Apoptosis is related to imbalance of Th1/Th2-type cytokine in peripheral blood mononuclear cells of patients with chronic hepatitis B.

KEYWORDS: peripheral blood mononuclear cells; apoptosis; cytokine; hepatitis B virus.

Epoxyeicosatrienoic acids mediate adenosine-induced vasodilation in rat preglomerular microvessels (PGMV) via A2A receptors.

Activation of rat adenosine2A receptors (A2A R) dilates preglomerular microvessels (PGMV), an effect mediated by epoxyeicosatrienoic acids (EETs). Incubation of PGMV with a selective A2A R agonist, 2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 100 microM), increased isolated PGMV EET levels to 7.57+/-1.53 ng mg-1 protein from 1.06+/-0.22 ng mg-1 protein in controls (P<0.05), without affecting hydroxyeicosatetraenoic acid (HETE) levels (10.8+/-0.69 vs 11.02+/-0.74 ng mg-1 protein). CGS 21680-stimulated EETs was abolished by preincubation with an A2A R antagonist, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385) (100 microM). A selective epoxygenase inhibitor, methylsulfonyl-propargyloxyphenylhexanamide (MS-PPOH; 12 microM) prevented CGS 21680-induced increase in EETs, indicating inhibition of de novo synthesis of EETs. In pressurized (80 mmHg) renal arcuate arteries (110-130 microm) preconstricted with phenylephrine (20 nM), superfusion with CGS 21680 (0.01-10 microM) increased the internal diameter (i.d.) concentration-dependently; vasodilation was independent of nitric oxide and cyclooxygenase activity. CGS 21680 (10 microM) increased i.d. by 32+/-6 microm; vasodilation was prevented by inhibition of EET synthesis with MS-PPOH. Addition of 3 nM 5,6-EET, 8,9-EET and 11,12-EET increased i.d. by 53+/-9, 17+/-4 and 53+/-5 microm, respectively, whereas 14,15-EET was inactive. The responses to 5,6-EET were, however, significantly inhibited by indomethacin. We conclude that 11,12-EET is the likely mediator of A2A R-induced dilation of rat PGMV. Activation of A2A R coupled to de novo EET stimulation may represent an important mechanism in regulating preglomerular microvascular tone. British Journal of Pharmacology (2004) 141, 441-448. doi:10.1038/sj.bjp.0705640

Regulation of preglomerular microvascular 20-hydroxyeicosatetraenoic acid levels by salt depletion.

BACKGROUND: 20-hydroxyeicosatetraenoic acid (20-HETE) is the preeminent renal eicosanoid. The protean properties of 20-HETE - vasoactivity, mitogenicity and modulation of transport in key nephron segments - serve as the basis for the essential roles of 20-HETE in the regulation of the renal circulation and electrolyte excretion and as a second messenger for endothelin-1 (ET-1) and a mediator of selective renal effects of angiotensin II (AII). Renal autoregulation and tubular glomerular feedback are mediated by 20-HETE through constriction of preglomerular microvessels, particularly afferent arterioles. METHODS AND RESULTS: We had reported that rat preglomerular microvessels (PGMV; afferent-interlobular-arcuate/interlobular) in response to angiotensin II (AII) generate primarily 20-HETE and lesser quantities of 19-HETE. We have now addressed a possible link between the renin-angiotensin-system (RAS) and induction of cyclooxygenase (COX-2). As Na+ deprivation induces COX-2 expression/activity in the renal cortex and AII stimulates release of 20-HETE from PGMV, we used a stimulus, low dietary salt, to activate the RAS and COX-2 and thereby explore potential interactions involving 20-HETE and COX-2. CONCLUSIONS: The capacity of COX to metabolize 20-HETE to prostaglandin analogs e.g., 20-OH PGF2a and 20-OH PGE2, may be critical to modifying the renal vascular and tubular actions of the eicosanoids.

The cytotoxic principles of Solanum incanum.

In continuation of work on Solanum incanum a new steroidal alkaloid glycoside has been isolated from the fresh berries, which is named incanumine, and characterized as O(3)-[beta-D-xylopyranosyl-(1----3glu)-[beta-D-xylopyranosyl-(1--- -4rha)- alpha-L-rhamnopyranosyl-(1----4)]-beta-D-glucopyranosyl)-solasodine++ +. Solamargine, solasodine, ursolic acid, and ursolic acid derivatives (3-O-palmitoyl ursolic acid, 3-O-crotonyl ursolic acid, 3-O-propionyl ursolic acid) exhibited significant cytotoxic effects against human PLC/PRF/5 cells in vitro. Esterification of ursolic acid with aliphatic acids clearly enhanced the cytotoxic effects against human PLC/PRF/5 cells in vitro.

Photoradiation therapy: current status and applications in the treatment of brain tumors.

Photoradiation therapy is achieved when a photosensitizing drug is activated by light to form products that are lethal to tumor cells. The most commonly used drug is hematoporphyrin derivative, which is preferentially taken up and retained by malignant tissue. Photoactivation is usually produced by using a dye laser tuned at 630 nm (red light). The primary mechanism of neoplastic cell damage in photoradiation therapy involves the production of free radicals formed during illumination of hematoporphyrin derivative by light of this wavelength. The treatment would seem to damage first the tumor cell membrane, then the cytoplasmic inclusions, and finally the nucleus. Photoradiation therapy has been quite effective in the treatment of superficial malignancies, especially in skin, breast, eye, bladder, bronchus, and stomach. Experience with brain tumors is still limited. Important unresolved problems in the application of photoradiation therapy to gliomas include relative uptake of hematoporphyrin derivative into the tumor, limited light penetration of the tissue, local heating, and damage induced in normal brain by photoradiation therapy.

Penetration of hematoporphyrin derivative into rat brain and intracerebral 9L glioma tissue.

Brain and glioma tissue levels of tritiated hematoporphyrin derivative (3H-HPD) were measured in normal and 9L intracerebral glioma-bearing rats at 24 hours following administration of 3H-HPD 2-20 mg/kg and at 24-120 hours after 3H-HPD 10 mg/kg. Levels of 3H-HPD in blood, liver, spleen and muscle were also measured. Tissue levels of 3H-HPD increased progressively as the dose was increased. In animals given 10 mg/kg, gradual decreases in tissue levels occurred between 24 and 72 hours but thereafter remained stable. The 3H-HPD level in gliomas was consistently 2-3 X greater than in brain tissue, despite changes in dosage and time interval. High levels of activity were measured in normal brain tissue at all dosage levels, and subsequent clearance of the 3H-HPD from brain, glioma, and other tissues was slow; at 120 hours after administration of 10 mg/kg, approximately 50% of the 24 hour level was still present. These results indicate that although a dose- and time-independent preferential uptake of hematoporphyrin derivative occurs in intracerebral gliomas, persistent high levels may be present in the surrounding brain. The disadvantages of using hematoporphyrin derivative rather than its individual components in studies of HPD uptake and photosensitization in the brain are discussed.

Photoradiation therapy of 9L-gliosarcoma in rats: hematoporphyrin derivative (types I and II) followed by laser energy.

Suspensions of 9L-gliosarcoma cells were inoculated into the brain or flank of rats and photoradiation therapy (PRT) was applied to the resulting tumors. The PRT consisted of hematoporphyrin derivative (HpD), type I or II, followed by single-fiber laser energy 24, 48, or 72 h later. Necrotic foci in brain tumors were most numerous following laser exposure 24 h after HpD; they were more than twice as common, and with less damage to healthy tissue, after HpD II than after HpD I with the same laser dose. Neither lifespan nor the final weight of brain tumor was affected by the type of HpD or whether PRT was applied once or twice. In rats with flank tumor, multiple PRT (up to X 4) did not delay tumor growth; also, 11 of 12 PRT-treated flank tumors grew after implantation at various sites in healthy rats. We conclude that HpD II is a more effective photosensitizer than HpD I. However, the value of PRT will be limited until a lethal dose of laser energy can be delivered throughout a tumor without destroying vital healthy tissue.

Effects of photoradiation therapy on normal rat brain.

Laser photoradiation of the brain via an optical fiber positioned 5 mm above a burr hole was performed after the injection of hematoporphyrin derivative (HpD) in 33 normal rats and 6 rats with an intracerebral glioma. Normal rats received HpD, 5 or 10 mg/kg of body weight, followed by laser exposure at various doses or were exposed to a fixed laser dose after the administration of HpD, 2.5 to 20 mg/kg. One control group received neither HpD nor laser energy, and another was exposed to laser energy only. The 6 rats bearing an intracranial 9L glioma were treated with HpD, 5 mg/kg, followed by laser exposure at various high doses. The temperature in the cortex or tumor was measured with a probe during laser exposure. The rats were killed 72 hours after photoradiation, and the extent of necrosis of cerebral tissue was measured microscopically. In the normal rats, the extent of brain damage correlated with increases in the dose of both the laser and the HpD. In all 6 glioma-bearing rats, the high laser doses produced some focal necrosis in the tumors but also damaged adjacent normal brain tissue. We conclude that damage to normal brain tissue may be a significant complication of high dose photoradiation therapy for intracranial tumors.

Neurological outcome correlated with spinal evoked potentials in a spinal cord ischemia model.

Occlusion of the abdominal aorta of the rabbit by inflating the balloon of a Swan-Ganz catheter positioned in the aorta is a simple and reliable method of producing spinal cord ischemia. The electrophysiological, neurological, and neuropathological correlates of ischemia with progressively longer durations and of ischemia after drug interventions were studied with the goal of developing an easily monitored, reproducible model for central nervous system ischemia. The percentage of animals developing paraplegia after varying periods of ischemia was zero after 15 minutes, 30% after 17 minutes, 33% after 20 minutes, 38% after 25 minutes, and 100% after 60 minutes of ischemia. After 25 minutes of ischemia the percentage of animals developing paraplegia was 87% when they were awake and not ventilated during ischemia and reperfusion, but dropped to 38% in animals that were paralyzed, sedated with ketamine, and ventilated, and when the metabolic acidosis that follows aortic occlusion was corrected during reperfusion. Pretreatment with thiopental, hypothermia, naloxone, methylprednisolone, and verapamil changed the percentage of animals developing paraplegia after 25 minutes of ischemia to 0%, 0%, 25%, 40%, and 100%, respectively. The component waves of the spinal somatosensory evoked potential (SSEP) disappeared sequentially during ischemia in the following order: P2, N4, N3, N2, and N1. After reperfusion, the SSEP components returned in reverse order of their disappearance. In the untreated animals, absence of the N3 wave for more than 10 minutes during ischemia was always followed by a neurological deficit. Pretreatment with thiopental or hypothermia permitted longer periods of electrophysiological silence without permanent neurological deficit. The ratio of the amplitude of N3 to N1 (N3/N1) was at least 70% of the control level, and N4 and P2 amplitudes were at least 30% of the control level at 120 minutes after reperfusion in all animals that had a normal outcome. Return of the N3/N1 amplitude to at least 90% of the control level or return of N3/N1 to 70% to 89% of control and P2 to at least 60% of control at 120 minutes after reperfusion reliably correlated with a normal 48-hour motor examination in animals with and without drug interventions.

A review of cerebrovascular surgery in the People's Republic of China.

Cerebrovascular disease (CBVD) is very common in the People's Republic of China (PRC). In 8 of 12 large cities in the PRC, CBVD ranked first in frequency as a cause of death. The ratio fo aneurysms to arteriovenous malformations (AVMs) was 0.84-2:1, much lower than in the United States (6.5:1). Hypertensive intracerebral hemorrhage (HIH) is the commonest cause of mortality in patients with CBVD; patients with ischemic stroke have been submitted to the extracranial-intracranial (EC-IC) arterial anastomosis since 1976. Moyamoya syndrome is not uncommon in the PRC; leptospiral arteritis was one of the major causes in the series that have been reported.

Brain tumors in the People's Republic of China: a statistical review.

This review analyzes 12,785 cases of pathologically confirmed brain tumors from three published subseries in the People's Republic of China (PRC). No major differences among these series (from different geographical locations) were found. The incidence of glioma was lower in the PRC than in the West, but higher than in Japan; the incidence of meningioma in the PRC was close to that reported from Japan, but lower than that in the West. In the PRC, neurinomas and pituitary adenomas were more frequent than in the West or Japan, and dysembryoplastic tumors seemed to be much more common than in the West or Japan. Metastasis of breast carcinoma to the brain was rare in the PRC. According to a statistical study of 4,059 cases, there were more brain tumors in males than in females (ratio, 1.7:1). Children compose 19% of the series, and elderly patients (over 55 years old) constitute 2.8%.

Spinal cord tumors in the People's Republic of China: a statistical review.

This paper summarizes data on 1639 pathologically confirmed spinal cord tumors described in three reports published in the People's Republic of China (PRC). The average ratio of brain to spinal cord tumors in these studies was 8:1. The ratio of neurinomas to meningiomas was 3.8:1; this value is much higher than those found in western reports (almost 1:1), but is close to the ratio reported in the Japanese literature (3.9:1). Eleven per cent of the spinal cord tumors in the PRC were dysembryoplastic. In children, the percentage was 52.7%, one of the highest values reported in the world literature. Meningioma was the only type of spinal cord tumor that occurred more frequently in females than in males (2.5:1). Children (under 16 years old) had 19% and elderly patients (over 60 years old) had 2.6% of the spinal cord tumors in the PRC.