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Biomedical subjects

M Talan

Publications and source records attributed to M Talan.

8 recordsLinked to original sources

Adenovirus-mediated VEGF(121) gene transfer stimulates angiogenesis in normoperfused skeletal muscle and preserves tissue perfusion after induction of ischemia.

BACKGROUND: Administration of angiogenic factors stimulates neovascularization in ischemic tissues. However, there is no evidence that angiogenesis can be induced in normoperfused skeletal muscles. We tested the hypothesis that adenovirus-mediated intramuscular (IM) gene transfer of the 121-amino-acid form of vascular endothelial growth factor (AdCMV.VEGF(121)) could stimulate neovascularization in nonischemic skeletal muscle and consequently attenuate the hemodynamic deficit secondary to surgically induced ischemia. METHODS AND RESULTS: Rabbits and rats received IM injections of AdCMV.VEGF(121), AdCMV.Null, or saline in the thigh, 4 weeks (rabbits) or 2 weeks (rats) before femoral artery removal in the injected limb. In unoperated rats, at the site of injection of AdCMV.VEGF(121), we found 96% and 29% increases in length density of arterioles and capillaries, respectively. Increased tissue perfusion (TP) to the ischemic limb in the AdCMV.VEGF(121) group was documented, as early as day 1 after surgery, by improved blood flow to the ischemic gastrocnemius muscle measured by radioactive microspheres (AdCMV.VEGF(121)=5.69+/-0.40, AdCMV.Null=2.97+/-0.50, and saline=2.78+/-0.43 mL x min(-1) x 100 g(-1), P<0.001), more angiographically recognizable collateral vessels (angioscore) (AdCMV. VEGF(121)=50.58+/-1.48, AdCMV.Null=29.08+/-4.22, saline=11.83+/-1.90, P<0.0001), and improvement of the bioenergetic reserve of the gastrocnemius muscle as assessed by (31)P NMR spectroscopy. Follow-up studies showed that superior TP to the ischemic limb in the AdCMV.VEGF(121) group persisted until it was equalized by spontaneous collateral vessel development in untreated animals. CONCLUSIONS: IM administration of AdCMV.VEGF(121) stimulates angiogenesis in normoperfused skeletal muscles, and the newly formed vessels preserve TP after induction of ischemia.

Adenoviridae↗

Induction of angiogenesis by cationic lipid-mediated VEGF165 gene transfer in the rabbit ischemic hindlimb model.

PURPOSE: The purpose of this study was to test the efficacy of a new cationic lipid formulation coupled with the cDNA encoding for the 165-residue form of vascular endothelial growth factor (VEGF(165)) to induce neovascularization and enhance blood flow in the rabbit ischemic hindlimb model. METHODS: Two days after removal of their right femoral arteries, rabbits received intramuscular injections of different concentrations of VEGF(165) or saline solution in the ischemic thigh. Tissue perfusion and increased neovascularization of the ischemic limb were assessed weekly on the basis of the calf blood pressure ratio for the ischemic/nonischemic limbs, regional blood flow to the skeletal muscles as measured with radioactive microspheres, postmortem angiography, and histology. RESULTS: At weeks 1 and 2 after surgery, animals treated with 1000 microgram of VEGF(165) had a 1.5-fold increase and a 2.5-fold increase, respectively, in the regional blood flow to both the adductor and gastrocnemius muscles of the ischemic limb. The blood pressure ratio was also greater in the treated animals than in the controls at weeks 2 and 3 after surgery. Early neovascularization in the VEGF(165) group was further documented at week 1 after surgery by more angiographically recognizable collateral vessels (angioscores were 64.13 +/- 2.51 and 38.28 +/- 3.82 for VEGF(165) and saline solution, respectively; P <.001) and by a threefold increase in the number of capillaries (vascular density) relative to the controls (P <.005). CONCLUSIONS: Intramuscular administration of a single dose of plasmid-liposomes encoding for VEGF(165) accelerates angiogenesis and increases blood flow in the rabbit hindlimb ischemic model. Therefore, this nonviral vector could be recommended for further testing for use in therapeutic angiogenesis.

Animals↗

Vascular permeability effect of adenovirus-mediated vascular endothelial growth factor gene transfer to the rabbit and rat skeletal muscle.

OBJECTIVE: Vascular endothelial growth factor has been used in preclinical studies and phase 1 and 2 clinical trials as a potent mediator of therapeutic angiogenesis; however, its ability to enhance the vascular permeability may be a source of potential complications. The objective of this work was to evaluate the effects of the intramuscular injection of an adenovirus vector coding for the 121-amino acid form of vascular endothelial growth factor (Ad.VEGF(121 )) on vascular permeability and edema development in rabbits and rats. METHODS: Different concentrations of Ad.VEGF(121 ) ranging from 10(5) to 10(10) plaque-forming units/mL (3 x 10(6)-3 x 10(11) particles/mL) were injected into hind limb or forelimb muscles of Wistar rats or rabbits. The size of the scrotum, the circumferences of limbs, and the concentration of vascular endothelial growth factor in the serum were measured daily after injection. RESULTS: The injection of different concentrations of Ad.VEGF(121 ) into the hind limb muscles of rabbits led to a dose-dependent scrotal edema in rabbits at concentrations higher than 10(7) plaque-forming units/mL (P =.002). The edema developed slowly, reached its maximum level 6 days after the injection, and spontaneously resolved thereafter. At concentrations higher than 10(9) plaque-forming units/mL the scrotal edema was accompanied by skin necrosis (P =.0001). No scrotal edema was observed in rats. CONCLUSIONS: The massive species-specific scrotal edema accompanied by skin ulceration and necrosis was observed only in rabbits treated with Ad.VEGF(121 ) in concentrations exceeding therapeutic doses. The therapeutic doses of Ad.VEGF(121 ) resulted in only moderate transient scrotal edema in rabbits, suggesting that the potential for side effects of vascular endothelial growth factor therapy as a result of increased vascular permeability should not be very alarming for generally healthy patients and may not cause a significant clinical problem in the treatment of peripheral vascular diseases.

Adenoviridae↗

Relationship of body temperature stability to mortality in aging mice.

An age-related decline in the capacity for thermoregulation among homeothermic animals has been observed frequently under conditions of extreme ambient temperatures. We investigated the temporal stability of the internal body temperature of 69 C57BL/6J mice from 25 months of age until death in a controlled, neutral thermal environment. Estimates of temporal variability were calculated over consecutive 1-month intervals using (colonic) body temperature data collected weekly. The results of this longitudinal analysis indicated that the regulation of body temperature, as measured by its temporal stability, became increasingly less precise with advancing age. Body temperature exhibited a significant decline as the animal approached death. Individual differences in body temperature and the temporal regulation of body temperature were significantly correlated with lifespan, although the direction of the relations were opposite. Body temperature correlated positively with lifespan, whereas the temporal stability of body temperature correlated negatively with lifespan. Thus, animals exhibiting higher body temperatures and greater temporal stability also tended to live longer than their cohorts.

Aging↗

An improved cold stress test for aging mice.

Tolerance to cold stress is a simple and reliable test which can be used longitudinally to study age-related differences or changes in thermoregulation of C57BL/6J mice. Neither prior food deprivation nor permanently inserted thermoprobes are necessary conditions for eliciting reliable age differences. However, restraint during the test is important and does elicit reliable age differences.

Aging↗

Body temperature of C57BL/6J mice with age.

On the basis of a study of rectal temperature in a group of 180, C57BL/6J male mice, ranging in age from 3 months to 30 months, the following conclusions were drawn: 1) The positive correlation between body weight and body temperature typical for rodents was found only for young adults of the C57BL/6J strain; 2) body temperature of male C57BL/6J did not appear to decline until about 23.5 months, after which there was a significant negative correlation (r = -0.53) between age and temperature.

Aging↗

Applying the performance improvement team concept to the medication order process.

Healthcare literature suggests that most adverse drug events (ADEs) are the results of errors at the prescribing stage. These ADEs affect patients, physicians, pharmacists, nurses, and hospital administrators. Improving systems and providing education, rather than tracking the performance of individual prescribers, seem to be more effective in preventing and reducing ADEs. Pharmacists' participation on patient medical rounds and their presence in a satellite pharmacy increased their accessibility and their ability to share pertinent clinical information and thereby improved the medication order process and, ultimately, patient care. The pharmacy and medicine departments at one hospital took a proactive multidisciplinary approach that resulted in streamlining the medication order process, decreasing delays in initiating drug therapy, preventing ADEs, enhancing the knowledge of healthcare professionals, meeting the needs and expectations of patients and providers, and employing cost-effective drug therapy.

Adverse Drug Reaction Reporting Systems↗