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•A magnetically recoverable Pd(II) catalyst was prepared and fully characterized.•The reaction conditions were optimized through a Factorial Design.•The products were obtained with ...yields ranging from 71 to 96%.•The catalyst was easily recovered and reused for three times.
A magnetically recoverable catalyst Fe3O4@SiO2-AEAPTMS-Pd(II) was prepared, fully characterized and had its catalytic activity evaluated on the Suzuki cross-coupling reaction under microwave irradiation. The reaction conditions for the synthesis of biaryl compounds was optimized in two stages - an initial fractional design 24, in which the parameters reaction time, temperature, solvent and catalyst loading were evaluated, followed by a Doehlert design. The factorial design proved to be a viable approach for obtaining the optimal reaction conditions based on a relatively small number of experiments. Additionally, the biaryl derivatives synthesized by this method were obtained with good to excellent yields (71–96%) and the recovery and reuse of the palladium catalyst was also evaluated.
To test the hypothesis that presence of metalloproteases (MMPs), their inhibitors (TIMPs) and their substrate laminin-5 differs between the ischemic core and the surrounding tissue, we examined the ...impact of middle cerebral artery occlusion/reperfusion (MCA:O/R) on these molecules in different regions of the infarct. We also investigated the influence of hypothermia on the progression of the ischemic lesion and MMP activity. Brain sections from 64 Wistar rats subjected to MCA:O/R were examined by means of cytohistochemistry and zymography. The artery was occluded for 2 h followed by 3, 5, 8 and 12 h of reperfusion. Well characterized antibodies against laminin-5, MMPs and TIMP-2 were used. A total of 32 rats were treated with hypothermia. The presence of each antigen was related to the following regions of interest: ischemic core with BBB breakdown (I
c), surrounding ischemic tissue without BBB breakdown (I
r), and the contralateral non-ischemic region (N). Regions of interest were defined by MRI. The I
c increased over time at the cost of the I
r. BBB breakdown occurred early in the ischemic core and increased over time. Hypothermia reduced the BBB breakdown at all time points. A graded decreased presence of laminin-5 was observed with 16.5±3.7(N)>10±2.8(I
r)>4±1.4(I
c) immunopositive microvessels/mm
2 at 3 h of reperfusion. MMP-9 showed a reverse pattern with 0 (N)<4±0.8(I
r)<10±1.5(I
c) immunopositive microvessels/mm
2. Hypothermia decreased the MMP activity measured by zymography. Laminin-5 and MMP presence relate directly to the degree of postischemic injury. Hypothermia reduces the conversion from the I
r to ischemic core and the degree of BBB as well as MMP abundance.
Thrombolysis (T) is limited by reperfusion-associated injury and the short therapeutic window after stroke onset. The present study investigates whether hypothermia alone or in combination with ...thrombolysis has beneficial effects after experimental thromboembolic stroke. Wistar rats (
n = 60) were subjected to thromboembolic occlusion (TE) of the middle cerebral artery (MCA). Thrombolysis (T) was performed with intravenous recombinant tissue-plasminogen activator (rt-PA) 1 h (early T) or 3 h (late T) after TE. Hypothermia (Hy) was applied for 4 h at 33°C started 1 h after TE. Experimental groups included control (C), early thrombolysis (ET), late thrombolysis (LT), hypothermia (Hy), early thrombolysis plus hypothermia (ET+Hy), and late thrombolysis plus hypothermia (LT+Hy). Animals were investigated by MRI and silver infarct staining (SIS) to assess the cerebral infarct size. All animals of group Hy survived, in contrast to 40% in group C (
P < 0.05). ET+HY and LT+Hy showed a trend towards better survival as compared to ET and LT alone. PWI parameters were not significantly different between ET versus ET+HY and LT versus LT+Hy, but rt-PA administration led to improved cerebral perfusion in MRI. Significant differences in infarct volumes (T2/SIS) were found after 24 h in all treatment groups versus the control group (
P < 0.05). The lesion volume calculated from T2 was significantly smaller in ET (16% ± 5%), ET+Hy (10 ± 4%), and LT+Hy (20% ± 9%) after 5.5 h (10.8% ± 4.8%) versus C (42% ± 15%), (
P < 0.05).
These data indicate that hypothermia improves survival and decreases infarct volume. However, there were no significant differences between the use of rt-PA alone or in combination with hypothermia. Further studies are needed to confirm these effects, also several days after stroke onset.
Abstract Pleiotropic mechanisms beyond their cholesterol lowering effect of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statins such as pravastatin are known. We used a ...temporary middle cerebral artery occlusion (tMCAO) model in 114 Wistar rats to assess i) whether repeated injections of various doses of pravastatin (0.1, 0.5, 1 and 2 mg/kg) at 30 min, 6 h, 1, 2, 3, and 4 days after stroke onset are neuroprotective, ii) whether attenuation of striatal glutamate and interleukin-6 (IL-6) release is part of the neuroprotective mechanism, and iii) how local cerebral blood flow (CBF) is influenced by pravastatin both in the acute and late stage of ischemia. Animals were sacrificed 5 days after MCAO, infarct size was analyzed with 2,3,5-triphenyltetrazolium chloride (TTC) staining. As compared to saline (139 ± 14 mm3 , n = 11), higher doses of pravastatin beyond 0.1 mg/kg significantly reduced infarct size with the greatest effect obtained with 1 mg/kg (60 ± 14 mm3 , n = 11, P = 0.0004). Using cerebral microdialyis in this dose group, we demonstrated that striatal glutamate increase in the ischemic hemisphere was attenuated by pravastatin compared to placebo. Likewise, IL-6 release was diminished at 2 h, but not at 6 h after tMCAO. Improvement of local CBF by pravastatin was observed at day 5, but not at 5 h after tMCAO, thus representing a more long term effect of pravastatin. In conclusion, a relatively high dose of pravastatin administered repetitively after stroke onset improved neurological outcome through various cholesterol-independent mechanisms.
Transluminal angioplasty of venous stenoses in polytetrafluoroethylene vascular access grafts. Since 1984, percutaneous transluminal angioplasty (PTA) utilizing high pressure balloon catheters has ...been used as an initial approach to restore patency of PTFE (polytetrafluoroethylene, GORE-TEX) hemodialysis vascular access grafts. Seventeen stenotic lesions detected by fistulogram underwent elective PTA. Twelve of these lesions were detected after thrombectomy and five were detected because of increased venous pressures during dialysis. Fourteen attempts at PTA were completely successful in restoring functional patency to the vascular graft. Three attempts were unsuccessful; two of these three grafts were subsequently repaired surgically. Venous stenoses that extended for greater than 6 cm were not considered for PTA. We conclude that PTA is a technique of promise in the non-surgical salvage of failing PTFE grafts. PTA can prolong the useful life of PTFE vascular access grafts and can be performed on an outpatient basis, eliminating the hospitalization that is usually required for surgical revision.
The effective delivery of dialysis requires repeated reliable access to the central circulation capable of providing rapid blood flow. This access to the circulation continues to be the 'weak link' ...in the provision of long-term renal replacement therapy. Dialysis access malfunction is a major cause of inadequate dialysis delivery and venous stenosis is the leading cause of access malfunction and thrombosis. Careful monitoring of venous dialysis pressures and recirculation along with urea kinetic modeling and physical examination of the graft can prospectively identify the malfunctioning vascular access. When these indicators are used for referral for fistulogram, venous stenosis can be identified and corrected before graft thrombosis. Not only can preemptive repair of the vascular access prevent thrombosis, it also allows for more efficient dialysis delivery to the patient.
Insulin-like growth factor (IGF) treatment has been shown to have trophic and neuroprotective effects in vitro and in vivo in different lesion models. IGF-I has potent neuroprotective effects after ...hypoxic-ischemic injury and global ischemia. The role of IGF-I in focal cerebral ischemia is only partially understood. Therefore, in the present study, we evaluated, by applying MRI monitoring, whether a clinically relevant systemic administration of IGF-I can achieve a long-lasting neuroprotective effect.
Male Wistar rats underwent transient occlusion of the right middle cerebral artery for 1 hour by using the suture occlusion model. Animals then were intraventricularly treated with 33.33 microg IGF-I/d for 3 days (group A, the IGF-I group n=13; group B, the placebo group n=14) or subcutaneously treated with 200 microg IGF-I/d for 7 days (group D, the IGF-I group n=10; group E, the placebo group n=10). Groups C and F served as sham-operated controls (n=5 and n=3, respectively). Treatment was begun 30 minutes after occlusion of the middle cerebral artery. Subcutaneously treated animals underwent MRI studies (diffusion-weighted imaging, perfusion imaging, and T2-weighted imaging) beginning 60 minutes after vessel occlusion at 6 hours and at days 1, 2, 5, and 7 after ischemia. The animals were weighed and neurologically assessed daily (rating scale ranged from 0, indicating no deficit, to 5, indicating death). On the third day (intraventricular trial) and on the seventh day (subcutaneous trial), animals were euthanized, and brain sections were stained with triphenyltetrazolium chloride.
The mean infarct volume was 52.9+/-25.2 mm(3) in intraventricularly treated animals versus 146.4+/-62.2 mm(3) in control animals (P<0.01) and 42.2+/-17.9 mm(3) in subcutaneously IGF-I-treated animals versus 73.1+/-38.1 mm(3) in control animals (P<0.05). Apparent diffusion coefficient-derived lesion volume at 60 minutes after occlusion was 40.4+/-23.7 mm(3) versus 38.3+/-19.3 mm(3) (P=NS), increased to 168.3+/-49.55 mm(3) versus 105.5+/-33.8 mm(3) (P<0.05) at 24 hours, and then decreased to 55.8+/-30.3 mm(3) versus 23.3+/-20.2 mm(3) (P<0.05) for control and IGF-I-treated animals, respectively. The T2-weighted-derived ischemic lesion volume at 24 hours after occlusion was 236+/-49.2 mm(3) versus 115.9+/-56.8 mm(3) (P<0.05) and decreased to 115.9+/-26.2 mm(3) versus 75.7+/-35.8 mm(3) (P<0.05) at day 7 for control and IGF-I-treated animals, respectively. The relative regional cerebral blood volume was reduced to 50% before reperfusion in all regions of interest except for region of interest 1 (vessel territory of anterior cerebral artery), recovered during reperfusion, but was not different between the control and the growth factor-treated group at any imaging time point. There was no significant difference in weight loss. There was less neurological deficit after ischemia in intraventricularly and subcutaneously IGF-I-treated animals compared with control animals (P<0.05).
Continuous treatment with intraventricularly and subcutaneously administered IGF-I achieved a long-lasting neuroprotective effect as early as 24 hours after ischemia as measured by MRI. Therefore, IGF-I may represent a new approach to the treatment of focal cerebral ischemia.
To investigate the effect of a reduced-fat diet and a monoene-enriched diet (MUFA diet) on serum lipids, glucose and insulin metabolism in subjects with elevated cholesterol and triglyceride ...concentrations.
Eighteen subjects with elevated serum cholesterol and triglyceride concentrations consumed the MUFA diet (39% of energy (E%) as fat and 21 E% monoenes) and the reduced-fat diet (34 E% fat, 16 E% monoenes) for 4 weeks according to a randomized cross-over design. Both periods were preceded by consumption of a standardized baseline diet for 2 weeks. Serum lipid and lipoprotein concentrations were determined at the beginning and end of each diet period. A frequently sampled intravenous glucose tolerance test was performed after the MUFA diet and the reduced-fat diet. Insulin sensitivity index (SI) was 40% higher after the reduced-fat diet than after the MUFA diet (2.42 +/- 0.42 vs 1.73 +/- 0.24 10(-4) min-1 U-1 ml-1, p = 0.018). This change in insulin sensitivity was seen in 13 subjects and was most evident in those who began with the MUFA diet. Compared to the baseline diet (high in saturated fat), both experimental diets lowered serum total and LDL cholesterol concentrations (6.6-6.9%, p < 0.05 and 7.4-8.0%, p < 0.05 respectively).
Both diets were equally effective in lowering serum lipid concentrations, but the reduced-fat diet resulted in better insulin sensitivity.
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