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At least 757 records · Page 42Linked to original sources
PubMed2000

[Bcl-2 antisense oligodeoxyribonucleotide increases apoptosis of lung carcinoma cells induced by cisplatin].

OBJECTIVE: To study the effect of antisense oligodeoxyribonucleotide (ODN) to apoptotic suppress gene bcl-2 on apoptosis of lung carcinoma cells induced by cisplatin. METHODS: The lung carcinoma cells expressing bcl-2 were chosen to participate in this experiment. Cultured cells were divided into 7 groups: ODN, nonsense, ODN + cisplatin, nonsense + cisplatin, cisplatin, lipofectin and control. Bcl-2 antisense or nonsense mixed with lipofectin was added into above corresponding cultured cells. After cultured for 6 hours, cisplatin was added into corresponding groups. The cells were cultured again for 16 hours. And then, the cells were smeared on slides. Apoptotic cells were labeled with TdT-mediated dUTP nick end labeling (TUNEL) method on cell smears. Apoptotic index (AI) was counted to show the percentage of apoptotic cancer cells. The immunocytochemistry was used to detect the expression of bcl-2 in carcinoma cells. RESULTS: The bcl-2 expression of cancer cell in ODN group was significantly decreased compared to the control and nonsense groups. The AI of ODN + cisplatin group was 16.4 +/- 1.7, cisplatin group 4.1 +/- 0.8, antisense group 5.9 +/- 0.2, nonsense group 3.3 +/- 0.7, nonsense + cisplatin 7.6 +/- 1.1, lipofectin 5.1 +/- 0.9, control group 3.6 +/- 0.6. The AI of antisense + cisplatin group was significantly higher than that of other groups. CONCLUSION: Antisense oligodeoxyribonucleotide to bcl-2 can inhibit significantly the expression of bcl-2 of lung cancer cells and increase apoptosis of cancer cells induced by cisplatin.

Antineoplastic Agents↗
PubMed2001

Ultraviolet a radiation suppresses an established immune response: implications for sunscreen design.

The ultraviolet radiation present in sunlight is the primary cause of nonmelanoma skin cancer and has been implicated in the development of cutaneous malignant melanoma. In addition, ultraviolet is immune suppressive and the suppression induced by ultraviolet radiation has been identified as a risk factor for skin cancer induction. Ultraviolet also suppresses the immune response to infectious agents. In most experimental models, ultraviolet is applied to immunologically naive animals prior to immunization. Of equal concern, however, is the ability of sunlight to suppress established immune reactions, such as the recall reaction in humans, which protects against microbial infections. Here we demonstrate that solar-simulated ultraviolet radiation, applied after immunization, suppresses immunologic memory and the elicitation of delayed-type hypersensitivity. Further, we found that wavelengths in the ultraviolet A region of the solar spectrum were critical for inducing immune suppression. Ultraviolet A (320-400 nm) radiation was as effective as solar-simulated ultraviolet A + B (290-400 nm) in suppressing the elicitation of an established immune response. Irradiation with ultraviolet AI (340-400 nm) had no effect. Supporting a critical role for ultraviolet A in ultraviolet-induced immune suppression was the observation that applying a sunscreen that contained an ultraviolet B only filter had no protective effect, whereas, a sunscreen containing both ultraviolet A and ultraviolet B filters totally blocked ultraviolet-induced immune suppression. These data suggest that sunlight may depress the protective effect of prior vaccination. In addition, the observation that ultraviolet A is immunosuppressive indicates the need for ultraviolet A protection when designing sun protection strategies.

Animals↗
PubMed2004

Aromatase inhibitors in the adjuvant setting: bringing the gold to a standard?

The death rate from breast cancer is falling rapidly in most developed countries due, at least in part, to the use of adjuvant endocrine therapy in women with endocrine responsive disease. In post-menopausal women tamoxifen has been the gold standard for nearly 20 years. More recently the aromatase inhibitors (AI) have become established in the management of advanced breast cancer and are being evaluated in the adjuvant setting in trials that include tens of thousands of women. Recently, data have emerged that provide increasingly strong evidence supporting the use of AI in the adjuvant setting. Anastrozole as initial adjuvant endocrine treatment has shown superiority over tamoxifen in terms of disease free survival, and impressive reductions in the risk of recurrence have been demonstrated in trials evaluating the switch from tamoxifen to an AI, either letrozole after 5 or exemestane after 2-3 years of tamoxifen respectively. The data from these recent publications, and the potential impact on routine care of women with post-menopausal breast cancer is discussed.

Aged↗
PubMed2000

Association between blood pressure reduction with antihypertensive treatment and sleep apnea activity.

This study investigated whether a drug therapy-induced reduction in nocturnal blood pressure (BP) was associated with decreased sleep apnea activity. Two polysomnographies from 54 hospitalized male hypertensive, obstructive sleep apnea patients were analyzed in a double-blind, randomized, parallel-group trial of the angiotensin-converting enzyme inhibitor cilazapril (C), 2.5 mg once daily, or placebo (P). Blood pressure was measured by means of an intra-arterial catheter. Compared with P, C lowered mean arterial BP during non-rapid eye movement (NREM) (-8.3 +/- 10.7 mm Hg, P = .05) and REM sleep (-8.6 +/- 10.1 mm Hg, P = .02). Respiratory disturbance index (-8.6 +/- 3.2 events/h of sleep (n/h), P = .01) and apnea index (AI) (-6.6 +/- 3.0 n/h, P = .04) during NREM sleep were lowered by C and, to a lesser extent, by P (-5.9 +/- 3.2 n/h, P = .07 and -5.0 +/- 3.6 n/h, P = .18, respectively). The effect on AI and hypopnea index (HI) during REM sleep was not significant for C (-5.9 +/- 3.4 and 0.1 +/- 2.0, NS, respectively) and P (-2.6 +/- 3.9 and 1.6 +/- 2.0, NS, respectively). There was a significant linear correlation between the change in REM systolic BP and the change in REM AI (r = 0.28, P = .04); the mean BP change correlated negatively with the change in HI (-0.28, P = .04). During NREM sleep there was no significant correlation between changes in BP and the treatment effects on sleep apnea activity. Blood pressure reduction after short-term antihypertensive treatment did not affect sleep disordered breathing during NREM sleep. Reduced BP was associated with a weak reduction of AI and a slight increase of HI during REM sleep. It appears that elevated BP contributes only marginally to sleep apnea severity in hypertensive patients with obstructive sleep apnea.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Induction of bile acid synthesis by cholesterol and cholestyramine feeding is unimpaired in mice deficient in apolipoprotein AI.

High density lipoprotein (HDL) cholesterol is believed to be preferentially utilized for bile acid synthesis and biliary secretion. In mice, the deletion of apolipoprotein AI (apo AI), the major apolipoprotein in HDL, results in very low plasma HDL-cholesterol levels. This article describes bile acid metabolism in apo AI-deficient (Apo AI(-/-)) mice and their C57BL/6 (Apo AI(+/+)) controls fed either a basal rodent diet alone or containing cholesterol or cholestyramine. Basal plasma HDL-cholesterol levels in the (-/-) mice (<10 mg/dL) were less than 20% of those in their (+/+) controls, but there were no phenotypic differences in either the relative cholesterol content of gallbladder bile, bile acid pool size and composition, fecal bile acid excretion or the activity of, or mRNA level for, cholesterol 7alpha-hydroxylase. However, compared with their (+/+) controls, the (-/-) mice absorbed more cholesterol (33 vs. 24%) and manifested lower rates of hepatic sterol synthesis (534 vs. 1,019 nmol/h per g). Cholesterol feeding increased hepatic cholesterol levels in the (+/+) animals from 2.7 to 4.4 mg/g and in the (-/-) mice from 2.6 to 8.1 mg/g. Bile acid synthesis increased 70% in both genotypes. Cholestyramine feeding stimulated bile acid synthesis 3.7 fold in both (-/-) and (+/+) mice. We conclude that the virtual loss of HDL-cholesterol from the circulation in apo AI deficiency has no impact on the ability of the hepatocyte to adapt its rate of bile acid synthesis in concert with the amount of cholesterol and bile acid returning to the liver from the small intestine.

Animals↗
PubMed2000

Anti-inflammatory effects of a stabilized lipid extract of Perna canaliculus (Lyprinol).

A lipid-rich extract, prepared by supercritical fluid (CO2) extraction of freeze-dried stabilized NZ green-lipped mussel powder (Lyprinol) has shown significant anti-inflammatory (AI) activity when given to animals and humans. When treated p.o. with Lyprinol, Wistar and Dark Agouti rats developed neither adjuvant-induced polyarthritis or collagen(II)-induced auto-allergic arthritis. This was achieved with doses < NSAIDs, and 200 times < of other seed or fish oils. Lyprinol subfractions inhibited LTB4 biosynthesis by PMN in vitro, and PGE2 production by activated macrophages. Much of this AI activity was associated with omega-3 PUFAs and natural antioxidants [e.g. carotenoids]. In contrast to NSAIDs, Lyprinol is non-gastro toxic in disease-stressed rats at 300 mg/kg p.o., and does not affect platelet aggregation [human, rat]. Clinical studies, either controlled or randomized, have demonstrated very significant AI activity in patients with osteoarthritis (OA), rheumatoid arthritis (RA), asthma, and other inflammatory conditions. Lyprinol is a reproducible, stable source of bioactive lipids with much greater potency than plant/marine oils currently used as nutritional supplements to ameliorate signs of inflammation.

Animals↗
PubMed2003

The growth inhibitory effect of p21 adenovirus on androgen-dependent and -independent human prostate cancer cells.

OBJECTIVE: To assess the potential of p21 as a gene therapy treatment for prostate cancer, by introducing p21 into both androgen-dependent (AD) and -independent (AI) human prostate cancer cell lines via a recombinant adenoviral vector, Ad5CMV-p21, carrying human p21 cDNA. MATERIALS AND METHODS: The LNCaP, DU145 and PC-3 human prostate cancer cell lines were cultured and infected with Ad5CMV-p21. Cell growth, cell-cycle progression and tumorigenicity were then assessed by thymidine incorporation into cellular DNA, and cell number, flow cytometry, and tumour growth after inoculating the cells into nude mice. RESULTS: Growth was inhibited in Ad5CMV-p21 viral-infected AD and AI prostate cancer cells. The effects were dose-dependent, regardless of the androgen status of the cell lines. Flow cytometric analysis showed that Ad5CMV-p21 arrested cell-cycle progression at G1/S with no appreciable effect on the levels of apoptotic cells. The tumorigenicity of cancer cells infected with Ad5CMV-p21 was greatly reduced in athymic mice. CONCLUSIONS: These results suggest that Ad5CMV-p21 may be a new therapeutic agent for human prostate cancer gene therapy.

Adenoviridae↗
PubMed2002

Increased plasma C-reactive protein in familial hypoalphalipoproteinemia: a proinflammatory condition?

BACKGROUND: HDL molecules have an established role in the regression processes of atherosclerosis as well as a putative role as antiinflammatory agents. Our study investigated whether familial hypoalphalipoproteinemia, a genetic form of dyslipidemia characterized by very low HDL levels, might be associated with increased inflammation markers such as C-reactive protein. METHODS AND RESULTS: A total of 50 subjects with hypoalphalipoproteinemia (age, 53.1+/-16.7 years) were compared with 64 healthy controls (age, 51.9+/-12.4 years). Apart from significantly lower values of HDL cholesterol (30.2+/-4.0 versus 52.5+/-12.7 mg/dL, P<0.0001) and apolipoprotein AI (113.3+/-20.0 versus 155.4+/-24.9 mg/dL, P<0.0001) and higher levels of triglycerides (141.3+/-62.9 versus 73.5+/-39.9 mg/dL, P<0.0001), patients did not show different plasma values of total cholesterol and LDL cholesterol when compared with healthy controls (181.5+/-36.6 versus 186.3+/-32.6 mg/dL; 123.0+/-31.5 versus 119.1+/-30.3 mg/dL). CRP plasma values were significantly higher in patients than in controls (median 0.34 [range 0.02 to 4.66] versus 0.07 [0.02 to 0.85] mg/dL, P<0.0001). In the patient group, CRP values were significantly higher in subjects with angiographically documented coronary atherosclerotic disease than in those without. Moreover, CRP concentrations were inversely correlated with both HDL cholesterol (r= -0.44, P=0.0006) and apolipoprotein AI (r= -0.45, P=0.0006) values. CONCLUSIONS: Elevation of C-reactive protein values in familial hypoalphalipoproteinemia, in the absence of signs and symptoms of local or systemic inflammation or systemic or recurrent disease, may suggest an upregulation of proinflammatory mechanisms, which is further exacerbated by the presence of coronary atherosclerotic disease.

Adult↗
PubMed1992

Effect of pravastatin on serum lipids, apolipoproteins and lipoprotein (a) in patients with non-insulin dependent diabetes mellitus.

In 43 patients with non-insulin dependent diabetes mellitus (NIDDM) associated with hypercholesterolemia, the effect of pravastatin, a potent HMG CoA-reductase inhibitor, on serum lipids, apolipoproteins and lipoprotein (a) was examined. After 1 to 3 months administration of 10 mg per day of pravastatin, the serum levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) were significantly decreased, while the serum level of high density lipoprotein cholesterol (HDL-C) was significantly increased in patients with NIDDM. The levels of apolipoproteins B (apo B) and E were significantly decreased, while apolipoprotein AI (apo A-I) was not changed by the administration of pravastatin. The atherogenic indices (LDL-C/HDL-C and apo B/apo A-I) were significantly decreased by the administration of this drug. The serum lipoprotein (a), which was increased in the diabetic patients, was not affected by the pravastatin treatment. Plasma glucose and hemoglobin A1c levels were not affected by the treatment. We concluded that pravastatin is a potentially useful agent in the treatment of hypercholesterolemia in patients with NIDDM.

Apolipoproteins↗
PubMed2006

Microbiology, safety, and pharmacokinetics of aztreonam lysinate for inhalation in patients with cystic fibrosis.

BACKGROUND: Aztreonam lysinate for inhalation (AI) is a novel monobactam formulation being investigated for pulmonary Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF). METHODS: Pre-clinical studies investigated the pre- and post-nebulization activity of AI and its activity in the presence of CF sputum. A double-blind, placebo-controlled, dose-escalation trial determined pharmacokinetics and tolerability of AI in subjects with CF. Single daily escalating doses of AI 75, 150, or 225 mg, or placebo were self-administered using an eFlow Electronic Nebulizer. Sputum samples were collected up to 4 hr and blood samples up to 8 hr post-dose. RESULTS: AI activity against multiple CF isolates was retained after nebulization via eFlow, and activity was not inhibited by CF sputum. All 12 adult subjects and 11/12 adolescents tolerated all AI doses. One patient had an asymptomatic FEV1 decrease > 20% with the 150 mg dose. Median aztreonam sputum concentrations in adults 10 min after AI 75, 150, and 225 mg were 383, 879, and 985 microg/g, respectively. Median sputum concentrations in adolescents 10 min after AI 75, 150, and 225 mg were 324, 387, and 260 microg/g, respectively. Systemic exposure to AI was low. Plasma pharmacokinetics in adults receiving AI 75 mg were Cmax = 419 ng/g, Tmax = 0.99 hr, t1/2 = 2.1 hr. Aztreonam concentrations in sputum were at or above the MIC50 for at least 4 hr post-dose. CONCLUSION: These data support the continued development of AI for treatment of pulmonary infections in patients with CF.

Administration, Inhalation↗
PubMed2003

Unique induction of p21(WAF1/CIP1)expression by vinorelbine in androgen-independent prostate cancer cells.

To study the mechanisms of the development of hormone refractory prostate cancer, we established an androgen-independent (AI) prostate cancer cell line derived from hormone-dependent (AD) LNCaP cells. Our previous studies have demonstrated that AI cells are deficient in expression of p21(WAFl/CIP1) (p21) due to overexpressed AR and are resistant to apoptosis. In this study, the induction of p53 and p21 expression by vinorelbine (Navelbine) was compared between AD and AI cells in an attempt to understand the difference(s) in apoptotic signalling pathways in these cells. Using a series of deletion of p21 reporter constructs, we found that vinorelbine mediated p21 induction in a p53-dependent manner in AD cells. In contrast, p21 expression restored by vinorelbine in AI cells was found to be through both p53-dependent and-independent pathways. In the absence of two p53 binding sites, Spl-3 and Spl-4 sites, in the promoter of human p21 gene, were found to be required for vinorelbine-mediated p21 activation. No p21 induction was observed by paclitaxel in AI cells. Exposure of AI cells to paciltaxel followed by vinorelbine produced synergism. Our data, thus, provide a basis for the synergistic combination of vinorelbine and paclitaxel for the treatment of advanced prostate cancer.

Androgen Antagonists↗
PubMed2004

Preclinical evaluation of a prostate-targeted gene-directed enzyme prodrug therapy delivered by ovine atadenovirus.

Gene-directed enzyme prodrug therapy (GDEPT) based on the Escherichia coli enzyme, purine nucleoside phosphorylase (PNP), provides a novel strategy for treating slowly growing tumors like prostate cancer (CaP). PNP converts systemically administered prodrug, fludarabine phosphate, to a toxic metabolite, 2-fluoroadenine, that kills PNP-expressing and nearby cells by inhibiting DNA, RNA and protein synthesis. Reporter gene expression directed by a hybrid prostate-directed promoter and enhancer, PSMEPb, was assayed after plasmid transfection or viral transduction of prostate and non-CaP cell lines. Androgen-sensitive (AS) LNCaP-LN3 and androgen-independent (AI) PC3 human CaP xenografts in nude mice were injected intratumorally with an ovine atadenovirus vector, OAdV623, that carries the PNP gene under PSMEPb, formulated with cationic lipid for enhanced infectivity. Fludarabine phosphate was then given intraperitoneally for 5 days at 75 mg/m2/day. PNP expression was evaluated by enzymic conversion of its substrate using reverse phase HPLC. OAdV623 showed excellent in vitro transcriptional specificity for CaP cells. In vivo, expression of PNP persisted for > 6 days after OAdV623 injection and a single treatment provided 100% increase in tumor doubling time and > 50% inhibition of tumor growth for both LNCaP-LN3 and PC3 lines, with increased tumor necrosis and apoptosis and decreased tumor cell proliferation. OAdV623 significantly suppressed the growth of AS and AI human CaP xenografts in mice.

Adenine↗
PubMed2005

Pharmacologic augmentation of high-density lipoproteins: mechanisms of currently available and emerging therapies.

PURPOSE OF REVIEW: With the limited effects of low-density lipoprotein-based lipid intervention, more attention is being paid to drugs that augment or mimic high-density lipoprotein's beneficial effects. A thorough understanding of the anti-atherogenic effects of high-density lipoprotein, and the mechanisms of existing or emerging high-density lipoprotein-based therapies, is essential for rational strategy for the prevention of cardiovascular disease. RECENT FINDINGS: High-density lipoprotein mediates its beneficial effects through reverse cholesterol transport and direct anti-inflammatory effects of apolipoprotein AI and other component parts. Currently available drugs increase high-density lipoprotein-C through increasing apoAI synthesis (statins, fibrates) and decreasing apolipoprotein AI catabolism (niacin). Cholesteryl ester transfer protein inhibitors dramatically raise high-density lipoprotein-C, but clinical data are still required to verify their cardioprotective effects. Novel therapies such as apolipoprotein AImilano, apolipoprotein AI mimetic peptide, and exogenous phospholipids show tremendous promise as treatments for atherosclerosis. SUMMARY: High-density lipoprotein and its defining functional protein apoAI prevent atherosclerosis through reverse cholesterol transport and other direct effects. Research has led to the development of novel therapies that increase high-density lipoprotein-C or that mimic direct anti-atherogenic effects of apolipoprotein AI. As these emerging therapies find a place in clinical medicine, we can anticipate preventing a much higher degree of cardiovascular events.

Amides↗
PubMed1999

Safety of air medical transportation after tissue plasminogen activator administration in acute ischemic stroke.

BACKGROUND AND PURPOSE: We sought to determine the safety of air medical transport (AMT) of patients with acute ischemic stroke (AIS) immediately after or during administration of tissue plasminogen activator (tPA). Patients with AIS treated with tPA in nonuniversity hospitals frequently need transfer to tertiary care centers that can provide specialized care. AMT is a widely available mode of transport that is crucial in providing expedient and quality health care to critically ill patients while assuring high level of care during transportation. The safety of AMT of patients with AIS after or during administration of tPA has not been examined. METHODS: We performed retrospective chart review of 24 patients with AIS who were treated with intravenous tPA and transferred by helicopter to the Hospital of the University of Pennsylvania or the University of Cincinnati Hospital. The charts were reviewed for neurological complications, systemic complications, and adherence to the National Institutes of Neurological Disorders and Stroke (NINDS) protocol for AIS management. RESULTS: No major neurological or systemic complications occurred. Four patients had hypertension warranting treatment, 3 patients experienced motion sickness, 1 patient developed a transient confusional state, and 1 patient experienced minor systemic bleeding. Four NINDS protocol violations occurred, all related to blood pressure management. CONCLUSIONS: In this small series, AMT of AIS patients after thrombolysis was not associated with any major neurological or systemic complications. Flight crew education on the NINDS AIS protocol is essential in limiting the number of protocol violations. AMT of patients with AIS provides fast and safe access to tertiary centers that can provide state of the art stroke therapy.

Acute Disease↗
PubMed1999

Postoperative hypotension after carotid angioplasty and stenting: report of three cases

OBJECTIVE AND IMPORTANCE: Hemodynamic instability after carotid angioplasty and stenting is not well recognized. We report three patients who developed sustained hypotension in the postoperative period after successful carotid angioplasty and stent placement for internal carotid artery stenosis in the carotid sinus region. CLINICAL PRESENTATION: In two patients, hypotension was initially induced by inflation of the angioplasty balloon. The third patient developed hypotension after completion of the procedure. In all cases, the hypotension persisted for 18 to 33 hours after the procedure. During the postoperative period, two of these patients also developed sinus bradycardia, which, in one patient, was further complicated by a third-degree atrioventricular block. INTERVENTION: The hypotension was successfully treated by intravenous vasopressors or inotropic agents. No permanent neurological or cardiac sequelae were observed. CONCLUSION: Sustained hypotension with or without bradycardia may develop after carotid angioplasty and stent placement, presumably as a result of carotid sinus dysfunction. During the postoperative period, patients should be monitored in settings suited to expeditious management of cardiovascular emergencies.

Journal Article↗
PubMed2000

Evidence for neuronal dysfunction in migraine: concurrence between specific qEEG findings and clinical drug response--a retrospective analysis-.

OBJECTIVE: The aim of this analysis was to verify objective correlates of the clinical improvement of migraine in patients by means of quantitative topographical EEG (qEEG). METHODS: Overall 40 migraine-outpatients participated in this retrospective analysis of prophylactic migraine treatment over 3-8 months with 1600 to 2000 mg cyclandelate daily. In all patients qEEG was recorded and analysed using the Fast Fourier Transformation and the determination of the Abberation Index (AI = the statistical probability of belonging to a qEEG reference group of healthy people, n = 500). RESULTS: A clinical response (> 50% reduction of migraine attack frequency and duration) was observed in 77.5% (n = 31). The number and duration of migraine attacks per month (median values) were reduced in a highly significant manner. In this observation 75% of all patients investigated showed a pathological positive Aberration Index at a single electrode or a cluster of neighbouring brain sites. This consisted in a power increase in theta, alpha and/or beta1 activity, and 73.3% of them had also a corresponding negative AI-focus (power decrease). In 15 patients EEG aberrations (positive AI clusters) within one frequency band were found, whereas 15 patients showed aberrations in more than one frequency. Positive AI s were mainly found in fronto-temporal and occipital brain areas with one single topographical difference between the patients with and without aura. CONCLUSIONS: Positive AI values were the main electrophysiological findings in these migraine patients. This was supported by the highly significant decrease of the median amount of the positive AI after clinically successful treatment with cyclandelate. Twenty four out of thirty patients with positive AI foci showed concurrence between qEEG-changes and clinical response. Patients with positive AI foci involving the lower or middle frequencies (theta and/or alpha 1) seemed to show a better clinical response (84.6%) than those with AI foci with participation of only faster frequencies (alpha 2 and/or beta 1; 54.5%). A controlled study is needed to confirm these observations.

Adolescent↗
PubMed1982

A comparison of inhibition of angiotensin I conversion by three converting enzyme inhibitors in rats.

1. The pressor responses to angiotensin I (AI) were suppressed in a dose related manner by the three converting enzyme inhibitors (CEI); SA 446, SQ 14 225 and MK 421. 2. The inhibitory action of SA 446 and SQ 14 225 was rapid in onset and decayed with time, while that of MK 421 was slower in onset and maintained for the 1 h of observation. 3. A single oral administration of MK 421 (80 mumol/kg) significantly decreased the pressor effect of AI 24 h later. In contrast, neither SA 446 nor SQ 14 225 reduced the AI-induced response at this time. 4. In anaesthetized genetically hypertensive rats, the depressor effect of MK 421 was greater than that of either SA 446 or SQ 14 225.

3-Mercaptopropionic Acid↗
PubMed2006

Thalidomide suppresses melanoma growth by activating natural killer cells in mice.

Although thalidomide (Thd) is being extensively investigated for its effects on cytokine production and T cell costimulation, it is poorly understood whether it is capable of modulating the activities of natural killer (NK) cells. In this study, Thd effects on NK cell activity were examined with a murine model of melanoma, which is mostly rejected by NK cell-dependent mechanism. Administration of Thd significantly (p<0.01 on Day 21) suppressed the growth of subcutaneous B16F1 melanoma. In Thd-treated mice, marked splenomegaly and augmented splenocyte count were observed. Additionally, the percentage of splenic NK1.1+ cells was elevated to approximately 2.5-fold within 10 days after Thd treatment. The expression of interferon inducible protein (IP)-10, interferon (IFN)-gamma, interleukin (IL)-12 and IL-18 was remarkably upregulated. Production of the cytotoxic molecule perforin was also augmented. These data suggest that Thd strongly activates NK cell activity in mice, possibly resulting in enhanced tumor surveillance defense.

Actins↗