Association between blood omega-3 polyunsaturated fatty acids and the gut microbiota among breast cancer survivors.

Omega-3 polyunsaturated fatty acids (PUFAs) are essential nutrients demonstrated to have health benefits, such as decreasing the risk of coronary heart disease, improving parameters associated with metabolic syndrome, and decreasing anxiety symptoms and depression risk. Previous intervention studies indicated the association between blood or tissue PUFA levels and the gut microbiota; however, the details remain incompletely elucidated. We conducted a cross-sectional study to examine the association between PUFAs and the gut microbiota among breast cancer survivors. Adults who had been diagnosed with invasive breast cancer more than one year ago and were not currently undergoing chemotherapy were enrolled. Capillary blood and faecal samples were obtained to assess the blood PUFA levels and gut microbiota compositions. The mean age (n=124) was 58.7 years, and 46% of the participants had a history of chemotherapy. Multiple regression analysis controlling for possible confounders indicated that an increased relative abundance of Actinobacteria was significantly associated with increased levels of docosahexaenoic acid (DHA, beta=0.304, q<0.01). At the genus level, the abundance of Bifidobacterium was positively associated with the level of DHA (beta=0.307, q<0.01). No significant association between omega-6 PUFAs and the relative abundances of gut microbiota members was observed. In addition, analyses stratified by the history of chemotherapy indicated significant associations of PUFA levels with the abundance of some bacterial taxa, including the phylum Actinobacteria (DHA, beta=0.365, q<0.01) and Bacteroidetes (EPA, beta=-0.339, q<0.01) and the genus Bifidobacterium (DHA, beta=0.368, q<0.01) only among participants without a history of chemotherapy. These findings provide the first evidence of positive associations between the abundances of Bifidobacterium among the gut microbiota and the levels of omega-3 PUFAs in the blood. Further studies are required to gain additional insight into these associations in healthy subjects as well as into the causality of the relationship.

Mechanisms underlying the effects of n-3 polyunsaturated fatty acids on fear memory processing and their hypothetical effects on fear of cancer recurrence in cancer survivors.

The relationship of n-3 polyunsaturated fatty acids (PUFAs) and gut microbiota with brain function has been extensively reported. Here, we review how n-3 polyunsaturated fatty acids affect fear memory processing. n-3 PUFAs may improve dysfunctional fear memory processing via immunomodulation/anti-inflammation, increased BDNF, upregulated adult neurogenesis, modulated signal transduction, and microbiota-gut-brain axis normalization. We emphasize how n-3 PUFAs affect this axis and also focus on the hypothetical effects of PUFAs in fear of cancer recurrence (FCR), the primary psychological unmet need of cancer survivors. Its pathophysiology may be similar to that of post-traumatic stress disorder (PTSD), which involves dysfunctional fear memory processing. Due to fewer adverse effects than psychotropic drugs, nutritional interventions involving n-3 PUFAs should be acceptable for physically vulnerable cancer survivors. We are currently studying the relationship of FCR with n-3 PUFAs and gut microbiota in cancer survivors to provide them with a nutritional intervention that protects against FCR.

Serum pro-BDNF/BDNF as a treatment biomarker for response to docosahexaenoic acid in traumatized people vulnerable to developing psychological distress: a randomized controlled trial.

Our open-label pilot study showed that supplementation with docosahexaenoic acid (DHA) increased serum brain-derived neurotrophic factor (BDNF) levels and that there might be an association between changes in serum BDNF levels and reduced psychological distress. Animal research has indicated that a DHA-enriched diet increases BDNF in the brain. In this randomized double-blind controlled trial of severely injured patients vulnerable to posttraumatic stress disorder (PTSD) and depression, we examined whether DHA increases serum BDNF levels and whether changes in BDNF levels are associated with subsequent symptoms of PTSD and depression. Patients received 1470 mg per day of DHA plus 147 mg per day of eicosapentaenoic acid (EPA; n = 53) or placebo (n = 57) for 12 weeks. Serum levels of mature BDNF and precursor pro-BDNF at baseline and 12-week follow-up were measured using enzyme-linked immunosorbent assay kits. At 12 weeks, we used the Clinician-Administered PTSD Scale to assess PTSD symptoms and depressive symptoms by the Montgomery-Åsberg Depression Rating Scale. We found a significant increase in serum BDNF levels during the trial in the DHA and placebo groups with no interaction between time and group. Changes in BDNF levels were not associated with PTSD severity but negatively associated with depression severity (Spearman's ρ = -0.257, P = 0.012). Changes in pro-BDNF were also negatively associated with depression severity (Spearman's ρ = -0.253, P = 0.013). We found no specific effects of DHA on increased serum levels of BDNF and pro-BDNF; however, evidence in this study suggests that increased BDNF and pro-BDNF have a protective effect by minimizing depression severity.

CaNa2EDTA for improvement of radioimmunodetection and radioimmunotherapy with 111In and 90Y-DTPA-anti-CEA MAbs in nude mice bearing human colorectal cancer.

UNLABELLED: 111In and 90Y, dissociated from 111In-labeled-monoclonal antibody (MAb) and 90Y-labeled MAb, may cause deterioration of the image quality in radioimmunodetection (RID) and undesirable irradiation of nontargeted tissue in radioimmunotherapy (RIT), respectively. The aim of this study was to investigate any improvement in RID and RIT with 111In-MAb and 90Y-MAb by pre- and postadministration of calcium disodium ethylenetriaminetetraacetic acid (CaNa2EDTA). METHODS: Murine MAb F33-104 against carcinoembryonic antigen (CEA) was labeled with 111In or 90Y by the diethylenetriamine pentaacetic (DTPA)-anhydride method. The influence of CaNa2EDTA on loss of radioactivity from 111In-MAb or 90Y-MAb in serum was investigated in vitro. The effects of CaNa2EDTA, administered before and after 111In-MAb or 90Y-MAb, on the biodistribution of radioactive isotopes in nude mice bearing human colon adenocarcinoma LS 180 tumor expressing CEA, or human pulmonary carcinoma PC 9 tumor expressing no CEA, were then examined. As a control, 0.9% NaCl was used in both the in vitro and in vivo studies. RESULTS: CaNa2EDTA did not cause any decrease in levels of radioactivity of radiolabeled MAbs. Pre- and post-treatment with CaNa2EDTA reduced radioctivity in both specific and nonspecific tumors at 72 h after 111In-MAb injection resulting in an increase of the specific tumor-to-nonspecific tumor radioactivity ratio. The levels of hepatic and renal radioactivity were also subsequently decreased by CaNa2EDTA. On the other hand, CaNa2EDTA pre- and post-treatment reduced levels of bony, hepatic, and renal radioactivity at 24, 72, and 72 h, respectively, after 90Y-MAb injection, although it had no effect on tumor radioactivity. CONCLUSION: Pre- and post-treatment with CaNa2EDTA would be of great use in humans who undergo RID or RIT with 111In-MAb and 90Y-MAb accompanied by disassociation of the labeled radionuclides.

High water intake ameliorates tubulointerstitial injury in rats with subtotal nephrectomy: possible role of TGF-beta.

BACKGROUND: It has been shown that tubulointerstitial injury correlates well with a decline of renal function. In this study, we investigated the effect of high water intake (HWI) on functional and structural parameters in rats with subtotal nephrectomy. METHODS: Two weeks after the ablative procedure, rats were divided into two groups. One group received the treatment with HWI (3% sucrose added to drinking water) for eight weeks. Functional parameters were compared with sham-operated control (CONT) or nephrectomized rats without treatment (NX). Remnant kidneys were then assessed histologically for evidence of interstitial fibrosis and glomerulosclerosis. RESULTS: Creatinine clearance was significantly improved in HWI rats compared with NX rats. Simultaneously, urinary protein was also significantly reduced in HWI rats. HWI predominantly ameliorated interstitial lesions and, to a lesser extent, glomerular lesions. Northern blot analysis demonstrated that transforming growth factor-beta (TGF-beta) mRNA expression was significantly suppressed in HWI rats. In situ hybridization revealed that HWI suppressed TGF-beta mRNA expression mainly in the outer medulla. Fibronectin mRNA was also reduced by the HWI treatment. The changes in TGF-beta and fibronectin mRNA were in parallel with Na+/myo-inositol cotransporter (SMIT) mRNA, which is regulated by extracellular osmolarity. Immunohistochemistry demonstrated that protein expression of TGF-beta and fibronectin coincided with the mRNA expression. CONCLUSION: These results suggest that HWI reduces TGF-beta mRNA expression in medullary interstitium and ameliorates tubulointerstitial injury in rats with reduced renal mass.

Thymidylate synthase levels as a therapeutic and prognostic predictor in breast cancer.

5-Fluorouracil (5-FU) is a commonly used adjuvant therapeutic drug in treating breast cancer. 5-FU is metabolically converted to 5-fluorouracil-2'-deoxyuridine-5'-monophosphate-(FdUMP) which is believed to inhibit DNA synthesis in neoplastic cells by forming a tightly bound ternary complex with thymidylate synthase (TS). In the present study, we examined the possible relationship between TS levels and clinico-pathologic and prognostic features in breast disease. Mean TS levels of 2.9 pmol/g, 6.1 pmol/g, and 23.1 pmol/g were obtained in cases of benign breast disease (3 cases), primary breast cancer (115 cases), and recurrent tumors (4 cases), respectively. In breast cancer, mean TS levels significantly correlated with S-phase fraction (SPF), DNA polymerase a and lymphatic invasion. Thus, TS levels in breast cancer significantly reflected cell proliferation and malignancy. Regarding the survival rate, patients with TS values above 10 pmol/g showed an unfavorable prognosis. The effectiveness of adjuvant 5-FU derivatives chemotherapy was reflected in a higher disease-free survival rate in node (+) cases showing TS levels between 5 and 10 pmol/g (p < 0.1), but not in node (-) cases. In conclusion, TS levels in neoplastic tissues of the breast were highest in recurrent tumors, followed by those in primary cancer, benign breast disease and in breast cancer which reflected proliferative activity. Breast cancers with extremely high TS levels were accompanied by an unfavorable prognosis; however, those with moderately high TS levels tended to respond to adjuvant chemotherapy with 5-FU derivatives.

Complications associated with transcatheter arterial embolization for hepatic tumors.

Transcatheter arterial embolization (TAE) is widely used in the treatment of hepatic tumors. A total of 2,300 TAE procedures were performed with a 2-15-mL injection of a mixture or suspension of anticancer drugs and iodized oil, followed by administration of gelatin sponge particles. One or two chemotherapeutic drugs, including doxorubicin hydrochloride (10-30 mg), epirubicin hydrochloride (10-30 mg), mitomycin C (10-20 mg), and cisplatin (25-100 mg), were used for each procedure. Complications were encountered in 4.4% of cases (n = 102) and were related to the use of chemoembolic agents or the manipulation of a catheter or guide wire. These complications included acute hepatic failure (n = 6), liver infarction (n = 4) or abscess (n = 5), intrahepatic biloma (n = 20), multiple intrahepatic aneurysms (n = 6), cholecystitis (n = 7), splenic infarction (n = 2), gastrointestinal mucosal lesions (n = 5), pulmonary embolism or infarction (n = 4), tumor rupture (n = 1), variceal bleeding (n = 3), and iatrogenic dissection (n = 35) or perforation (n = 4) of the celiac artery and its branches. Knowledge of these complications is important for correct diagnosis and appropriate management.

Inhibition of myo-inositol transport causes acute renal failure with selective medullary injury in the rat.

Myo-inositol is a major compatible osmolyte in the renal medulla that is accumulated under hypertonic conditions via the Na+/myo-inositol cotransporter (SMIT). We have recently reported that SMIT is predominantly present in the thick ascending limb of Henle (TAL) and is strongly induced by acute NaCl loading, suggesting an important role of myo-inositol in this nephron segment. In the present study, we sought to examine in vivo effects of inhibition of myo-inositol transport using a transport inhibitor, 2-O, C-methylene-myo-inositol (MMI). Intraperitoneal injection of MMI caused acute renal failure in the rats. Serum creatinine and urea nitrogen were significantly increased 12 hours after MMI injection. Morphologic study revealed that the tubular cells were extensively injured in the outer medulla. A considerable number of the tubular cells were injured in the cortex as well. Immunohistochemical study for Tamm-Horsfall protein (THP), which was used for identification of the TAL cells, showed that THP-positive cells were predominantly injured. The tubular injury apparently appeared to worsen when high concentration of NaCl was injected with MMI. Administration of myo-inositol prevented acute renal failure and improved the tubular injury after MMI injection. Furthermore, supplementation of betaine, another osmolyte in the TAL cells, partially prevented the toxic effects of MMI. These results suggest that myo-inositol play a crucial role in the TAL regarding osmoregulation of the cells.

[Toxic shock-like syndrome after acupuncturation].

A 80-year-olkd male was admitted to our hospital because of severe pain and swelling on his left lower leg on January 23, 1996. He had received an acupuncture to both legs because of intermittent claudication once a week from July, 1995 to January 18, 1996. On the next day of the last acupuncture, pain and swelling on his left leg appeared. On admission, his left leg showed diffuse swelling and redness with blisters. We diagnosed this patient as toxic shock-like syndrome (TSLS), based on the rapid exacerbation of the skin changes, necrotizing superficial fasciitis, multiple organ failure with shock, and the detection of group A streptococcus from culture samples obtained from both skin blister and necrotic fascia. He recovered from the disease by amputation of the involved leg and antibiotic therapy. Acupuncture could have been the cause of streptococcal infection.

Plasmon analysis of Triticum (wheat) and Aegilops. 1. Production of alloplasmic common wheats and their fertilities.

Plasmons (= cytoplasms) of eight Triticum species (ten accessions) and 24 Aegilops species (36 accessions) have been introduced by repeated backcrosses to 12 genotypes of hexaploid, common wheat. At transfer problems such as crossing barrier, preferential transmission of a gametocidal or parthenogenesis-inducing chromosome, and mistagging of the material occurred, all of which hindered the plasmon transfer program. Of the 552 genotype-plasmon combinations produced, 532 (96.4%) had reached the B10 or a later backcross generation, 15 (2.7%) the B7 approximately B9 generation, and the remaining 5 (0.9%) the B4 approximately B6 generation by summer, 1996. Pollen and selfed seed fertilities were observed in plants of all the field-grown lines in the 1992-1993 winter crop season, and backcrossed and selfed seed fertilities of plants grown in a greenhouse under a long day condition (17-h light) were assessed in the five latest backcross generations. Selfed seed fertility was found to be a better parameter of male fertility than was pollen fertility. Female fertility, as estimated from the backcrossed seed fertility, was about three times more tolerant to genetic stress caused by the alien plasmon transfer than was male fertility evaluated from both the pollen and selfed seed fertilities. The plasmons studied could be classified into 14 fertility spectrum groups. Most, excluding 15 plasmons belonging to the B, D, D2, S, and Sb plasmon types, were considered the male sterile plasmon to common wheat.

Ameliorative effects of tea catechins on active oxygen-related nerve cell injuries.

Active oxygen species are suggested to be concerned with various senile disorders. Tea catechins, (+)catechin (CA), (-)epicatechin (EC) and (-)epigallocatechin gallate, are polyhydroxy-fravan derivatives from tea leaves and have been proposed to possess active oxygen scavenging effect. Tea catechins protected the cultured newborn-mouse cerebral nerve cells from death induced by glucose oxidase. The protective potency of (-)epigallocatechin gallate was weaker than those of EC and CA. Learning ability of mice was assessed by a step-down-type passive avoidance test, and memory impairment of mice was achieved by intracisternal injection of glucose oxidase or cerebral ischemia induced by 10 min occlusion of the common carotid arteries. Intracisternal injection of EC improved the memory impairment induced by intracisternal glucose oxidase, and i.v. injection of CA or EC improved that induced by the cerebral ischemia. CA and EC depressed carrageenin-induced edema in rat hind paw, but (-)epigallocatechin gallate did not. These results suggest that tea catechins ameliorate the injuries or impairments induced by active oxygens through scavenging intracellular active oxygens, and might become useful for protecting human from senile disorders such as dementia.

[Clinical studies on the treatment of Campylobacter enteritis--emergence of quinolone-resistant Campylobacter jejuni after treatment with new quinolones].

In recent years, new quinolones such as ofloxacin (OFLX) and tosufloxacin (TFLX) have been frequently used in the treatment of bacterial enteritis caused by unknown organisms. The agent of first choice for the treatment of Campylobacter enteritis is one of the macrolides, but new quinolones are often administered accidentally to adult patients with Campylobacter enteritis. We have detected quinolone-resistant strains of Campylobacter jejuni (C. jejuni) after the treatment of some patients with new quinolones, and accordingly we reviewed the treatment of Campylobacter enteritis. We experienced 178 adult patients with Campylobacter enteritis from January 1989 to November 1991 at our hospital. From them, we selected 52 patients (32 males and 20 females) in whom stool culture were performed both before and after treatment. The initially administered antimicrobial agent was a macrolide (rokitamycin, RKM) in 6 cases, a new quinolone in 22 cases, and kanamycin (KM) in 24 cases. The new quinolone used was OFLX in 17 cases, TFLX in 3 cases, and norfloxacin (NFLX) in 2 cases. Fifty-one of the 52 C. jejuni strains isolated before treatment were susceptible to OFLX and erythromycin (EM) according to antimicrobial disc susceptibility tests. C. jejuni was eradicated in all patients treated with RKM or KM. However, treatment failed to achieve bacteriological cure in 8/22 (36.4%) patients given new quinolones. In these patients, the strains of C. jejuni isolated before treatment were susceptible to OFLX, but the strains isolated after treatment were all resistant to OFLX according to disc susceptibility tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic ethanol injection of hepatocellular carcinomas undetectable by angiography and Lipiodol computed tomography.

Seven smaller than 2 cm in diameter hepatocellular carcinomas (HCC) undetectable by hepatic arteriography and computed tomography (CT) after intraarterial injection of iodized oil (Lipiodol CT) were diagnosed by ultrasonography-guided fine-needle biopsy in 6 patients. All lesions were treated by percutaneous ethanol injection (PEI) in 1-3 weekly intervals. No recurrences have been demonstrated after 7-15 months. The treatment of HCCs undetectable by angiography and Lipiodol CT presents a problem as transcatheter arterial embolization is considered ineffective due to poor vascularity. PEI appears to be an excellent treatment for these small HCCs.

Reduced somatostatin-like immunoreactivity in the brain of LEC rats with hepatic encephalopathy.

Somatostatin-14-like immunoreactivity (S14LI) and somatostatin-28(1-12)-like immunoreactivity (S28(1-12)LI) in the brain of LEC (Long Evans Cinnamon) rats with hepatic encephalopathy were measured. Significant reduction of both S14LI and S28(1-12)LI was observed in the hypothalamus, medulla oblongata, striatum and spinal cord. Both of the immunoreactivities in the hypothalamus of these rats were approx. 50% of those in LEC rats without hepatic encephalopathy. The amounts of reduction of S14LI significantly correlated with those of reduction of S28(1-12)LI. No significant difference in gel chromatographic profiles of S14LI and S28(1-12)LI was observed between LEC rats with and without hepatic encephalopathy. These results suggest that the reduction of somatostatin-like immunoreactivity in LEC rats with hepatic encephalopathy may be caused by a decrease in production of prosomatostatin rather than altered degradation.

[Diagnostic imaging of hepatic tumors].

There are several imaging methods for the detection of small hepatocellular carcinomas (HCC). The combined use of computed tomography (CT) and angiography is an excellent method. CT following intraarterial injection of iodized oil is a sensitive and useful examination for the detection of small hypervascular HCCs. CT during arterial portography is superior in visualizing small hypovascular HCCs. These methods are complementary to each other. Magnetic resonance imaging (MRI) is a new examination. T1 and T2 of the HCC are usually longer than normal hepatic parenchyma. HCCs greater than 2 cm are almost detected by MRI.

Characteristic of analgesia induced by noncatecholic phenylethylamines in mice.

Using hot plate method, analgesia induced by noncatecholic phenylethylamines, phenethylamine, phenylethanolamine and amphetamine, was inhibited by naloxone, reserpine, apomorphine and p-chlorophenylalanine, while potentiated by haloperidol. These results suggest that phenylethylamines induced analgesia involves central dopaminergic and serotonergic neurons and endogenous opioid peptides. The blockade of dopaminergic neurons enhanced and the inhibition of serotonergic neuron activity or the stimulation of dopaminergic neurons attenuated the phenylethylamines induced analgesia. Using rat hind paw pressing or tail flick test, analgesia induced by electroacupuncture in which Hoku points were electrically stimulated through stainless steel needles was enhanced by phenylethylamines, haloperidol while attenuated by naloxone, reserpine, apomorphine and p-chlorophenylalanine. Thus the analgegic characteristic of phenylethylamines closely resembles that of electroacupuncture.