Tea crude extracts effectively inactivate severe acute respiratory syndrome coronavirus 2.

It is well known that black and green tea extracts, particularly polyphenols, have antimicrobial activity against various pathogenic microbes including viruses. However, there is limited data on the antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged rapidly in China in late 2019 and which has been responsible for coronavirus disease 2019 (COVID-19) pandemic globally. In this study, 20 compounds and three extracts were obtained from black and green tea and found that three tea extracts showed significant antiviral activity against SARS-CoV-2, whereby the viral titre decreased about 5 logs TCID50 per ml by 1·375 mg ml-1 black tea extract and two-fold diluted tea bag infusion obtained from black tea when incubated at 25°C for 10 s. However, when concentrations of black and green tea extracts were equally adjusted to 344 µg ml-1 , green tea extracts showed more antiviral activity against SARS-CoV-2. This simple and highly respected beverage may be a cheap and widely acceptable means to reduce SARS-CoV-2 viral burden in the mouth and upper gastrointestinal and respiratory tracts in developed as well as developing countries.

Induction of cytochrome P450 1B1 in lung, liver and kidney of rats exposed to diesel exhaust.

We have shown previously that diesel exhaust particle (DEP) extracts (DEPE) and 1-nitropyrene were genotoxically activated by human cytochrome P450 1B1 in SOS/umu assay. In this study, the in vivo induction of P450 family 1 enzymes in rats by exposure to diesel exhaust was investigated with regard to mRNA levels, P450 enzyme content, drug oxidation activities in the microsomes and umu gene expression of typical P450 substrates and DEPE itself catalyzed by the microsomes. Male Fischer 344 rats (4 weeks old) were exposed to 0.3 and 3.0 mg/m(3) DEP for 12 h per day for 4 weeks; the former dose corresponded to the typical daily airborne particle concentration. The levels of mRNA of rat P450 1B1 and P450 1A1 in the lung and liver were significantly increased 1.1-1.4-fold by exposure to 0.3 mg/m(3) DEP. Diesel exhaust particle extracts induced umu gene expression in Salmonella typhimurium TA1535/pSK1002 in the absence of a functional P450 system and were further activated by human recombinant P450 1B1. Using an O-acetyltransferase overexpressing Salmonella strain, genotoxic activation of P450 1B1 marker chemicals (1-nitropyrene, 1-aminopyrene and DEPE) by lung, liver and kidney microsomes was increased 1.7-4.2-, 1.4-1.5- and 1.0-1.3-fold, respectively, by exposure to 0.3 mg/m(3) DEP. Activation of 3-amino-1,4-dimethyl-5H-pyrido [4,3-b]indole (Trp-P-1; marker for P450 1A1) by lung microsomes and the P450 1A2 content in liver microsomes were slightly increased by exposure to 3.0 mg/m(3) DEP. This is the first report to suggest that typical daily contaminant levels (0.3 mg particle/m(3)) of diesel exhaust can induce P450 1B1 in rats and that the induced P450 1B1 may catalyze the genotoxic activation of DEP.

Metabolic activation of carcinogenic 1-nitropyrene by human cytochrome P450 1B1 in Salmonella typhimurium strain expressing an O-acetyltransferase in SOS/umu assay.

Metabolic activation of 1-nitropyrene (1-NP) by human cytochrome P450 (P450) family 1 enzymes co-expressed with NADPH-cytochrome P450 reductase (NPR) in Escherichia coli membranes was investigated. 1-NP induced umu gene expression in Salmonella typhimurium TA1535/pSK1002 in the absence of any P450 system, but the activities were influenced by the levels of bacterial O-acetyltransferase (OAT) and nitroreductase. Metabolic activation of 1-NP by human P450 1B1/NPR membranes was observed and was influenced by the levels of OAT levels in tester strains. Metabolic activation of 1-NP (0.3microM) by P450 1B1 was 750 umu units/min/nmol P450 1B1 in an OAT-overexpressing strain NM2009. The metabolic activation of 1-NP (3-30microM) was similar (approximately 300 umu units/min/nmol P450 1B1) using TA1535/pSK1002 or OAT-deficient strain NM2000. P450 1B1 had the highest catalytic activities among P450 family 1 enzymes for the activation of 1-aminopyrene (1-AP) in the OAT-overexpressing strain NM2009, suggesting nitrenium ion formation via N-hydroxylation/O-acetylation. High-performance liquid chromatography (HPLC) analyses revealed the formation of 1-nitropyrene-6-ol and also 1-nitropyrene-3-ol, 1-nitropyrene-8-ol, and trans-4,5-dihydroxy-4,5-diol-1-nitropyrene from 1-NP (10microM), catalyzed by P450 1B1. These results indicate that 1-NP can be activated by human P450 1B1 to a genotoxic agent by nitroreduction/O-acetylation at low substrate concentrations and probably by epoxidation (independent of OAT) at high concentrations.

Bioactivation of diesel exhaust particle extracts and their major nitrated polycyclic aromatic hydrocarbon components, 1-nitropyrene and dinitropyrenes, by human cytochromes P450 1A1, 1A2, and 1B1.

The genotoxicities of four samples of diesel exhaust particle (DEP) extracts (DEPE) and nine nitroarenes found in DEPE were investigated after activation catalyzed by human cytochrome P450 (P450) family 1 enzymes co-expressed with NADPH-cytochrome P450 reductase (NPR) in Escherichia coli membranes. The DEPE samples induced umu gene expression in Salmonella typhimurium TA1535/pSK1002 without any P450 system and were further activated by human P450 1B1/NPR membranes. Moderate activation of the DEPE sample by P450 1A2/NPR membranes was also observed, but not by either P450 1A1/NPR or NPR membranes. 1-Nitropyrene (1-NP) was strongly activated by human P450 1B1/NPR membranes. 1,8-Dinitropyrene (1,8-DNP) was most highly activated by P450 1A1 and 1B1 systems for the three DNPs tested. In contrast, 1, 3-DNP was inactivated by P450 1A1/NPR, 1A2/NPR, and 1B1/NPR systems and slightly activated by NPR membranes. 2-Nitrofluoranthene (2-NF) and 3-nitrofluoranthene (3-NF) showed activities similar to 1-NP after bioactivation by P450 1B1/NPR membranes. However, the genotoxicities of 6-nitrochrysene, 7-nitrobenz[a]anthracene, and 6-nitrobenzo[a]pyrene were all weak in the present assay system. Apparent genotoxic activities of DEPE were very low compared with standard nitroarenes in the presence of P450s, possibly because unknown component(s) of DEPE had inhibitory effects on the bioactivation of 1-NP and 1,8-DNP catalyzed by human P450 1B1. These results suggest that environmental chemicals existing in airborne DEP, in addition to 1-NP, 1,6-DNP, 1,8-DNP, 2-NF, and 3-NF, can be activated by human P450 1B1. Biological actions of air pollutants such as nitroarenes to human extrahepatic tissues may be of concern in tissues in which P450 1B1 is expressed.

Selenium kinetics and changes in glutathione peroxidase activities in patients receiving long-term parenteral nutrition and effects of supplementation with selenite.

Selenium (Se) is an essential trace element in humans. Patients receiving long-term parenteral nutrition (PN) are at risk for Se deficiency. We investigated changes in Se levels and glutathione peroxidase (GSH-Px) activity in serum and tissue (red blood cells, RBC) in addition to urinary excretion of Se in patients receiving long-term PN with and without Se supplementation. In patients without Se supplementation, both Se levels and GSH-Px activity in serum decreased with duration of PN. The serum Se levels were below the lower limits of the control values in 19 of 33 patients (58%) who received PN for less than 1 mo. Conversely, RBC GSH-Px activity remained at a sufficient level in 9 of 12 patients (75%) who received PN for 3-6 mo. The RBC Se levels in all of these patients were lower than the control levels. Urinary Se concentrations were significantly correlated with serum Se concentrations by linear regression analysis (r = 0.707, P < 0.05). In patients with Se supplementation, urinary Se concentrations increased exponentially with increases in serum Se levels. These findings indicate that a time lag precedes the decrease in levels of serum Se, RBC Se, serum GSH-Px, and RBC GSH-Px in patients without Se supplementation and the increase in excretion of urinary Se in patients with Se supplementation. The monitoring of not only serum Se levels but also RBC GSH-Px activity and urinary Se levels is required for optimal Se supplementation during long-term PN.

[A patient with dysphagia treated successfully and discharged without nutritional support].

One of the main targets of medical care provided in our ward, which specializes in the cooperative practice of hospital- and home-doctors, is to maintain the quality of patients' lives after they are discharged from our hospital through home medical care by home-doctors. Intravenous hyperalimentation and tube-feeding at home are suitable solutions for some patients with dysphagia after cerebral infarction. However, the difficulties faced in their management are the burden on the families, which tends to be an obstacle for at-home-practice. We describe herein a case of severe dysphagia treated successfully through our rehabilitation program and discharged without nutritional supports. An 82-year-old man was admitted to our hospital suffering from pyrexia and dysbasia. The man, who lives with his wife and his son's family, was diagnosed with aspiration pneumonia and multiple cerebral infarctions. The test for swallowing reflex revealed an impaired first phase reflex and intravenous hyperalimentation was performed for his nutritional support. He was still suffering from dysphagia but had the desire to eat orally after his dysbasia and aspiration pneumonia were cured. A rehabilitation program was scheduled with the aims of 1) recovery of ingestion and 2) sufficient expectoration, with an ongoing teaching program for the management of intravenous hyperalimentation. After one month of rehabilitation (ice-massaging, muscle rehabilitation of the tongue and neck and expectoration training in a prone position and after gorging), his ability to swallow was gradually recovered. With the frequent confirmation of absence of aspiration, special forms of diets were served and upgraded from jelly, paste-like-food to soft-cooked steamed rice. The patient is now at home without any nutritional support. Nutritional management without intravenous hyperalimentation or tube-feeding is important or even essential for some families providing home-care for patients. The problem of aging requires us to reduce the burden that families (who may be also getting older) should carry. We try to support patients and families for better home-care through cooperation with society and home-doctors.

[A successfully treated case of empyema with a large tracheal fistula after subtotal esophagotomy by mediastinoscopy].

We reported a successfully treated case of empyema with a large tracheal fistula after subtotal esophagotomy. This 59-year-old male was treated by drainage with mediastinoscopy and repeated wash-out under bronchoscopy, because we could not use the omentum and he was the poor-risk patient. The trancheal fistula was obliterated bronchoscopically, 4 months after the mediastinoscopy. We believe that this method (abscess drainage with mediastinoscope and wash-out repeatedly) is useful for those who has broncheal fistula after esophagectomy.

[Mediastinoscopic diagnosis and drainage of pericardial diverticulum--a case report].

A 38-year-old male was suspected of having an enlarged pretracheal lymph node on chest CT scan. At mediastinoscopy, a cystic lesion was recognized, and showed repeated dilatation and contraction synchronously with the cardiac beat. Pneumopericardium was demonstrated by intraoperative pneumocystography. The cystic lesion was diagnosed as pericardial diverticulum. The diverticular wall was partially resected for drainage of the pericardial fluid. Mediastinoscopy as a less invasive procedure may be useful for the differential diagnosis of adenopathies, and in case of lesion such as a small pericardial diverticulum may allow treatment.

[A case of cerebral venous angioma detected by slow velocity-encoding phase contrast MRA: appropriate determination of velocity encode].

We report a 86-year-old woman who has been diagnosed as cerebral venous angioma by slow velocity-encoding phase contrast magnetic resonance angiography (MRA). She had developed headache for one month. T1- and T2-weighted images showed a flow void sign in the right cerebellum with gadolinium enhancement. MRA using time-of-flight sequence revealed no abnormal vascular structures. Conventional phase contrast MRA (velocity encode, 40 or 60 cm/sec) did not disclose obvious vascular abnormalities. However, slow velocity-encoding (20 cm/sec) phase contrast MRA demonstrated a well-demarcated venous angioma in the right transverse sinus. Our results of MRAs suggest that velocity encode is a crucial factor for detection of venous angioma on phase contrast MRA. Slow velocity-encoding phase contrast MRA is a beneficial tool for evaluation of venous malformations, such as venous angioma.

[Mediastinoscopic drainage for descending necrotizing mediastinitis].

A case of descending necrotizing mediastinitis that was treated by mediastinoscopic drainage is reported. The patient was a 56-year-old diabetic woman. A hypopharyngeal abscess extended to the mediastinum through the neck. No septic condition was noted. Chest CT showed that the abscess reached 4 cm below the tracheal bifurcation. Pus was drained under direct observation by mediastinoscopy, and a drain was placed in an appropriate position. After operation, lavage was performed through the drain, and cure was achieved on the 42nd postoperative day. This technique should be considered as surgical treatment for descending necrotizing mediastinitis in the absence of serious complication such as sepsis, because it has a more reliable drainage effect than the conventional transcervical method, and because it is less invasive than thoracotomy.

[Mediastinal bronchogenic cyst associated with high serum level of CA19-9--a surgical case report].

We reported a case of mediastinal bronchogenic cyst in a patient with a high serum level of CA19-9. The patient, a 41-year-old man, presented with a complaint of persistent fever. Chest X-ray examination, computed tomography and magnetic resonance imaging showed a subcarinal mass shadow which was diagnosed preoperatively as a bronchogenic cyst. The serum level of CA19-9 was 73 U/ml. The cyst was partially removed via right thoracotomy. Histopathological findings were compatible with bronchogenic cyst. The CA19-9 level in the specimen was 134,00 U/ml. The serum level of CA19-9 decreased to normal postoperatively. The postoperative course was uneventful.

Mediastinoscopic extirpation of mediastinal ectopic parathyroid gland.

We report a case of a 50-year-old man with hyperparathyroidism secondary to chronic renal failure who underwent extirpation of a mediastinal ectopic parathyroid gland by a transcervical approach under mediastinoscopy. This procedure provides an excellent approach to the mediastinal ectopic parathyroid gland, and is less invasive than median sternotomy or thoracotomy.

Improvement of rat liver graft function by insulin administration to donor.

BACKGROUND & AIMS: The nutritional status of a donor is considered to be an important factor affecting organ viability. The purpose of the present study was to examine hepatic energy status in connection with posttransplantation liver function. METHODS: The following five groups of donor rat livers were prepared and stored in University of Wisconsin solution at 4 degrees C: fasted group, rats fasted for 24 hours; fed group, rats provided standard laboratory chow; fed plus insulin group, fed rats treated with insulin before harvest; fasted plus insulin group, fasted rats treated with insulin before harvest; and fed plus glucagon group, fed rats pretreated with glucagon. RESULTS: Hepatic levels of adenosine triphosphate and total adenine nucleotides were maintained in the decreasing order of the fed plus insulin, fed, fasted plus insulin, fasted, and fed plus glucagon groups during preservation. Lactate production rate and fructose 2,6-bisphosphate level increased in the order of the fed plus insulin, fed, fed plus glucagon, fasted, and fasted plus insulin groups. Liver function after transplantation evaluated by the bile flow rate and enzyme leakage was well restored in the fed plus insulin group. CONCLUSIONS: Insulin administration to nutritionally well-supported livers before harvest improved energy metabolism during preservation and liver function after transplantation.

[Mediastinal thoracic duct cyst--a case report].

The patient, a 55-year-old asymptomatic man, was referred to our hospital in October 1995 for further investigation of a chest ++roentogenographic abnormality found during a "physical check-up". His chest X-ray showed a round shadow over the hilus of the left lung. Computed tomography revealed a homogeneous, low density mass bordering the esophagus, vertebral column, left lower pulmonary vein and descending aorta. Roentogenography after swallowing barium sulfate showed that the esophagus was compressed and displaced to the right in the anterior direction. Endoscopic ultrasound scan demonstrated a cystic mass. The preoperative findings were suggestive of an esophageal cyst or a thoracic duct cyst. On December 12, 1995, the patient was operated on. The mass was 2 x 3 x 6 cm in size, and was easily separated from the left pulmonary vein, esophagus and vertebral column by blunt and sharp dissection, but it was strongly adhered to the aorta. The wall of the cyst was incised and a chylous fluid was found inside. The mass was diagnosed as a thoracic duct cyst and was removed after clipping and cutting the thoracic duct above and below the cyst. Histopathological features of the wall of the cyst was that the luminal surface was lined by a monolayer of flat endothelium and composed of loose fibrous tissue with scattered bundles of smooth muscle. It differed from that of veins. The postoperative course was uneventful and he was discharged on the 12th postoperative day. Mediastinal thoracic duct cysts are rare and only 25 operated cases have been reported in the literature. We review and discuss these cases.

Hepatic segmentectomy on primary liver cancer with situs inversus totalis.

We present the first case treated by hepatic segmentectomy in a 69-year-old woman with primary liver cancer and situs inversus totalis. The situs inversus did not cause any technical problems during the operation, which was conducted under guidance of intraoperative ultrasonography.

New method for measuring ICG Rmax with a clearance meter.

The maximal removal rate of indocyanine green (ICG Rmax) is considered to be an important parameter of hepatic function. However, the method of analysis has some flaws, and an abnormal value is obtained for about 15% of patients. We developed a new method of measuring the ICG Rmax with a clearance meter (RK-1000) that continuously measured the ICG concentration using a fingertip optical sensor. Twenty patients were examined. The histologic diagnosis was as follows: normal for 10, cirrhosis in 6, hepatitis in 4. The ICG concentration was measured in vivo continuously with the RK-1000. To obtain the Rmax by the Michaelis-Menten model, the ICG concentration in the VLDL compartment was subtracted from the values obtained by the RK-1000 because ICG binds to various serum proteins and its rate of removal in the VLDL compartment differs from that in other protein compartments. The removal velocity was calculated and a Michaelis plot obtained. Then Rmax was calculated from the reciprocal of the y-intercept of a Lineweaver-Burk plot. The Rmax in subjects with liver disease was significantly lower than in those with normal liver. It is concluded that our new method of measuring ICG Rmax with the RK-1000 reflects liver function appropriately.

Changes in biliary glutathione level during ischemia-reperfusion of rat liver.

Changes in hepatic and biliary glutathione levels were studied in rat liver treated with tert-butyl hydroperoxide (t-BuOOH) and subjected to ischemia-reperfusion. Immediately after t-BuOOH administration, the oxidized glutathione (GSSG) values and reduced glutathione (GSSG/GSH) ratio in the bile increased dose-dependently and then returned to control level within 10 min, whereas the hepatic ATP level and bile flow rate were not affected by t-BuOOH at doses of up to 1.0 mmol/kg. These data suggested that the liver remains viable on treatment with up to 1.0 mmole/kg t-BuOOH, and that hepatocytes can rapidly dismute t-BuOOH at up to this dose. The hepatic GSH and GSSG levels did not vary appreciably during ischemia for 10 or 30 min or during subsequent reperfusion, but the GSSG/GSH ratio increased after ischemia for 30 min. The rate of bile flow and the biliary level of GSH decreased after ischemia for 30 min in proportion to the decrease in the hepatic ATP level. However, the biliary GSSG concentration did not vary on reperfusion, although GSSG secretion into the bile is also related to the hepatic ATP level. As a result, the GSSG/GSH ratio in the bile increased during reperfusion after ischemia for 30 min. This increased ratio is thought to reflect oxidation of hepatic GSH by hydroperoxide produced during reperfusion. The GSSG/GSH ratio in the bile after 30 min ischemia corresponded to that observed after a small dose (0.07 mmole/kg body wt) of t-BuOOH, which hepatocytes could dismute rapidly without loss of their viability.(ABSTRACT TRUNCATED AT 250 WORDS)

Simultaneous surgery for coronary artery disease and gastric cancer.

Of 26 patients who underwent both coronary artery bypass grafting and abdominal surgery at our institution between 1977 and 1992, nine had severe coronary artery disease associated with UICC stage I gastric cancer. They were treated by coronary artery bypass grafting followed by a curative operation for gastric cancer; the initial four patients underwent two-staged surgery (group A), and the most recent five patients underwent simultaneous surgery (group B). The cardiac surgery was performed first in all patients, and in group A the interval between the two procedures was 2 to 7 weeks. There were no significant differences between the two groups in terms of preoperative characteristics: sex, age, preoperative complications, NYHA class, prior myocardial infarction, ejection fraction, cardiac index, number of vessels diseased, or number of grafts. There were no significant differences between the two groups in terms of blood loss during the gastric operation (A: 649 +/- 194 ml; B: 842 +/- 326 ml) or the operating time (A: 371 +/- 106 minutes; B: 343 +/- 46 minutes). Two group A patients had postoperative complications (one had arrhythmia, and one died of sepsis caused by sutural insufficiency). On the other hand, four group B patients had complications (three cases of transient hyperbilirubinemia and one case of postoperative bleeding; none died). The postoperative hospital stay after gastrectomy was not prolonged in group B compared with group A (A: 41.7 +/- 22.7 days; B: 46.0 +/- 25.0 days). In conclusion, simultaneous procedure of coronary artery bypass grafting and gastric surgery can be performed safely, although careful management is indispensable.

Radical resection of primary malignant melanoma of the gallbladder with multiple metastases: report of a case.

We present herein an usual case of primary malignant melanoma of the gallbladder in a 51-year-old man in whom an exploratory laparotomy for melena revealed six malignant melanoma lesions located in the gallbladder, main pancreatic duct, stomach, duodenum, jejunum, and a mesenteric lymph node. Total pancreatectomy was performed and histologically, junctional activity was seen only in the gallbladder, suggesting that this was the primary site. No melanotic lesions were found on the skin or eyes. The metastases to the main pancreatic duct and gastrointestinal tract appeared likely to have occurred as a consequence of the mucosal dissemination of the tumor cells shed into the bile. The post-operative course was uneventful and combined chemotherapy was administered for 16 months. No new metastatic lesions were found until 21 months postoperatively, when metastases were detected in the brain and thoracic spinal cord. These metastatic tumors were removed surgically, but the patient died from cerebral disturbance 26 months after the initial operation. Thus, we consider that aggressive surgical therapy was effective for extending the survival time and improving the quality of life of this patient.