotid injury model. METHODS AND RESULTS: The effects of FTS on rat vascular smooth muscle cells (VSMC) and splenocytes proliferation were evaluated in vitro. The in vivo effects of FTS on the neointima of balloon-injured male Wistar rats, treated daily for 2 weeks with FTS (5 mg/kg weight, intraperitoneally) were evaluated by determination of Ras, Ras-GTP, and active ERK levels (3 days after injury), and by quantitative determination of the extent of intimal thickening and immunohistochemistry for Ras, iNOS, NFkB, and Ki-67 (2 weeks after injury). FTS inhibited VSMC and splenocyte proliferation as well as interferon-gamma secretion by splenocytes in a dose-dependent manner. Compared with controls, FTS treatment resulted in a strong decrease in Ras-GTP and active ERK, and it significantly reduced intimal thickening after the injury. Ras expression appeared predominantly at areas of neointima regardless of the treatment group. NFkB and iNOS-positive cell numbers were reduced in sections of FTS treated rats. CONCLUSIONS: FTS appears to act as a potent inhibitor of intimal thickening in a model of experimental arterial injury.

Animals↗
PubMed2003

Functional, persistent, and extended liver to pancreas transdifferentiation.

Pancreatic and duodenal homeobox gene-1 (PDX-1) regulates pancreas development during embryogenesis, whereas in the adult it controls beta-cell function. Here we analyze whether PDX-1 functions as a pancreatic differentiation factor and a bona fide master regulator when ectopically expressed in mature fully differentiated liver in vivo. By ectopic and transient PDX-1 expression in liver in vivo, using the first generation recombinant adenoviruses, we demonstrate that PDX-1 induces in liver a wide repertoire of both exocrine and endocrine pancreatic gene expression. Moreover, PDX-1 induces its own expression (auto-induction), which in turn may explain the long lasting nature of the "liver to pancreas" transdifferentiation. Insulin as well glucagon-producing cells are mainly located in the proximity of hepatic central veins, possibly allowing direct hormone release into the bloodstream, without affecting normal hepatic function. Importantly, we demonstrate that hepatic insulin production triggered by Ad-CMV-PDX-1 recombinant adenovirus administration is functional and prevents streptozotocin-induced hyperglycemia in Balb/c mice even 8 months after the initial treatment. We conclude that PDX-1 plays an important instructive role in pancreas differentiation, not only from primitive gut endoderm but also from mature liver. Transconversion of liver to pancreas may serve as a novel approach for generating endocrine-pancreatic tissue that can replace malfunctioning beta-cells in diabetics.

Animals↗
PubMed2003

Tyrphostin AG-556 reduces myocardial infarct size and improves cardiac performance in the rat.

TNF-alpha is a proinflammatory cytokine, abundantly expressed after myocardial infarction. It has been suggested that it exhibits myocardial suppressive and cytotoxic effects. AG-556 is a tyrosine kinase inhibitor synthesized based on its ability to reduce TNF-alpha production and cell toxicity, and to improve experimental models mediated by TNF-alpha (i.e., peritontitis and experimental autoimmune encephalomyelitis). Daily, for 7 days, rats were injected ip with either AG-556 dissolved in DMSO or with the control vehicle. Infarct size was determined in the hearts as well as in fibrous scar formation. Cardiac TNF-alpha expression was evaluated by ELISA and immunohistochemistry. Functional hemodynamic parameters were evaluated employing echocardiography prior to sacrifice. AG-556 treatment reduced MI size at 7 days with a parallel effect on fibrous tissue formation. TNF-alpha production by splenocytes was reduced upon AG-556 treatment, whereas no differences were evident between the groups with regard to myocardial cytokine expression. AG-556 attenuated the decrease in fractional shortening at the expense of preserving end systolic diameter. AG-556 has proven beneficial in reducing myocardial infarct size and attenuated consequent hemodynamic deterioration in the rat model. If reconfirmed, AG-556 may be of potential clinical use in post-MI patients.

Animals↗