Effects of Roasting Conditions on Antibacterial Properties of Vietnamese Turmeric (Curcuma longa) Rhizomes.

Processing with heat treatment has been reported to alter several therapeutic effects of turmeric. In Vietnamese traditional medicine, turmeric has been long used for bacterial infections, and roasting techniques are sometimes applied with this material. However, there have been no studies investigating the effects of these thermal processes on the plant's antibacterial properties. Our study was therefore performed to examine the changes that roasting produced on this material. Slices of dried turmeric were further subjected to light-roasting (80 °C in 20 min) or dark-roasting (160 °C in 20 min) processes. Broth dilution and agar-well diffusion methods were applied to examine and compare the effects of ethanol extracts obtained from non-roasted, light-roasted and dark-roasted samples, on a set of 6 gram-positive and gram-negative bacteria. In both investigations, dark-roasted turmeric was significantly less antibacterial than non-roasted and light-roasted materials, as evident by the higher values of minimum inhibitory concentrations and the smaller diameters of induced inhibitory zones. In addition, dark-roasting was also found to clearly reduce curcumin contents, total polyphenol values and antioxidant activities of the extracts. These results suggest that non-roasting or light-roasting might be more suitable for the processing of turmeric materials that are aimed to be applied for bacterial infections.

Short communication: Antibacterial effects of essential oils from Cinnamomum cassia bark and Eucalyptus globulus leaves-The involvements of major constituents.

Essential oils from Cinnamomum cassia bark and Eucalyptus globulus leaves have been traditionally applied for bacterial infections, through both of aromatherapy and oral application. (E)-cinnamaldehyde and 1,8 cineole have been identified as their major secondary metabolites, and are also generally considered as the main active ingredients responsible for their medicinal applications. However, ethnobotanical doctors still prefer to use whole essentials oils over purified compounds in bacterial infections. We therefore hypothesized that multi-compound extracts might exert better effects than isolated ingredients. In order to verify the hypothesis about advantages of whole materials, we examined antibacterial properties of the 2 plant essential oils in the comparison with their isolated major compounds, such as (E)-cinnamaldehyde and 1,8 cineole. Effects of liquid- and vapor-phase were examined on a set of 6 gram-positive and -negative bacteria, applying broth dilution, agar well diffusion and disc volatilization methods. In all 3 investigations, we observed that whole cinnamon and eucalyptus oils, with the lower concentrations of (E)-cinnamaldehyde (89.1%) and 1,8 cineole (61.2%), were able to induce better effects than the purified active compounds (≥ 99%). These results partly explain the advantages of using whole essential oils over isolated ingredients, and therefore support the application of traditional dosage forms for bacterial infections in ethnomedicine.

Circulating Tumor DNA as a Potential Prognostic Marker in Patients with Borderline-Resectable Pancreatic Cancer Undergoing Neoadjuvant Chemotherapy Followed by Pancreatectomy.

BACKGROUND: Circulating tumor DNA (ctDNA) might be a promising biomarker for pancreatic cancer in liquid biopsy. This study aimed to evaluate the usefulness of liquid biopsy for patients with borderline-resectable pancreatic cancer (BR-PC). METHODS: Patients with BR-PC according to the National Comprehensive Cancer Network guidelines (2017) and eligible for neoadjuvant chemotherapy (NAC) followed by pancreatectomy were recruited at Wakayama Medical University Hospital (UMIN000026647) between March 2017 and April 2020. The study enrolled 55 patients with locally advanced PC, and each patient consented to inclusion in the study. The study investigated the relationship between KRAS status in ctDNA and clinicopathologic features, analyzing ctDNA at three time points: pretreatment, post-NAC, and post-operation. RESULTS: Of the 55 enrolled patients with a diagnosis of BR-PC, 34 were scheduled to undergo pancreatectomy. From 27 patients with resected BR-PC, 81 blood samples were analyzed in triplicate for ctDNA. The patients with positive pretreatment and post-NAC ctDNA status had no significant decrease in median relapse-free survival (RFS) or overall survival (OS). However, the patients with positive postoperation ctDNA status had a significantly shorter median OS (723 days) than the patients with negative ctDNA results (not reached; P = 0.0148). A combined analysis of postoperative ctDNA and CA19-9 values showed the cumulative effect on both RFS (P = 0.0066) and OS (P = 0.0046). The adjusted hazard ratio for risk of survival computed for the patients carrying risk factors (either detectable ctDNA or CA19-9 > 37 U/ml) increased from 4.13-fold to 17.71-fold (both P = 0.0055) compared with the patients who had no risk factors. CONCLUSION: Positive ctDNA predicts poor survival for patients with BR-PC who undergo NAC followed by pancreatectomy.

Ninjin'yoeito Ameliorates Skeletal Muscle Complications in COPD Model Mice by Upregulating Peroxisome Proliferator-Activated Receptor γ Coactivator-1α Expression.

Purpose: Sarcopenia, the loss of skeletal muscle mass and strength, is a common systemic consequence of chronic obstructive pulmonary disease (COPD) and is correlated with higher mortality. Ninjin'yoeito (NYT) is a Japanese herbal medicine used to treat athrepsia and anorexia and is reported to ameliorate weight loss and muscular dysfunction. Recent studies have shown that its crude components upregulate the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-related pathway, which is involved in skeletal muscle functions. Here, we examined whether NYT improves skeletal muscle complications by upregulating PGC-1α in COPD model mice. Materials and Methods: Mice were divided into four groups: control, NYT, smoking, and smoking + NYT. The smoking and smoking + NYT groups were exposed to cigarette smoke for 60 min once daily. The mice in the NYT and smoking + NYT groups were fed an NYT-containing diet (3% w/w). We performed cellular analysis of bronchoalveolar lavage fluid, assessed pulmonary morphological changes, examined the expression of PGC-1α mRNA and protein in the gastrocnemius and soleus muscle, measured the hindlimb muscle volume with micro-computed tomography, and determined the myofiber proportion in soleus muscle after 12 weeks. Results: Cigarette smoke exposure resulted in reduced skeletal muscle volume and slow-twitch muscle fibers and development of pulmonary emphysema. NYT feeding induced partial recovery of the damaged alveolar wall; however, NYT did not ameliorate smoke-induced alveolar enlargement. These findings revealed that NYT did not have sufficient efficacy in suppressing pulmonary emphysema. On the other hand, PGC-1α expression in muscle tissue of the NYT-fed mice increased significantly, resulting in suppression of smoke-induced loss of muscle mass and alteration in the muscle fiber distribution. Conclusion: NYT increases PGC-1α expression in the muscle of COPD model mice and is involved in suppressing cigarette smoke-induced muscle complications. NYT may be a novel preventive and therapeutic medication for muscular dysfunctions in COPD.

[A Case of Advanced Gastric Cancer with Umbilical Metastasis, Pyloric Stenosis, and Peritoneal Dissemination Underwent Palliative Surgery after Chemotherapy].

A 62-year-old woman was diagnosed with gastric cancer, Type 4, cT4b(LN, mesentery of transverse colon), N1 M1H0P1CY1, cStage ⅣB. S-1 and L-OHP(SOX)were administered for 4 courses and clinical response was SD. She interrupted the treatment because of practicing folk therapy. She had an emergency hospitalization due to pyloric stenosis, vomiting, and an umbilical tumor with pain. She was treated with 1 course of mFOLFOX6(5-FU, L-OHP, l-LV)followed by palliative surgery(laparoscopy assisted distal gastrectomy, Roux-en-Y reconstruction, resection of umbilical tumor, and bypass for transverse colon stenosis due to dissemination). The pathological diagnosis was L, Circ, Type 4, 126×89 mm, por> sig, pT4b(SI, mesentery of transverse colon), pN3a(12/13), H0P1CY1, pStageⅣ, and metastatic umbilical tumor. Following surgery, oral administration of mFOLFOX6 is continued. Umbilical metastasis(Sister Mary Joseph's nodule)is associated with poor prognosis, however, appropriate management including symptom control by palliative surgery and continuation of chemotherapy may lead a better prognosis.

Endothelium-independent and calcium channel-dependent relaxation of the porcine cerebral artery by different species and strains of turmeric.

OBJECTIVE: To clarify the underlying mechanism of turmeric, which is traditionally used as a medicinal plant for the treatment of cardiovascular disorders, such as hypertension, and palpitations. METHODS: Methanol extracts of different turmeric were used. A tissue-organ-bath system was used to investigate the vasoactive effects of methanol extracts from 5 kinds of turmeric on isolated porcine basilar arteries. The arterial rings were suspended in physiological solution that was maintained at 37 °C temperature with a continuous supply of 95% O2 and 5% CO2. RESULTS: All turmeric extracts (20-800 µg/mL) induced concentration-dependent relaxation of the isolated porcine basilar artery pre-contracted with U46619 (1-5 × 10-9 M) in arterial rings with or without endothelium. There were no significant differences in the relaxation induced by different turmeric or between the endothelium-intact and denuded arteries. In depolarized, Ca2+-free medium, the turmeric extracts inhibited CaCl2-induced contractions and caused a concentration-dependent rightward shift of the response curves. In addition, propranolol (a non-specific ß-adrenoceptor antagonist) slightly inhibited the relaxation induced by turmeric. In contrast, Nω-nitro-l-arginine, indomethacin, tetraethylammonium, glibenclamide and 4-aminopyridine did not affect turmeric-induced relaxation. CONCLUSION: These results demonstrated that turmeric induced endothelium-independent relaxation of the porcine basilar artery, which may be due to the inhibition of extracellular and intracellular Ca2+ receptors and the partial inhibition of ß-adrenergic receptors in vascular smooth muscle cells.

Antagonistic Effects of Gingko biloba and Sophora japonica on Cerebral Vasoconstriction in Response to Histamine, 5-Hydroxytryptamine, U46619 and Bradykinin.

The aim of this study was to evaluate, for the first time, the antagonistic effects of Gingko biloba leaf (GB) and Sophora japonica L. flower bud (SJ) extracts on cerebral vasoconstriction in response to KCl, extracellular Ca[Formula: see text], histamine, 5-hydroxytryptamine (5-HT), 9,11-dideoxy-9[Formula: see text],11[Formula: see text]-methanoepoxy prostaglandin (PG) F[Formula: see text](U46619) and bradykinin (BK), in order to explain their traditional application for diseases associated with cerebral vasospasm. Isolated porcine basilar arteries (PBA) and endothelial cells from them were used as the study materials. Neither SJ nor GB had any effect on the contractions induced by KCl and extracellular Ca[Formula: see text]. SJ significantly inhibited the contraction induced by histamine, 5-HT, U46619 and BK, whereas GB inhibited histamine-induced contraction, but had no effects on the contractions induced by 5-HT, U46619 and BK. In the presence of diphenhydramine (a H1 receptor antagonist), ketanserin (a 5-HT2 receptor antagonist) and ONO-3708 (a thromboxane (TX) A2/PG receptor antagonist), the inhibitory effects of these extracts on the contractions induced by histamine, 5-HT and U46619 were abolished. SJ significantly inhibited the contractions induced by BK and PGF[Formula: see text], but in the presence of ONO-3708 (10[Formula: see text] M) had no effect on them. BK enhanced the production of PGF[Formula: see text] from cultured PBA endothelium cells, and SJ significantly attenuated this enhancement. These results suggest that SJ and GB have a H1-antagonistic effect, and that SJ also attenuates cerebral vasoconstriction mediated via 5-HT2 and TXA2/PG receptors. These findings appear to explain why SJ has been used traditionally as a therapeutic medication for cerebral vasospasm after cerebral hemorrhage.

Pharmacological characteristics of Artemisia vulgaris L. in isolated porcine basilar artery.

ETHNOPHARMACOLOGICAL RELEVANCE: In Vietnamese traditional herbalism, there are conflicting opinions about the effect of Artemisia vulgaris L. (AVL, English name: mugwort) on hypertension. Some ethnic doctors recommend the use of AVL for treatment of hypertension, whereas others advise against it. The purpose of this study was to clarify the pharmacological characteristics of AVL in isolated arteries to explain the conflicts surrounding the use of AVL for treatment of hypertension. MATERIALS AND METHODS: We initially performed a functional study using an organ bath system to investigate the effect of AVL extract on isolated porcine basilar artery. We then measured the change in intracellular free Ca(2+) concentration elicited by AVL using cultured smooth muscle cells loaded with the Ca(2+) indicator fluo-4. Finally, using HPLC, we determined the active components in AVL. RESULTS AND DISCUSSION: AVL induced vasoconstriction at resting tension, and endothelial removal enhanced this effect significantly. Pretreatment with PD123319 (an AT2 receptor antagonist), Nω-nitro-L-arginine (a nitric oxide synthase inhibitor), or both, also enhanced this effect. AVL-induced contraction was competitively inhibited by methiothepin (a 5-HT1 and 5-HT2 receptor antagonist) in the presence of ketanserin (a 5-HT2 receptor antagonist). Removal of extracellular calcium with nifedipine (an L-type Ca(2+) channel blocker) or ruthenium red (a ryanodine receptor blocker) significantly reduced AVL-induced contraction, whereas losartan (an AT1 receptor antagonist) and diphenhydramine (a H1 receptor antagonist) had no effect on this contraction. AVL increased the intracellular free Ca(2+) concentration in cultured cells, and this increment was inhibited by methiothepin. HPLC analysis revealed that the retention time of the first peak in the AVL profile was similar to that of the 5-HT standard, and that addition of 5-HT to the AVL sample enhanced this peak. On the other hand, AVL induced endothelium-independent relaxation under precontracted conditions with 60mM KCl. Captopril (an angiotensin converting enzyme inhibitor), atenolol (a ß1 receptor antagonist) and cimetidine (a H2 receptor antagonist) had no effect on this relaxation. In Ca(2+)-free 60mM KCl-containing solution, pretreatment with AVL significantly inhibited CaCl2-induced contraction. CONCLUSION: For the first time, the present study has demonstrated that AVL has two opposite effects, contraction and relaxation, on isolated artery, which may help to explain the conflicting indications for AVL in traditional herbalism. 5-HT is a significant factor affecting artery contraction in the presence of AVL.

[A case of HER2-positive advanced gastric cancer with extensive lymph node metastasis treated via chemotherapy with a trastuzumab-containing regimen followed by conversion surgery].

A 62-year-old man presented with type 3 gastric cancer (tub1, HER2 positive) in the cardia, with 10-cm direct invasion into the lower esophagus, and extensive lymph node metastasis (Virchow and paraaortic nodes). Trastuzumab (Her), in the XP regimen (capecitabine and cisplatin [CDDP] plus Her; Xeloda®: 2,000 mg/m² on day 1-14, CDDP: 80 mg/m² on day 1, Her: 8(6) mg/kg on day 1), was administered every 3 weeks and repeated for 6 courses. After administering 6 courses of the XP plus Her regimen, without severe adverse events in the patient, computed tomography (CT) revealed shrinkage of both the main tumor and the metastatic sites, by 51%. Esophagectomy and proximal gastrectomy with 3-field lymphadenectomy and gastric tube reconstruction was performed via right thoracotomy and laparotomy (R0). However, Grade 3 pneumonia occurred postoperatively, and the patient was discharged on day 67 after surgery. After treatment, the tumor was histologically evaluated as Grade 1b gastric cancer, and remnant cancer cells also expressed HER2. The patient was too frail to receive adjuvant chemotherapy, and he died of pneumonia 11 months after surgery, without obvious relapse. Perioperative chemotherapy with a regimen containing Her has a possible role in treating advanced HER2-positive gastric cancer. Multiple invasive conversion surgeries might decrease the feasibility of adjuvant chemotherapy and worsen the prognosis.

Nitric oxide-dependent hypotensive effects of wax gourd juice.

ETHNOPHARMACOLOGICAL RELEVANCE: The wax gourd (Benincasa hispida (Thunb) Cong.) is a long-season vegetable that has been used in traditional Chinese medicine to treat high blood pressure. However, precise details of its effect and the mechanism of action involved are still lacking. MATERIALS AND METHODS: Ten-fold-condensed wax gourd juice was used for the experiments. We measured (1) blood pressure of anesthetized normal Wistar rats in vivo, (2) isolated rat aortic contraction and relaxation, and (3) nitric oxide production from cultured porcine endothelial cells. The rats mentioned had not been treated with the investigational medicine. RESULTS: Intravenous injection of the juice produced a dose-dependent decrease in blood pressure. Treatment with the juice induced concentration-dependent relaxation of isolated rat aortic rings that had been precontracted with noradrenaline. The relaxation induced by the juice was strongly inhibited by treatment with the nitric oxide (NO) synthase inhibitor N(G)-nitro-l-arginine methyl ester hydrochloride (l-NAME) or endothelial denudation. Treatment with the juice produced NO from cultured porcine aortic endothelial cells. This NO production was significantly inhibited by l-NAME. CONCLUSIONS: The present findings suggest that wax gourd juice exerts a hypotensive effect via endothelium-dependent vasodilation. The main endothelium-derived relaxing factor involved might be NO.

Vestibular evoked myogenic potentials of undiagnosed dizziness.

OBJECTIVE: Recording of vestibular evoked myogenic potentials (VEMP) can facilitate the evaluation of otolith function. The dizziness caused by otolith lesions is not completely understood. To clarify which symptoms of dizziness originate from the otolith organs, we examined the relationship between symptoms and VEMP results in patients with undiagnosed dizziness. METHODS: The subjects were 18 patients with undiagnosed dizziness aged less than 40 years who underwent VEMP examination. The VEMP results were evaluated using the interaural ratio of p13-n23 amplitude. RESULTS: Abnormal VEMP results were obtained in five of seven patients who experienced a sensation of falling (p=0.013), in none of the three patients who experienced a swaying sensation (p>0.05), and in one of eight patients who experienced a floating sensation (p>0.05). Five of six patients with abnormal VEMP results complained of disequilibrium lasting a few seconds. CONCLUSIONS: Dizziness with a sensation of falling lasting for a few seconds was related to abnormal VEMP results, suggesting that it resulted from saccular dysfunction. VEMP examination may be considered a useful modality in the diagnosis of dizziness of unknown origin.

Hepatic resection followed by IFN-alpha and 5-FU for advanced hepatocellular carcinoma with tumor thrombus in the major portal branch.

BACKGROUND/AIMS: The prognosis of hepatocellular carcinoma (HCC) invading the major branches of the portal vein (Vp3) is extremely poor. Recently, we reported the efficacy of combination therapy with subcutaneous interferon (IFN)-alpha and intra-arterial 5-FU for intractable HCC with Vp3. In this study, this therapy was applied for resectable advanced HCC (Vp3) as a postoperative adjuvant. METHODOLOGY: Patients with HCC and tumor thrombi either in the major or first branch of portal vein were included (n=30). Fifteen consecutive patients with HCC and Vp3 were treated with at least 3 cycles of a combination therapy consisting of continuous arterial infusion of 5-FU (300 mg/mm3/day, 5 days/week, for the initial 2 weeks) and subcutaneous injection of IFN (5 MIU, 3 times/week, 4 weeks) as a postoperative adjuvant therapy following hepatic resection. Another 15 patients who underwent hepatic resection with no IFN/5-FU chemotherapy acted as controls. RESULTS: The results were as follows in the IFN/5-FU adjuvant treatment group; disease-free survival (n=11, 5-55 months), survival with recurrence (n=2, 9, 48 months), cancer death (n=1, 18 months), death from other causes but no recurrence (n=l, 22 months). The 1-year survival rate was 100% in patients treated with IFN/5-FU, and 41% in those without IFN/5-FU historical controls (n=15). There was a significant difference in disease-free and overall survival rates between the two groups (p = 0.0033 and 0.0031). CONCLUSIONS: Combination therapy with subcutaneous IFN and intra-arterial perfusion of 5-FU seems to be a promising postoperative adjuvant treatment modality for resectable HCC with Vp3.

Frequency dynamics shift of vestibular evoked myogenic potentials in patients with endolymphatic hydrops.

OBJECTIVE: To measure the frequency dynamics of the vestibular evoked myogenic potential in patients with endolymphatic hydrops. STUDY DESIGN: A prospective study. SETTING: A university hospital. SUBJECTS: The endolymphatic hydrops group consisted of 28 affected ears of patients with definite unilateral Ménière's disease and a control group of 36 ears of 20 healthy volunteers. INTERVENTIONS: Vestibular evoked myogenic potentials generated by tone bursts at 250, 500, 700, 1,000, 1,500, 2,000, and 4,000 Hz were measured in both groups. Vestibular evoked myogenic potentials were also measured after furosemide administration in six patients in the endolymphatic hydrops group. MAIN OUTCOME MEASURE: The frequency sensitivity of vestibular evoked myogenic potential, as evaluated by p13-n23 normalized amplitude. RESULTS: Peak amplitudes were noted at 500 Hz in the control group and at 1,000 Hz in the endolymphatic hydrops group. After furosemide loading, peak amplitude shifted to a lower frequency in four of six ears. CONCLUSION: The peak amplitude of vestibular evoked myogenic potentials in the endolymphatic hydrops group was at a higher frequency than in the control group. The frequency of the saccule (nu) should be proportional to radical(tau/sigma), where tau is the tension of membrane and sigma is its density. We advocate the hypothesis that the shift in frequency dynamics of vestibular evoked myogenic potential in patients with endolymphatic hydrops originates from the morphologic features of the saccule, analogous to an expanded balloon.

[A case of long-term survival with TAE resistant multiple recurrence HCC successfully treated by hepatic resection].

A 55-year-old female was admitted to our hospital for a third recurrence of hepatoma. She was treated with transcatheter arterial embolization (TAE) in April and November 1996. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed multiple tumors of S4/S8 and S7 in the liver. After the third TAE using SMANCS, Lipiodol and Spongel, abdominal CT revealed insufficient Lipiodol retention and the in efficacy of this treatment. A right lobectomy of the liver was performed for the TAE resistant multiple recurrence of HCC. After the surgery, the patient survived for over 5 years with no recurrence. It appears that this surgery may be a useful modality for TAE resistant multiple recurrence hepatoma in cases of good liver function and lesions limited to the hemi lobe.

Mechanisms underlying the enhanced elevation of IL-1beta and TNF-alpha mRNA levels following endotoxin challenge in rat alveolar macrophages cultured with low-Mg2+ medium.

We have previously shown that interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha mRNA levels in rat alveolar macrophages are increased in by endotoxin (lipopolysaccharide; LPS)- stimulation and further enhanced by culturing with low-Mg2+ medium. We have now investigated the mechanisms of underlying this enhancement by using some specific signal transduction inhibitors. The enhanced elevation of both mRNAs levels was suppressed by pretreatment with TMB-8 (which inhibits calcium release from the endoplasmic reticulum) or dexamethasone (which inhibits nuclear factor [NF]-kappaB and activator protein [AP]-1), but not with verapamil or nifedipine (which inhibits calcium channels). The enhancment of IL-1beta, but not TNF-alpha mRNA levels, was suppressed by pretreatment with W-7 (which inhibits calmodulin), whereas the enhancement of TNF-alpha mRNA levels was suppressed by pretreatment with U73122 (which inhibits phospholipase C). Curcumin (an inhibitor of AP-1), suppressed the increases in both mRNAs induced by low-Mg2+ medium alone, but had no suppressive effect on the levels of either mRNA after LPS-stimulation in low-Mg2+ medium. Pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB) prevented the elevation of TNF-alpha mRNA levels induced by low-Mg2+ medium without LPS-stimulation, but had no suppressive effect on IL-1beta mRNA levels. From these results, we conclude that the enhanced elevation of IL-1beta and TNF-alpha mRNA levels seen in LPS-stimulated alveolar macrophages in low-Mg2+ medium occurs partly via the same, and partly via different, signaling pathways.