Severity of trauma changes expression of TNF-alpha mRNA in the brain of mice

BACKGROUND: The greater nitrogen loss that occurs with increasing severity of trauma is believed to occur because activation of the hypothalamus-pituitary axis is greater with severe injury. Cytokines in the brain stimulate the hypothalamus-pituitary-adrenal axis. This study was carried out to investigate whether the brain would recognize severity of trauma via TNF-alpha mRNA synthesis in the brain. METHODS: Male C57BL/6 mice (n = 70, BW: 20-28 g) were randomly assigned into four groups, (1) control (no anesthesia or incision), (2) anesthesia alone, (3) anesthesia plus laparotomy by short incision (short), and (4) anesthesia plus laparotomy by long incision (long). A laparotomy was carried out in the short and long groups by a 1.2-cm vertical incision and by a horizontal plus a vertical incision (2.4 x 2.4 cm), respectively. Exactly either 3 or 24 h after surgery, the animals were decapitated. TNF-alpha mRNA levels in the tissues were determined by semi-quantitative PCR. RESULTS: Nitrogen and catecholamine excretion were increased in the long wound group compared with the short wound group. Expression of TNF-alpha mRNA in the brain was greater in the long group after surgery than in the control, anesthesia, and short groups (brain, long: 0.150 +/- 0.005; P < 0.01 vs control, anesthesia alone, and short groups), but TNF-alpha levels in the plasma were the same in the short and long groups after surgery. CONCLUSION: Levels of TNF-alpha mRNA in the brain were enhanced according to the length of the wound probably because of greater neural stimuli from the wound site, and this elevation was involved in the greater nitrogen loss.     

Intraoperative management of heart transplantation in Japan--report of two cases

We experienced intraoperative anesthetic management of two cases of heart transplantation in Japan. Both patients were in the end stage of cardiac failure due to dilated cardiomyopathy. One patient had had implantation of left ventricular assist system, and another patient had had implantation of automated cardioveter defibrillator. Transesophageal echocardiography was useful for the monitoring of cardiac function during the operation. Anti-arrythmic therapy including heart pacing and protection of right heart failure are important for the circulatory management of heart transplantation. The anesthesiologist is needed not only for the management of respiration and circulation but also for the prevention of infection and control of the time schedule.     

Efficacy of hand-assisted laparoscopic surgery (HALS) in older adult patients (≥80 years) with primary colorectal cancer

BackgroundFrom 2004 to 2014, 821 colorectal cancer primary resections were conducted at our institution. Of these, 102 patients (12.4%) were older adults over 80 years old. underwent either the conventional laparotomy group (72 patients) or the hand-assisted laparoscopic surgery (HALS) group (30 patients).MethodsData were extracted for 102 patients over 80 years old who underwent primary resection for colorectal cancer and were divided into two groups: conventional laparotomy (CL) (n=72) and hand-assisted laparoscopy (n=30). Pre-operative characteristics and outcomes were compared.ResultsBaseline characteristics were similar between groups, except for age: CL group median 83.5 years old (range, 80–92 years old) and hand-assisted laparoscopy (HALS) group median 81.5 years old (range, 80–88 years old) (P=0.027). Pre-operative cardiac and lung function risk, performance status, and pathological classification stage (pStage) were almost similar between groups (P=0.668, P=0.176, P>0.999, P=0.217). No significant differences were found for operation time. The HALS group resulted in less blood loss (median 204 mL in the CL group and median 68 mL in the HALS group, P=0.003), shorter postoperative hospital stay (median was 18 days in the CL group and median was 12 days in the HALS group, P<0.001), and fewer postoperative wound infections (18 cases in the CL group and 2 cases in the HALS group, P=0.034). Five-year relapse-free survival (5Y-RFS) was 48.1% in the CL group and 73.3% in the HALS group (P=0.028). Five-year overall survival (5Y-OS) was 48.2% in the CL group and 73.3% in the HALS group (P=0.027).ConclusionsApproximately 70% of surgical treatment for patients over 80 years old with colorectal carcinoma were performed by CL. However, HALS had significant advantages including less blood loss, fewer wound infections, and shorter hospital stays. Therefore, HALS could proactively be considered to older adult patients with colorectal cancer.     

Involvement of DNase II-like acid DNase in the cataract formation of the UPL rat and the Shumiya cataract rat

The loss of organelles and DNA is important to ensure transparency of the lenses, and DNase II-like acid DNase (also called DNase IIbeta, DLAD) is related to the loss of organelles and DNA in the lenses. We investigated the relation between the degradation of DNA and DLAD mRNA expression in the lenses of two hereditary cataract rats, the UPL rat (UPLR) and the Shumiya cataract rat (SCR), during cataract development. Undigested DNA was detected in the lens cortexes of normal UPLRs and SCRs, and undigested DNA was degraded in the lens nuclei of normal UPLRs and SCRs. DLAD does not affect common cataract formation, since DLAD mRNA expression levels in the lenses of cataractous SCRs were not changed with an increase in age, and undigested DNA was degraded in the lens nuclei of cataractous SCRs. On the other hand, an accumulation of undigested DNA was found in the lens nuclei of cataractous UPLRs at 46 and 53 d of age with opaque lenses, and the decrease in DLAD mRNA expression levels occurred prior to the accumulation of undigested DNA in the lens nuclei. It is possible that UPLRs are a good model for cataract caused by a decrease of DNA degradation in the lenses.     

Effects of naloxone on the cough depressant activities of antitussive drugs

Effects of naloxone on the cough depressant action of antitussive drugs were investigated in pentobarbital anesthetized male and female cats. Respiration and cough reflex were measured using a pneumotachograph via a cannula inserted into the trachea. The cough reflex was elicited by electrical stimuli to the superior laryngeal nerve. An i.v. administration of morphine (1 mg/kg) significantly inhibited the cough reflex for at least 60 min. The antitussive effect of morphine was antagonized by naloxone (400 micrograms/kg). The inhibitory effect of morphine on the respiratory frequency was also antagonized by naloxone. The cough reflex was significantly inhibited by fominoben (5 mg/kg, i.v.) and dextromethorphan (3 mg/kg, i.v.). However, the respiratory frequency was increased by these two drugs. An i.v. administration of naloxone prevented the antitussive effects and the excitatory effects in respiratory frequency of fominoben and dextromethorphan. The present study suggests that the cough depressant actions of antitussive drugs may be mediated by endogenous opiates and/or by neurotransmitters which are modified by endogenous opiates.     

A preliminary study for clinical pharmacokinetics of oral fluorine anticancer medicines using the commercial MRI system 19F-MRS

These preliminary studies of dynamic natural abundance 19F-magnetic resonance spectroscopy (19F-MRS) on 5-FU based medicines were performed in the human liver using commercial 1.5 T MRI equipment. A single tuned, custom-made circular shape surface coil with a diameter of 15 cm operating at 60 MHz was used for the 19F-MRS study. Localized proton shimming with a whole body coil was performed with adequate volume to include the observing area of the surface coil, and the line width of the water signal was less than 40 Hz. Very different spectroscopic appearance patterns of 5-FU were observed. We examined whether the pharmacokinetics in the liver of orally administered 1-hexylcarbamoyl-5-fluorouracil (HCFU) differ from those of orally administered 5'-deoxy-5-fluorouridine (5'-DFUR). This preliminary study suggested the 19F-MRS technique could be a useful method of evaluating in vivo the metabolism of 5-FU based medicines.     

Specific IgE for wheat in tear fluid of patients with allergic conjunctivitis

Context: Allergy to hydrolyzed wheat protein in facial soap has become a major social issue in Japan. It has been reported that the most frequent early symptoms of allergy to hydrolyzed wheat protein in soap are allergic conjunctivitis and rhinitis, while wheat-dependent exercise-induced anaphylaxis can be induced by long-term use.

Objective: We evaluated the relation between tear fluid levels of specific IgE for wheat and the features of allergic conjunctivitis.

Methods: A prospective, non-randomized, cross-sectional study was conducted in 103 patients with moderate to severe allergic conjunctivitis (allergic group) and 20 age- and sex-matched healthy control subjects (control group). Specific IgE for wheat was measured in tear fluid with an immunochromatography assay, and a skin prick test (SPT) was also performed. Symptoms (sneezing, rhinorrhea, nasal obstruction, ocular itching, and lacrimation) were assessed in each subject along with the activities of daily living (ADL) score and the total ocular symptom score for allergic conjunctivitis. A severity score (0, 1, 2, or 3) was assigned for various changes of the palpebral and bulbar conjunctiva, as well as for limbal and corneal lesions associated with allergic conjunctivitis.

Results: The IgE positive rate and specific IgE score were both higher in the allergic group than in the control group (71.8% versus 40.0% and 1.9?±?0.7 versus 1.4?±?0.5). A positive SPT for wheat was also more frequent in the allergic group than in the control group (6.8% versus 0.0%). Within the allergic group, patients with a positive SPT had higher specific IgE scores than patients with a negative SPT (3.3?±?0.5 versus 1.8?±?0.6, p?r?=?0.665), tearing (r?=?0.672), and the total ocular symptom score (r?=?0.204). Wheat IgE in tear fluid was also correlated with the severity of rhinitis symptoms, including sneezing (r?=?0.610), nose blowing (r?=?0.640), and nasal obstruction (r?=?0.677). Furthermore, the tear fluid wheat IgE score was correlated with five objective features of allergic conjunctivitis (p?Conclusions: These results suggest that wheat allergy may be involved in the development of allergic conjunctivitis.     

Demonstration of donor specific unresponsiveness in rat islet allografts: importance of transplant site for induction by cyclosporin A and maintenance

Summary The purpose of the present study was to evaluate the effects of transplant site (the liver via the portal vein vs the renal subcapsular space) on islet allograft survival using cyclosporin A and also to determine whether or not the unresponsiveness obtained is donor specific and how the site selected is related to the maintenance of unresponsiveness. Prolongation of islet allograft survival (WKA/Qdj:RT1^u Lewis:RT1¹) was obtained by using hand-picked clean fresh islets as donors and by s. c. administration of cyclosporin A (30 mg/kg, day 0, 1, 2) when the islets were transplanted into the liver. Eleven out of 15 recipients were normoglycaemic for more than 90 days after transplantation (control mean survival time: 4.4±1.1 days, n=5). However, all the renal subcapsular grafts were rejected within 18 days after transplantation. Two normoglycaemic recipients bearing intrahepatic grafts were challenged with full-thickness donor-strain (WKA/Qdj) skin grafts at 120 days after the islet transplantation. Both recipients became diabetic and the skin grafts rejected within 16 days. The nine normoglycaemic recipients were made diabetic again with streptozotocin (40 mg/kg) between 90 and 120 days after the initial islet transplantation. Re-transplants of fresh donor-strain (WKA/Qdj) islets into the liver (n=3) in the absence of cyclosporin A maintained normoglycaemia in the recipients for more than 60 days, whereas re-transplants of donor-strain islets beneath the kidney capsule were rejected within 20 days. Intrahepatic re-transplants of third party grafts (PVG/c: RT1^c:) (n=3) were rejected after seven days. These findings clearly demonstrate that the donor specific unresponsiveness in rat islet allografts was not only induced but also maintained only when the liver was the site used for implantation of the islets.