Serum vitamin D level correlates with disease activity and health-related quality of life in antineutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND AND OBJECTIVE: The association between vitamin D levels and disease activity has been established in patients with several autoimmune rheumatic diseases. We aimed to examine the association between vitamin D and disease activity of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: Fifty-four AAV patients and 50 age- and sex-matched healthy controls without vitamin D supplements were included. Clinical and laboratory data were evaluated during the assessment of vitamin D levels. Two different forms of vitamin D in the sera-25(OH)D, which is the sum of 25(OH)D2 and 25(OH)D3, and 25(OH)D3, which only includes 25(OH)D in its D3 form-were measured, and the relationship between vitamin D and the obtained data was assessed. Variations in vitamin D levels relative to the season were also evaluated. RESULTS: Patients with AAV demonstrated considerably lower 25(OH)D serum levels than healthy controls (16.0 vs. 20.4 ng/mL, p = 0.016), and the proportion of individuals with vitamin D deficiency was higher in patients with AAV than in healthy controls (68.5% vs. 48.0%, p = 0.035). Both serum 25(OH)D and 25(OH)D3 were positively associated with the 36-item Short-form Health Survey (SF-36) physical component summary and SF-36 mental component summary (MCS) scores. A negative correlation was observed between 25(OH)D and 25(OH)D3 serum levels and Birmingham vasculitis activity score (BVAS), C­reactive protein (CRP), and white blood cell count. Linear regression analysis indicated haemoglobin and 25(OH)D levels to be independently associated with BVAS and CRP and 25(OH)D levels with SF-36 MCS score. No seasonal variations were observed in vitamin D levels. CONCLUSION: The results from this study suggest that vitamin D levels could provide clinically useful information in AAV.

Omega-3 fatty acids supplementation on major cardiovascular outcomes: an umbrella review of meta-analyses of observational studies and randomized controlled trials.

OBJECTIVE: Omega-3 fatty acids are commonly used as a lipid-lowering agent or dietary supplement for the purpose of prevention of cardiovascular diseases. However, even large-scale clinical trials have not shown significant results demonstrating clear clinical benefits in cardiovascular diseases. Thus, this umbrella review aims to summarize and evaluate the evidence of clinical effects of omega-3 fatty acids supplementation on cardiovascular outcomes through comprehensive analyses of previous randomized controlled trials (RCTs) or observational cohort studies. MATERIALS AND METHODS: We conducted relevant publication search in PubMed, Embase, and Cochrane Database of Systematic Reviews. We retrieved and analyzed 3,298 articles published until August 28th, 2019. RESULTS: We identified 29 relevant articles and analyzed 83 meta-analyses of RCTs or cohort studies therefrom. As a result, we identified 12 cardiovascular outcomes that are related to omega-3 fatty acids supplementation. Among them, total mortality from major cardiovascular causes (RR 0.92, 95% CI 0.86 to 0.98) had significant inverse associations, and moreover, statistical significances were maintained even in subgroup analysis of large-scale RCTs including more than 1,000 patients (RR 0.94, 95% CI 0.88 to 0.99). CONCLUSIONS: Our umbrella review study shows that omega-3 fatty acids supplementation have a clinical benefit in reducing mortality from cardiovascular causes. However, many studies still have shown conflicting results, and therefore, further studies will be needed to verify the clinical benefit of omega-3 supplementation.

Onion (Allium cepa L.) peel extract (OPE) regulates human sperm motility via protein kinase C-mediated activation of the human voltage-gated proton channel.

Onion (Allium cepa L.) and quercetin protect against oxidative damage and have positive effects on multiple functional parameters of spermatozoa, including viability and motility. However, the associated underlying mechanisms of action have not yet been identified. The aim of this study was to investigate the effect of onion peel extract (OPE) on voltage-gated proton (Hv1) channels, which play a critical role in rapid proton extrusion. This process underlies a wide range of physiological processes, particularly male fertility. The whole-cell patch-clamp technique was used to record the changes in Hv1 currents in HEK293 cells transiently transfected with human Hv1 (HVCN1). The effects of OPE on human sperm motility were also analyzed. OPE significantly activated the outward-rectifying proton currents in a concentration-dependent manner, with an EC50 value of 30 µg/mL. This effect was largely reversible upon washout. Moreover, OPE induced an increase in the proton current amplitude and decreased the time constant of activation at 0 mV from 4.9 ± 1.7 to 0.6 ± 0.1 sec (n = 6). In the presence of OPE, the half-activation voltage (V1/2 ) shifted in the negative direction, from 20.1 ± 5.8 to 5.2 ± 8.7 mV (n = 6), but the slope was not significantly altered. The OPE-induced current was profoundly inhibited by 10 µm Zn2+ , the most potent Hv1 channel inhibitor, and was also inhibited by treatment with GF109203X, a specific protein kinase C (PKC) inhibitor. Furthermore, sperm motility was significantly increased in the OPE-treated groups. OPE exhibits protective effects on sperm motility, at least partially via regulation of the proton channel. Moreover, similar effects were exerted by quercetin, the major flavonoid in OPE. These results suggest OPE, which is rich in the potent Hv1 channel activator quercetin, as a possible new candidate treatment for human infertility.

Effects of eupatilin on the contractility of corpus cavernosal smooth muscle through nitric oxide-independent pathways.

Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is one of the main compounds present in Artemisia species. Eupatilin has both antioxidative and anti-inflammatory properties and a relaxation effect on vascular contraction regardless of endothelial function. We evaluated the relaxant effects of eupatilin on the corpus cavernosum (CC) of rabbits and the underlying mechanisms of its activity in human corpus cavernosum smooth muscle (CCSM) cells. Isolated rabbit CC strips were mounted in an organ bath system. A conventional whole-cell patch clamp technique was used to measure activation of calcium-sensitive K+ -channel currents in human CCSM cells. The relaxation effect of eupatilin was evaluated by cumulative addition (10-5  m ~ 3 × 10-4  m) to CC strips precontracted with 10-5  m phenylephrine. Western blotting analysis was performed to measure myosin phosphatase targeting subunit 1 (MYPT1) and protein kinase C-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17-kDa (CPI-17) expression and to evaluate the effect of eupatilin on the RhoA/Rho-kinase pathway. Eupatilin effectively relaxed the phenylephrine-induced tone in the rabbit CC strips in a concentration-dependent manner with an estimated EC50 value of 1.2 ± 1.6 × 10-4  m (n = 8, p < 0.05). Iberiotoxin and tetraethylammonium significantly reduced the relaxation effect (n = 8, p < 0.001 and p = 0.003, respectively). Removal of the endothelium or the presence of L-NAME or indomethacin did not affect the relaxation effect of eupatilin. In CCSM cells, the extracellular application of eupatilin 10-4  m significantly increased the outward currents, and the eupatilin-stimulated currents were significantly attenuated by treatment with 10-7  m iberiotoxin (n = 13, p < 0.05). Eupatilin reduced the phosphorylation level of MYPT1 at Thr853 of MLCP and CPI-17 at Thr38. Eupatilin-induced relaxation of the CCSM cells via NO-independent pathways. The relaxation effects of eupatilin on CCSM cells were partially due to activation of BKCa channels and inhibition of RhoA/Rho-kinase.

Sonographic evaluation of diaphragmatic function during breathing control.

OBJECTIVE: To investigate the effect of "breathing control" on sonographic diaphragmatic excursion. METHOD: A prospective, randomized, assessor-blinded study design involving 20 physiotherapy students; ten with knowledge of the breathing control technique (Group BC) and ten without (Group CON). All participants were asked to perform a Chester step test. Group BC performed BC, while Group CON adopted their own breathing pattern during recovery after the step test. Respiratory rate and sonographic parameters of the diaphragm including diaphragmatic excursion, speed of diaphragmatic contraction (slope of contraction), and inspiratory time were recorded before and after the step test. RESULTS: All baseline data were similar for both groups except age. Respiratory rate at 1 min post-step test was higher in Group CON (24.6±4.9 bpm) compared to Group BC (15.6 ± 3.8 bpm) (p < 0.001). Post-step test sonographic evaluation demonstrated an increase in diaphragmatic excursion with a significant time and group interaction (F(4,72) = 5.499, p = 0.005). Post hoc analysis revealed that the diaphragmatic excursion was significantly higher in Group BC compared to Group CON at first, second and third minute post-step test. Time and group interactions were not significant in inspiration time (F(4,72) = 2.459, p = 0.082) nor the slope of contraction (F(4,72) = 0.655, p = 0.582)]. CONCLUSION: Post-exercise diaphragmatic excursion was higher in participants applying BC. Non-invasive ultrasonography is able to promote objective evaluation of the relationship between breathing techniques and diaphragmatic function.

Additive effects of Artemisia capillaris extract and scopoletin on the relaxation of penile corpus cavernosum smooth muscle.

The objective was to investigate the cellular effect and action mechanism of Artemisia capillaris extract (ACE) and its component, scopoletin, on penile corpus cavernosum smooth muscle (PCCSM). In vitro study with PCCSM, the precontracted PCCSM with phenylephrine was treated with ACE or scopoletin. Cyclic nucleotides in the perfusate were measured by radioimmunoassay and expression of protein and mRNA of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase in the perfused PCCSM were measured by western blot and real-time PCR, respectively. The interaction of ACE or scopoletin with udenafil was also evaluated. ACE and scopoletin exerted a significant and concentration-dependent relaxation in PCCSM. The perfusion with ACE or scopoletin significantly increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) and the perfusion with ACE or scopoletin increased the expression of eNOS mRNA and protein. Furthermore, ACE or scopoletin enhanced udenafil-inducing relaxation in PCCSM. ACE and scopoletin relaxed the PCCSM mainly by activating nitric oxide-cGMP system and cAMP pathway and they may be additive therapeutic candidates for ED patients who do not completely respond to udenafil.

Assessment of fetal and neonatal outcomes in the offspring of women who had been treated with dried ginger (Zingiberis rhizoma siccus) for a variety of illnesses during pregnancy.

The present study was designed to investigate if exposure to dried ginger during pregnancy would increase the risk of adverse fetal and neonatal outcomes. Participants consisted of 159 singleton pregnant women who received dried ginger as a herbal medication. We also included a control group of 306 pregnant women who had not been exposed to any herbal medication or any known teratogen. No increased risk of major malformations was detected in exposed women (OR = 4.9; 95% CI 0.9-25.5; p = 0.051). The incidence of stillbirths in the exposed group was marginally higher than in the controls (OR = 7.8; 95% CI 0.9-70.3; p = 0.05). The risk was more evident when the exposed group was compared with the general population in the Republic of Korea (OR = 7.9; 95% CI 2.9-21.4; p < 0.0001). Other fetal and neonatal study outcomes investigated in the exposed group were similar (p > 0.05) to the controls. In conclusion, dried ginger does not appear to be a major teratogen. However, due to the limitations of the study, e.g. the large variability in the dose of dried ginger in the exposed group, as well as the concomitant exposure to other herbal medications, the increased incidence of stillbirths requires confirmation in larger cohort studies.

Experience of a specialist centre in the management of anastomotic sinus following leaks after low rectal or ileal pouch-anal anastomosis with diverting stoma.

AIM: The natural history and appropriate management of anastomotic sinus has not been clearly defined. The aim of this study was to evaluate the incidence, management and outcomes of anastomotic sinus. METHOD: The medical records of all patients who underwent a low anterior resection (LAR) or an ileal pouch-anal anastomosis (IPAA) with a diverting loop ileostomy (LI) and with contrast enema performed before planned stoma closure between 2001 and 2011 were retrospectively reviewed. The radiological features of the sinus tract, treatment and outcome of anastomotic sinus were studied. RESULTS: Twenty patients (8.2%) were found to have anastomotic sinuses out of the total of 244 patients who had undergone LAR (n = 146) or IPAA (n = 98) with LI. Of these, 13 (65%) had prior symptomatic leaks, while seven did not. Twelve patients (60%) were found to have simple sinus tracts, while eight had complex sinuses (associated with either pelvic cavities or severe strictures). Five patients with simple tracts were treated with observation alone. Fifteen patients underwent surgical interventions. Overall, with a median follow-up of 28 (6-73) months, 16 patients (80%) had resolution of their sinuses. All of 12 patients (100%) with simple sinus tracts and four of eight patients (50%) with complex sinuses underwent successful stoma reversals after 8 (3.5-24) months following the initial surgery (P = 0.01). CONCLUSION: Patients with simple tracts are significantly more likely to have complete resolution of sinuses than patients with complex sinuses. Persistent sinus associated with either a pelvic cavity or severe stricture despite surgical intervention is likely to lead to a permanent stoma.

Bortezomib attenuates murine collagen-induced arthritis.

OBJECTIVES: Nuclear factor kappa B (NF-kappaB) is a major regulator of pivotal proinflammatory cytokines in the pathogenesis of rheumatoid arthritis (RA). Bortezomib inhibits NF-kappaB activation by blocking the degradation of the NF-kappaB inhibitor, I-kappaB. In this study, the efficacy of bortezomib on murine collagen-induced arthritis (CIA) was investigated. METHODS: Thirty-five male DBA/1 mice were divided into five groups. All mice except controls were injected with type II collagen. Mice in the bortezomib-treated groups were injected intraperitoneally with 0.01, 0.1 and 1 mg/kg bortezomib twice a week for 2 weeks. Controls and mice in the untreated group were also injected intraperitoneally with phosphate-buffered saline in the same manner. Arthritis score and paw thickness were measured and histopathological assessment of joint sections was performed. The expression of proinflammatory cytokines and enzymes was evaluated by immunohistochemical staining. Joint destruction was confirmed using three-dimensional micro-computerised tomography (CT). Blood cells were counted and liver and kidney functions were monitored. RESULTS: Bortezomib significantly attenuated the severity of arthritis and histopathological findings in CIA mice. The expression of tumour necrosis factor alpha, IL-1beta, IL-6, matrix metalloproteinase 3, cyclooxygenase 2 and inducible nitric oxide synthase decreased in bortezomib-treated mice compared with untreated mice. In addition, micro-CT confirmed that bortezomib reduced joint destruction. No adverse effects in blood cells, liver or kidneys were observed with bortezomib treatment. CONCLUSIONS: These data suggest that bortezomib may play an anti-inflammatory role in the pathophysiology of RA and serve as a new therapeutic modality for RA.

Case report: spontaneous atriofascicular pathway automaticity simulating ventricular tachycardia.

Atriofascicular pathways most commonly present electrocardiographically as an antidromic reciprocating AV reentrant tachycardia. We report the case of a child who presented in infancy with a wide QRS complex tachycardia thought to be supraventricular tachycardia with aberrant conduction, associated with tachycardia-induced cardiomyopathy. Later in life the same patient represented with episodes of palpitations secondary to a wide QRS complex tachycardia, thought to be ventricular tachycardia. Electrophysiologic mapping demonstrated the origin of the wide QRS complex tachycardia was from automatic activity originating from a right anterolateral atriofascicular pathway, which also participated in a reentrant antidromic AV reciprocating tachycardia. Radiofrequency ablation of the atriofascicular pathway successfully eliminated both arrhythmias. The mechanism of the wide QRS complex tachycardia appeared to result from spontaneous automaticity of the atriofascicular pathway.

Suppression of tumor cell growth both in nude mice and in culture by n-3 polyunsaturated fatty acids: mediation through cyclooxygenase-independent pathways.

Dietary n-3 polyunsaturated fatty acids (PUFAs), as compared with n-6 PUFAs, suppress cellular production of prostaglandins and tumor cell growth both in vitro and in vivo. However, the mechanism by which n-3 PUFAs suppress tumor growth is not understood. We investigated whether the suppression of tumor cell growth by dietary n-3 PUFAs is mediated through inhibition of cyclooxygenase (COX). A colon tumor cell line, HCT-116, that does not express COX was stably transfected with the constitutively expressed COX-1 or the inducible COX-2 cDNA using a retroviral transfection and infection system. Athymic nude mice transplanted with the cells expressing enzymatically active COX were fed isocaloric diets containing either safflower oil or fish oil for 2 weeks before the start of the experiment and for an additional 21 days after transplantation. Both tumor volume and tumor burden (tumor volume/body weight) were significantly reduced in mice fed the fish oil diet as compared with safflower oil-fed mice. This reduction occurred even in control mice that received injections with cells infected with the retroviral vector without COX-1 or COX-2 cDNA. The growth of tumor cells expressing COX was not different from the growth of those transfected with the vector alone in the nude mice and in soft agar. N-3 PUFAs, as compared with linoleic acid, also inhibited the growth of these cells in culture. This growth inhibition by n-3 PUFAs was not affected by COX-1 or COX-2 overexpression. Contrary to general belief, these results indicate that the suppression of tumor growth by dietary n-3 PUFAs is mediated through COX-independent pathways.

Neoadjuvant chemotherapy and radiation for inoperable carcinoma of the maxillary antrum: a matched-control study.

A matched-control study comparing standard radiotherapy versus neoadjuvant chemotherapy and radiation was undertaken to clarify the effects of neoadjuvant systemic chemotherapy for locally advanced squamous cell carcinoma of the maxillary antrum. Thirty-four patients with inoperable maxillary cancer were treated with neoadjuvant chemotherapy and radiotherapy (Group II). Before starting radiotherapy, all patients in Group II received two or three cycles of neoadjuvant chemotherapy consisting of cisplatin and a 5-day continuous infusion of 5-fluorouracil with or without intravenous injection of vinblastine. Radiation doses ranged from 66 Gy to 75 Gy (median, 70 Gy). The response rate, patterns of failure, toxicity, and survival for Group II were compared with those for 34 stage-matched patients treated with radiation alone (Group I). Despite a higher response rate to neoadjuvant chemotherapy, the recurrence rate and patterns of treatment failure were not influenced by the addition of neoadjuvant chemotherapy. In most cases, neoadjuvant chemotherapy did not interfere with subsequent radiotherapy, and radiation-induced late complications occurred equally in both treatment groups. After a median follow-up of 48 months, there was no significant difference in 5-year actuarial survival or disease-free survival between the two treatment groups. Radiation alone for inoperable maxillary cancer was clearly suboptimal for improving local control and survival rate, but neoadjuvant chemotherapy in addition to standard radiotherapy failed to demonstrate any therapeutic advantage over radiation alone.

Clinical features of 31 patients with systemic contact dermatitis due to the ingestion of Rhus (lacquer).

In Korea, Rhus has been used as a folk medicine to cure gastrointestinal diseases and as a health food. We review the clinicopathological and laboratory findings in patients with systemic contact dermatitis caused by intake of Rhus. We reviewed medical records and histopathological sections from 31 patients during a 10-year period. The male/female ratio was 1.4: 1 and the average age was 43.8 years (range 22-70). Ten patients (32%) had a known history of allergy to lacquer. Rhus was ingested to treat gastrointestinal problems including indigestion and gastritis (45%), and as a health food (39%), in cooked meat, in herbal medicine, or taken by inhalation. The patients developed skin lesions such as a maculopapular eruption (65%), erythema multiforme (EM, 32%), erythroderma (19%), pustules, purpura, weals and blisters. Erythroderma was very frequent in patients with a known history of allergy to lacquer, but maculopapular and EM-type eruptions were more frequently observed in those without a history of allergy. All patients experienced generalized or localized pruritus. Other symptoms included gastrointestinal problems (32%), fever (26%), chills and headache; many developed leucocytosis (70%) with neutrophilia (88%), while some showed toxic effects on liver and kidney. Fifty-nine per cent of patients observed cutaneous or general symptoms within a day after ingestion of Rhus. There was no difference in the time lag for symptoms to develop between patients allergic and not allergic to Rhus. All patients responded well to treatment with systemic steroids and antihistamines. Common histopathological findings were vascular dilatation, perivascular lymphohistiocytic infiltration, and extravasation of red blood cells in the upper dermis. Rhus lacquer should not be ingested in view of its highly allergic and toxic effects.

New naphthalenyl glycosides from the roots of Juglans mandshurica.

Three new glycosides, 1,4,8-trihydroxynaphthalene-1-O-D-glucopyranosyl-(1-->6)-beta-D- xylopyranoside (1), 1,4,8-trihydroxynaphthalene-1-O-beta-D-glucopyranosyl-(1-->6)-alph a-L- arabinopyranoside (2), 1-hydroxy-4-methoxynaphthalene-1-O-beta-D-glucopyranosyl-(1-->6)- alpha-L-rhamnopyranoside (3), were isolated from the roots of Juglans mandshurica and their structures were elucidated on the basis of spectroscopic studies.

A case of methemoglobinemia after ingestion of an aphrodisiac, later proven as dapsone.

Methemoglobin (MetHb) is an oxidation product of hemoglobin in which the sixth coordination position of ferric iron is bound to a water molecule or to a hydroxyl group. The most common cause of acquired MetHb-emia is accidental poisoning which usually is the result of ingestion of water containing nitrates or food containing nitrite, and sometimes the inhalation or ingestion of butyl or amyl nitrite used as an aphrodisiac. We herein report a case of MetHb-emia after ingestion of an aphrodisiac, later identified as dapsone by gas chromatograph/mass selective detector (GC/MSD). A 24-year old male was admitted due to cyanosis after ingestion of a drug purchased as an aphrodisiac. On arterial blood gas analysis, pH was 7.32, PaCO2 26.8 mmHg, PaO2 75.6 mmHg, and bicarbonate 13.9 mmol/L. Initial pulse oxymetry was 89%. With 3 liter of nasal oxygen supplement, oxygen saturation was increased to 90-92%, but cyanosis did not disappear. Despite continuous supplement of oxygen, cyanosis was not improved. On the fifth hospital day, MetHb was 24.9%. Methylene blue was administered (2 mg/kg intravenously) and the patient rapidly improved. We proved the composition of aphrodisiac as dapsone by the method of GC/MSD.

Pinusolide from the leaves of Biota orientalis as potent platelet activating factor antagonist.

We investigated the effect of a new PAF antagonist pinusolide, isolated from the leaves of Biota orientalis, on PAF-induced [3H]serotinin release from rabbit platelets, hypotension and vascular permeability. Pinusolide (IC50, about 5 x 10(-6) M) inhibited specifically [3H]serotinin release from rabbit platelets when stimulated with PAF (5 x 10(-8) M), but showed no effect when induced by ADP, collagen, and thrombin. It also inhibited PAF-induced hypotension in a dose-dependent manner in rats with no effect on the hypotension induced by acetylcholine, histamine and serotonin. The inhibitory effect of pinusolide on the PAF-induced vascular permeability is less specific than the induced hypotension. These results suggest that pinusolide may prove of therapeutic value in the treatment of hypotension and a molecular design of pinusolide analogues may provide the possibility of a new PAF specific antagonists.

High level accumulation of an aberrantly spliced human DHFR RNA species.

Cells transduced with either of two human DHFR minigenes express an RNA product which is considerably shorter than what would be predicted from the size of an unspliced transcript expressed from its DNA template. RNA blotting analysis has shown that this short transcript accumulated to exceedingly high levels which were comparable to the levels reached by the highly abundant endogenous actin mRNA, or MoMLV RNA expressed in chronically infected cells. RNA blotting, RNase mapping, primer extension, RT-PCR, and sequencing have shown that this highly expressed transcript, termed TBN, is a spliced RNA product which utilizes cryptic splice signals present in the normally spliced DHFR mRNA. Subcloning experiments have demonstrated that all the information required for the generation and high level accumulation of the TBN transcripts is encoded in the 1.6 kb DHFR DNA minigene. TBN transcripts were generated with comparable efficiency from DNA templates containing either the human ADA or the early SV40 promoters. Since neither the ADA nor the SV40 promoter are considered to be particularly "strong" promoters, this observation argues that initiation of transcription is not the rate limiting step in determining the amount of the TBN transcripts which accumulate in the cell. Insertion of a foreign sequence into the DHFR DNA minigene led to the expression and high level accumulation of a chimeric transcript, suggesting that the unusual properties of this expression system may be used for high level expression of foreign sequences. These observations offer new insights into the mechanisms which control the accumulation of translatable mRNA in the cell, and have potentially important implications for experiments involving optimization of gene expression for gene therapy applications.

Inhibitory effect of Korean mistletoe (Viscum album coloratum) extract on tumour angiogenesis and metastasis of haematogenous and non-haematogenous tumour cells in mice.

We examined the inhibitory effect of an aqueous extract (referred to as KM-110) from Viscum album coloratum, a Korean mistletoe, on tumour metastasis produced by highly metastatic murine tumour cells, B16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 lymphoma cells, using experimental and spontaneous metastasis models in syngeneic mice. In experimental metastasis of B16-BL6 and colon 26-M3.1 cells, intravenous (i.v.) administration of KM-110 (100 micrograms/mouse) 1 day after tumour inoculation significantly inhibited lung metastasis of both tumour cells. The administration of KM-110 also exhibited a therapeutic effect on liver and spleen metastasis of L5178Y-ML25 lymphoma cells. Furthermore, in spontaneous metastasis of B16-BL6 melanoma cells, multiple administration of KM-110 into tumour-bearing mice resulted in significant inhibition of lung metastasis by tumour cells, as well as the suppressive activity to the growth of primary tumour. In in vivo analysis for tumour-induced angiogenesis, the i.v. administration of KM-110 suppressed tumour growth and inhibited the number of blood vessels oriented towards the tumour mass. In a bioassay, the culture supernatant (KM-110-treated medium) of murine peritoneal macrophages that had been stimulated with KM-110 (1-10 micrograms/ml) for 30 min followed by 24 h incubation in fresh medium showed a strong tumour necrosis factor-alpha (TNF-alpha) activity. In addition, KM-110-treated medium significantly inhibited the growth of in vitro cultures of rat lung endothelial (RLE) cells. These results suggested that the extract of Korean mistletoe inhibits tumour metastasis caused by haematogenous as well as non-haematogenous tumour cells, and that its antimetastatic effect results from the suppression of tumour growth and the inhibition of tumour-induced angiogenesis by inducing TNF-alpha.

A case of rectal cancer with sternal metastasis as initial presentation.

Colorectal cancer with bone metastasis as initial manifestation is a very rare event. We have reported a case of rectal cancer presenting with sternal metastasis. A 30 year-old man was evaluated due to pain in the sternal area with a bulging mass. History and physical examination did not suggest any specific disease. A radionuclide bone scan revealed increased uptake in the sternal area, right 6th rib, and sacrum. Microscopic examination of a biopsy specimen from the sternum showed metastatic adenocarcinoma. A barium enema and CT scan of the pelvis suggested carcinoma of the upper rectum. Adenocarcinoma of the rectosigmoid junction area was demonstrated by colonoscopic examination with biopsy. He received palliative transverse colostomy for obstruction without further treatment.