Activation of the Akt/GSK3beta signaling pathway mediates survival of vulnerable hippocampal neurons after transient global cerebral ischemia in rats.

Recent studies have revealed that the phosphatidylinositol 3-kinase (PI3-K) pathway is involved in apoptotic cell death after experimental cerebral ischemia. The serine-threonine kinase, Akt, functions in the PI3-K pathway and prevents apoptosis by phosphorylation at Ser473 after a variety of cell death stimuli. After phosphorylation, activated Akt inactivates other apoptogenic factors, including glycogen synthase kinase-3beta (GSK3beta), thereby inhibiting cell death. However, the role of Akt/GSK3beta signaling in the delayed death of hippocampal neurons in the CA1 subregion after transient global cerebral ischemia (tGCI) has not been clarified. Transient global cerebral ischemia for 5 mins was induced by bilateral common carotid artery occlusion combined with hypotension. Western blot analysis showed a significant increase in phospho-Akt (Ser473) and phospho-GSK3beta (Ser9) in the hippocampal CA1 subregion after tGCI. Immunohistochemistry showed that expression of phospho-Akt (Ser473) and phospho-GSK3beta (Ser9) was markedly increased in the vulnerable CA1 subregion, but not in the ischemic-tolerant CA3 subregion. Double staining with phospho-GSK3beta (Ser9) and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed different cellular distributions in the CA1 subregion 3 days after tGCI. Phosphorylation of Akt and GSK3beta was prevented by LY294002, a PI3-K inhibitor, which facilitated subsequent DNA fragmentation 3 days after tGCI. Moreover, transgenic rats that overexpress copper/zinc-superoxide dismutase, which is known to be neuroprotective against delayed hippocampal CA1 injury after tGCI, had enhanced and persistent phosphorylation of both Akt and GSK3beta after tGCI. These findings suggest that activation of the Akt/GSK3beta signaling pathway may mediate survival of vulnerable hippocampal CA1 neurons after tGCI.     

Angiotensin I-converting enzyme inhibitor improves reactive hyperemia in elderly hypertensives with arteriosclerosis obliterans.

Endothelial function in elderly hypertensive patients with arteriosclerosis obliterans has not been evaluated. We examined whether antihypertensive drugs improve vasodilatory response to reactive hyperemia of the limbs in elderly hypertensive patients (83 +/- 8 [SD] years) without (n=46, 0.9 < or = ankle-brachial pressure index < or = 1.4) and with (n=24) arteriosclerosis obliterans (ankle-brachial pressure index < 0.2). Patients were randomized for treatment with monotherapy of either temocapril (14 with and 26 without arteriosclerosis obliterans) or amlodipine (10 with and 20 without arteriosclerosis obliterans) for 6 months. Blood flows of the forearms and legs were measured by strain-gauge plethysmography. The vasodilatory response to the release of compression of the forearms and thighs at 200 mmHg or 20 mmHg more than systolic blood pressure for 5 min and to sublingual administration of nitroglycerin (0.3 mg) was assessed. The maximum reactive hyperemic flow in 35 legs with arteriosclerosis obliterans was significantly (p < 0.001) decreased compared to the value in legs in the control hypertensive subjects. Moreover, maximum reactive hyperemic flow in the forearms of patients with arteriosclerosis obliterans was significantly (p = 0.002) decreased compared to that in the control subjects. Blood pressure was similarly decreased by treatment with temocapril or amlodipine. Response to nitroglycerin (0.3 mg) was not changed by either drug. Treatment with temocapril significantly improved maximum reactive hyperemic flow of not only the legs and forearms in control hypertensives but also the legs and forearms in patients with arteriosclerosis obliterans, and attenuated the worsening of activity of daily living in these patients, although treatment with amlodipine did not. These results suggest that the angiotensin-converting enzyme inhibitor temocapril has a beneficial effect on endothelial function in elderly patients with arteriosclerosis obliterans.     

Pemphigus Vulgaris Associated with Autoimmune Hemolytic Anemia and Elevated TNFα

A 76-year-old female was admitted with many bullae and erythema on her trunk and extremities. A biopsy specimen showed significant intercellular edema in the lower epidermis and eosinophilic infiltration into the dermis and the epidermis. Immunofluorescent staining revealed the deposition of IgG in the intercellular area of her prickle cells. From these histologic findings and the typical clinical features, we diagnosed her as having pemphigus vulgaris. Examination of her blood revealed that she also suffered from autoimmune hemolytic anemia. Despite intensive treatment with prednisolone, she finally died. This case is of interest because of its rarity and the TNFα detected significantly in the blister fluid of this patient.     

An experimental study on direct revascularization of bronchial circulation by microvascular anastomosis.

The effects of direct revascularization of the bronchial artery after bronchoplasty were estimated by laser Doppler velocimetry and india ink injection in dogs. Bronchoplastic surgery at the right main bronchus was performed in all dogs, and the bronchial artery was reconstructed using the internal thoracic artery in the reconstruction group. The mucosal blood flow was measured at the distal side of the anastomosis. India ink was injected into the aorta in the nonreconstruction group and into the internal thoracic artery in the reconstruction group. The peripheral blood flow had diminished immediately after surgeries to 59% of the baseline value and took 14 days to recover to the baseline value in the nonreconstruction group. However, in the reconstruction group, the blood flow recovered at once to 78% of the baseline value and had returned to that value in 5 days. Statistically significant differences were noted between the groups from just after operation to day 7. India ink data confirmed these findings. In the nonreconstruction group, no ink was observed in the peripheral bronchial vessels on day 3; it was noted in part of the vessels on day 7 and in most on day 14. On the other hand, a relatively large number of vessels were stained just after operation in the reconstruction group. Thus reconstruction of the bronchial artery by means of the anastomosis with the internal thoracic artery can be said to be a useful and effective method for preventing airway ischemia.     

Estimating neuron dendritic length in 3D from total vertical projections and from vertical slices

The recently developed method of total vertical projections is illustrated to estimate the total dendritic length of a human Substantia Nigra neuron. Next, the length of the different orders of dendritic branches, and the mean segment length for each order - commonly regarded as important parameters in neuron physiology - are also estimated. Finally, it is shown how to estimate the mean dendritic length in a population of neurons from vertical slices of arbitrary and unknown thickness. Being unbiased and highly efficient, the proposed methods offer interesting alternatives to current procedures used for the metric analysis of neuron arborizations.     

The effect of nilvadipine on bloodflow in the dorsal pedis artery in type 2 diabetic patients--a study using duplex Doppler ultrasonography.

The effects of nilvadipine on the peripheral circulation in the lower extremities using a duplex system of two-dimensional colour and pulse Doppler ultrasonography were studied in 32 patients with type 2 diabetes mellitus and mild essential hypertension. The patients (19 men and 13 women) were randomly divided into treatment and control groups. The anatomical cross-sectional area and blood flow index of the dorsal pedis artery were determined by colour and pulse Doppler ultrasonography before and 60 min after administration of 4 mg nilvadipine or placebo. Pulse rate and blood pressure were measured simultaneously. There were no significant changes in pulse rate or blood pressure after administration of either drug. Both cross-sectional areas (from 4.3 +/- 0.4 to 5.2 +/- 0.5 mm2, p < 0.05) and blood flow index (from 40.3 +/- 4.3 to 58.8 +/- 9.0, p < 0.05) were significantly increased in the treatment group, whereas there were no significant changes in either measurement in the control group. The findings showed that a single administration of nilvadipine increases blood flow in the dorsal pedis arteries of diabetic patients.     

Thrombopoietin in postoperative thrombocytopenia following living donor hepatectomy.

Thrombocytopenia is a frequent finding following living donor hepatectomy. It appears more pronounced in right graft donors than in left graft donors. This study analyzed postoperative thrombocytopenia in 20 living liver donors and examined the change of endogenous thrombopoietin (TPO) in its recovery. Platelet count, TPO level, fibrinogen degradation product (FDP), and D-Dimer were measured before surgery and on postoperative days (PODs) 1, 2, 3, 5, 7, and 14. Concurrently, liver and spleen volumes were calculated by computed tomography. Platelet count on POD 3 was significantly lower in right graft donors than in left graft donors (13.0 +/- 3.7 x 10(4)/microL vs. 16.8 +/- 4.0 x 10(4)/microL, P = 0.039) but recovered by POD 7 in all donors. Postoperative elevations of FDP and D-Dimer were significantly higher in right graft donors than in left graft donors. TPO level rose immediately after surgery, peaked on POD 5 in left graft donors and on POD 7 in right graft donors, and fell nearly to preoperative levels by POD 14. Postoperative TPO level per liver volume was significantly higher in right graft donors than in left graft donors. In conclusion, thrombocytopenia following living donor hepatectomy resolved within the first week regardless of graft type and was mainly associated with increasing consumption of circulating platelets, possibly due to intrahepatic and splenic congestion. With a reduced number of circulating platelets, TPO level rapidly increases. Also, with reduced consumption of platelets related to recovery from surgery, thrombocytopenia should resolve. As a consequence, TPO level would be expected to fall.     

Intraocular kinetics of ceftazidime (Modacin).

The concentration of ceftazidime was determined in the aqueous humor and the vitreous body of normal, vitrectomized and aphakic/vitrectomized eyes and in the serum of albino rabbits 1 h after intravenous injection of 100 mg/kg ceftazidime. The intravitreal ceftazidime concentration was low (0.1-0.2 microgram/ml) in normal eyes 1 h after intravenous injection, and high (8.7 +/- 8.5 micrograms/ml) in vitrectomized and aphakic/vitrectomized eyes when injected immediately after surgery. The ceftazidime concentration was also determined in the aqueous humor and the vitreous body of normal eyes and in the serum of albino rabbits 3, 6, 12, 24 and 48 h after intravitreal injection of 200 micrograms. The intravitreal ceftazidime concentration after intravitreal injection decreased exponentially for 12 h (half-life about 7.4 h). It decreased more slowly thereafter and remained at 13.0 micrograms/ml (mean) even 48 h after injection. This concentration exceeded the minimum inhibitory concentrations against common gram-positive and gram-negative organisms causing endophthalmitis.