Stability of Adrenaline in Irrigating Solution for Intraocular Surgery.

Intraocular irrigating solution containing 1 µg/mL adrenaline is widely used during cataract surgery to maintain pupil dilation. Prepared intraocular irrigating solutions are recommended for use within 6 h. After the irrigating solution is admistered for dilution, the adrenaline may become oxidized, and this may result in a decrease in its biological activity. However, the stability of adrenaline in intraocular irrigating solution is not fully understood. The aim of this study was to evaluate the stability of adrenaline in clinically used irrigating solutions of varying pH. Six hours after mixing, the adrenaline percentages remaining were 90.6%±3.7 (pH 7.2), 91.1%±2.2 (pH 7.5), and 65.2%±2.8 (pH 8.0) of the initial concentration. One hour after mixing, the percentages remaining were 97.6%±2.0 (pH 7.2), 97.4%±2.7 (pH 7.5), and 95.6%±3.3 (pH 8.0). The degradation was especially remarkable and time dependent in the solution at pH 8.0. These results indicate that the concentration of adrenaline is decreased after preparation. Moreover, we investigated the influence of sodium bisulfite on adrenaline stability in irrigating solution. The percentage adrenaline remaining at 6 h after mixing in irrigating solution (pH 8.0) containing sodium bisulfite at 0.5 µg/mL (concentration in irrigating solution) or at 500 µg/mL (concentration in the undiluted adrenaline preparation) were 57.5 and 97.3%, respectively. Therefore, the low concentration of sodium bisulfite in the irrigating solution may be a cause of the adrenaline loss. In conclusion, intraocular irrigation solution with adrenaline should be prepared just prior to its use in surgery.

Injury due to extravasation of thiopental and propofol: Risks/effects of local cooling/warming in rats.

Inadvertent leakage of medications with vesicant properties can cause severe necrosis in tissue, which can have devastating long-term consequences. The aim of this study was to evaluate the extent of extravasation injury induced by thiopental and propofol, and the effects of cooling or warming of local tissue on extravasation injury at macroscopic and histopathologic levels. Rats were administered intradermally thiopental (2.5 mg/100 µL) or propofol (1.0 mg/100 µL). Rats were assigned randomly to three groups: control (no treatment), cooling and warming. Local cooling (18-20 °C) or warming (40-42 °C) was applied for 3 h immediately after agent injection. Lesion sizes (erythema, induration, ulceration, necrosis) were monitored after agent injection. Histopathology was evaluated in skin biopsies taken 24 h after agent injection. Thiopental injection induced severe skin injury with necrosis. Peak lesions developed within 24 h and healed gradually 18-27 days after extravasation. Propofol induced inflammation but no ulceration, and lesions healed within 1-2 days. Local cooling reduced thiopental- and propofol-induced extravasation injuries but warming strongly exacerbated the skin lesions (e.g., degeneration, necrosis) induced by extravasation of thiopental and propofol. Thiopental can be classified as a "vesicant" that causes tissue necrosis and propofol can be classified as an "irritant". Local cooling protects (at least in part) against skin disorders induced by thiopental and propofol, whereas warming is harmful.

Cholangiocyte senescence caused by lysophosphatidylcholine as a potential implication in carcinogenesis.

BACKGROUND: The incidence of biliary tract cancer in patients with pancreaticobiliary maljunction or intrahepatic cholelithiasis is markedly high with undefined mechanism. In these diseases, biliary lysophosphatidylcholine (LPC) level is reportedly increased. This study investigated the influence of LPC on cholangiocytes focusing on cellular senescence and its potential contribution to carcinogenesis. METHODS: Cultured MMNK-1, an immortalized human cholangiocyte was treated with LPC in vitro and its effect was evaluated. RESULTS: Lysophosphatidylcholine demonstrated cytotoxicity with generation of intracellular reactive oxygen species. Accordingly, LPC provoked oxidative DNA injury, whereas the gene expressions of DNA repair enzyme (OGG1, MUTYH, MTH1) remained unchanged. Interestingly, LPC caused global DNA hypomethylation, which is frequently observed in cancer tissues. Microarray analysis identified differentially regulated genes in response to LPC, which included the components of senescence-associated secretory phenotype (SASP) including interleukin-8 (IL-8), IL-6, transforming growth factor-ß and plasminogen activator inhibitor-1. Significant induction of these genes was further confirmed by quantitative real-time polymerase chain reaction. In addition to upregulation of p21 gene expression, senescence-associated beta-galactosidase activity, a widely used marker of cellular senescence was significantly induced by the treatment of LPC. CONCLUSIONS: Based on these data, cholangiocyte senescence and SASP caused by LPC are potential pathogenic mechanisms in the development of biliary tract cancer.

[The necessity for pharmaceutical education on perioperative care -- considering the activities of operating room pharmacists in relation to types of anesthetic operations involved].

In an effort better to understand the application of pharmaceutical services in the operating room (OR) we conducted a survey among OR department directors of 526 hospitals throughout Japan. A total of 202 directors responded to the survey. Pharmacists are expected to achieve better outcomes in pharmacotherapy as well as play major roles as members of diverse perioperative care teams. Besides implementing medication safety standards, pharmacists' roles include optimizing drug therapy and other clinical interventions, both in OR and wards. Presently, few pharmacists in Japan participate in perioperative care, which is one of the reasons that the majority of pharmacy schools in Japan have been providing fewer lectures or rotations related to perioperative care. Yet, developing general perioperative management as another crucial role OR pharmacists play and incorporating it into pharmaceutical education would be important. Enriching perioperative care provided by pharmacists can contribute toward improving clinical competence in these professionals.

Evaluation of corneal damage caused by iodine preparations using human corneal epithelial cells.

PURPOSE: To compare the cytotoxicity of povidone-iodine solution (PVP-I) with that of polyvinyl alcohol-iodine solution (PAI) for ophthalmic use. METHODS: Cells of the human corneal epithelial cell line HCE-T were exposed to various dilutions of PVP-I or PAI, and the cytotoxicity of these two antiseptics was evaluated. The relative toxicities of PVP-I and PAI were also investigated following the inactivation of iodine by achromatization with sodium thiosulfate. RESULTS: PVP-I and PAI had equivalent antiseptic effects, but the cytotoxicity of PVP-I diluted 16-fold was higher than that of PAI diluted 6-fold. Following inactivation of iodine with sodium thiosulfate, the cytotoxicity of PVP-I remained concentration dependent, whereas PAI exhibited a low toxicity that was similar to the effect of saline on cell viability. Exposure to lauromacrogol, a surfactant used in PVP-I, in solution at concentrations of 1-1000 mg/mL clearly resulted in corneal cytotoxicity. The PVP-I and PAI solutions had a pH value of 4.0 and 5.2, respectively. HCE-T cells were significantly more viable at pH 7 than at pH 1-6. CONCLUSION: To avoid corneal damage, preoperative antisepsis of the surgical field should be accomplished with PAI diluted 6-fold, rather than with PVP-I diluted 16-fold. The toxicity of the iodine compound stems primarily from the available iodine concentration and partly from its pH, surfactant and osmolality. Further clinical investigations are required in order to determine the optimal concentrations for use.

Partial characterization of proapoptotic action of biliary deteriorated lipids on biliary epithelial cells in pancreaticobiliary diseases.

BACKGROUND: Lysophosphatidylcholine (LPC), a derivative of phosphatidylcholine (PC) hydrolyzed by phospholipase A2 (PLA2), is reported to be increased in bile of the patients with pancreaticobiliary maljunction or intrahepatic cholelithiasis, both of which are major risk factors for biliary tract cancers with undefined etiology. METHODS: To investigate the influence of LPC on biliary epithelial cells (BECs), a human cholangiocarcinoma cell line HuCCT-1 and an immortalized human BECs line MMNK-1 were treated by LPC in vitro. RESULTS: The treatment of LPC exhibited cytotoxicity with significant induction of apoptosis. In addition to upregulation of Fas receptor mRNA, the activities of caspase-8 and -3 were significantly increased by LPC treatment. We also observed upregulation of Bax mRNA and significant activation of caspase-9. Interestingly, LPC significantly upregulated G2A, a member of transmembrane G protein-coupled receptor family at mRNA and protein levels, and 9-hydroxyoctadecaduenoic acid (9HODE), an oxidized free fatty acid that functions as a ligand for G2A dramatically reduced cell viability when treated together with LPC. CONCLUSIONS: These data suggest that PLA2, which catalyzes the hydrolysis of PC to yield LPC and free fatty acid, is supposed to be an important etiological factor in BECs injury in pancreaticobiliary maljunction or intrahepatic cholelithiasis.

The mechanisms of insulin secretion and calcium signaling in pancreatic ß-cells exposed to fluoroquinolones.

Fluoroquinolones reportedly induce hypoglycemia through stimulation of insulin secretion from pancreatic ß-cells via inhibition of K(ATP) channels and activation of L-type voltage-dependent Ca(2+) channels. In physiological condition, the cytosolic Ca(2+) concentration ([Ca(2+)](c)) is also regulated by release of Ca(2+) from intracellular Ca(2+) stores. In this study, we investigated the mechanism of insulin secretion induced by fluoroquinolones, with respect to intracellular Ca(2+) stores. Even where the absence of supplemental extracellular Ca(2+), insulin secretion and [Ca(2+)](c) were increased by gatifloxacin, levofloxacin or tolbutamide. Insulin secretion and the rise of [Ca(2+)](c) induced by fluoroquinolones were reduced by depleting of Ca(2+) in endoplasmic reticumum (ER) by thapsigargin, and inhibiting ryanodine receptor of ER by dantrolene. Inhibition of inositol 1,4,5-triphosphate receptor of ER by xestospongin C suppressed insulin secretion induced by fluoroquinolones, whereas it did not affect [Ca(2+)](c). Destruction of acidic Ca(2+) stores such as lysosome and lysosome-related organelles by glycyl-L-phenylalanine-2-nephthylamide (GPN) did not affect insulin secretion and the rise of [Ca(2+)](c) induced by fluoroquinolones. The increase in insulin and [Ca(2+)](c) induced by tolbutamide were reduced by thapsigargin, dantrolene, and GPN but not by xestospongin C. In conclusion, fluoroquinolones induces Ca(2+) release from ER mediated by the ryanodine receptor, and the reaction might involve in insulin secretion. Sulfonylureas induce Ca(2+) release from GPN-sensitive acidic Ca(2+) stores, but fluoroquinolones did not.

Effects of 3-O-methyldopa, L-3,4-dihydroxyphenylalanine metabolite, on locomotor activity and dopamine turnover in rats.

It has been well known that 3-O-methyldopa (3-OMD) is a metabolite of L-3,4-dihydroxyphenylalanine (L-DOPA) formed by catechol O-methyltransferase (COMT), and 3-OMD blood level often reaches higher than physiological level in Parkinson's disease (PD) patients receiving long term L-DOPA therapy. However, the physiological role of 3-OMD has not been well understood. Therefore, in order to clarify the effects of 3-OMD on physiological function, we examined the behavioral alteration in rats based on locomotor activity, and measured dopamine (DA) and its metabolites levels in rats at the same time after 3-OMD subchronic administration. The study results showed that repeated administrations of 3-OMD increased its blood and the striatum tissue levels in those rats, and decreased locomotor activity in a dose dependent manner. Although 3-OMD subchronic administration showed no significant change in DA level in the striatum, DA metabolite levels, such as 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and homovanillic acid (HVA) were significantly decreased. After 3-OMD washout period (7 d), locomotor activity and DA turnover in those rats returned to normal levels. Furthermore, locomotor activity and DA turnover decreased by 3-OMD administration were recovered to normal level by acute L-DOPA administration. These results suggested that 3-OMD affect to locomotor activity via DA neuron system. In conclusion, 3-OMD itself may have a disadvantage in PD patients receiving L-DOPA therapy.

Influences of pyrexia and age on theophylline clearance in young children with asthma.

Fifty hospitalized children with asthmatic bronchitis and bronchial asthma were treated with a continuous intravenous drip infusion of aminophylline. To investigate the pharmacokinetics of theophylline in the presence of pyrexia, patients were divided into two groups based on body temperature: a pyrexia group (> or = 38 degrees C) and a non-pyrexia group (< 38 degrees C). Theophylline clearance was 0.064 +/- 0.017 liters/kg/hr in the non-pyrexia group and 0.049 +/- 0.010 liters/kg/hr in the pyrexia group. Theophylline clearance in the non-pyrexia and pyrexia groups was 0.044 +/- 0.007 liters/kg/hr and 0.030 +/- 0.009 liters/kg/hr (< or = 6 months), 0.071 +/- 0.011 liters/kg/hr and 0.047 +/- 0.008 liters/kg/hr (6 to < or = 12 months), 0.084 +/- 0.012 liters/kg/hr and 0.055 +/- 0.006 liters/ kg/hr (1 to < or = 2 years), and 0.065 +/- 0.007 liters/kg/hr and 0.051 +/- 0.001 liters/kg/hr (2 to < or = 3 years), respectively. In all age groups, theophylline clearance of the pyrexia group was significantly less than that of the non-pyrexia group (p < 0.01), showing that there was a significant pharmacokinetic difference in theophylline clearance between the groups. Multivariate statistical analysis showed that theophylline clearance was affected by pyrexia and age. This study showed that the presence of pyrexia decreases theophylline clearance, and that it affects theophylline clearance in an age-dependent manner. Based on the results of this study, dosages should be designed based on the clearance at the time of pyrexia.

[The role of the pharmacist in the management of the operating room].

Pharmacy services have traditionally consisted of dispensing, provision of drug information and inventory management practices. Pharmacist's impact on the implementation of medication safety standards, drug therapy optimization, and other clinical interventions has been adequately reviewed in settings of general wards and considered as standard practice; however, these activities in the operating room have not become the standard practice. In this article, we reviewed the clinical interventions by pharmacists working in the operating room. The five main duties or obligations required of the pharmacists are appropriate drug management, achieving medical economic benefits, mixing injectable drugs, risk management, and provision of drug information. The major information provided to physicians and nurses is on usage, dosage, stability, incompatibility, pharmacological effects and adverse effects. Physicians and nurses require the drug information provided by the pharmacist in the operating room. Furthermore, their requirement for the stationing of pharmacist is extremely high. It is suggested that these services might be quite important in optimizing drug therapy and preventing adverse effects. Additionally, pharmacist can contribute on rational use of drug, safety management, reduction of works of other medical staff, and also the medical economics through pharmaceutical care in operating room as well as in general wards. It is suggested that stationing pharmacists in the operating room might be indispensable for hospital administration in view of the medication safety and cost reduction.

Relationship between 3-O-methyldopa and the clinical effects of entacapone in advanced Parkinson's disease.

The aim of this study is to clarify the relationship between serum 3-O-methyldopa (3-OMD) and the clinical effects of entacapone. The 3-OMD and maximum serum concentration (Cmax) of levodopa were measured in 21 Parkinson's Disease patients who took 100 mg levodopa / dopa decarboxylase inhibitor. After the administration of entacapone, the 3-OMD concentration and percentage of "on" time during waking hours (% of "on" time) were studied for 8 weeks. The 3-OMD concentration was reduced by 34%, and the increase in % of "on" time was 28% at the 8th week compared with baseline. We defined the COMT-index as [baseline 3-OMD concentration] / [levodopa Cmax when 100 mg levodopa was administered alone]. The COMT-index was significantly correlated with the increase in % of "on" time at the 8th week. In conclusion, the measurement of baseline 3-OMD and levodopa pharmacokinetics is useful for predicting the clinical effects of entacapone.

Timolol activates the enzyme activities of human carbonic anhydrase I and II.

Timolol, a beta-blocker, has been shown to be an effective ocular hypotensive agent when used alone or with carbonic anhydrase inhibitor on ocular hypertensive or open angle glaucoma patients. The effect of timolol hemihydrate on the CO(2) hydration activities of human carbonic anhydrase (HCA) I and II and their reaction mechanisms were investigated. Timolol activates the enzyme activities of HCA I and HCA II. In HCA I and II, the enzyme kinetic results clearly showed that timolol increases the value of V(max) but does not influence the value of K(m). The enzyme kinetic method showed that timolol noncompetitively activates HCA I and II activities through the formation of a ternary complex consisting of the enzyme, the substrate, and timolol. These results indicate that timolol binds apart from the narrow cavity of the active site. AutoDocking results showed that timolol binds at the entrance of the active site cavity in a region where the proton shuttle residue, His 64, of HCA I or II, is placed. The enzyme kinetic and AutoDocking results showed that timolol might weakly bind near the proton shuttle residue, His 64, to accelerate the proton transfer rate from His 64 to the buffer components. It is known that efficient activators of carbonic anhydrase possess a bulky aromatic/heterocyclic moiety and a primary/secondary amino group in their molecular structure. Timolol has a heterocyclic moiety and a secondary amino group, which are typical structures in efficient activators of carbonic anhydrase.

Bile alcohols function as the ligands of membrane-type bile acid-activated G protein-coupled receptor.

TGR5 is a G protein-coupled receptor that is activated by bile acids, resulting in an increase in cAMP levels and the subsequent modulation of energy expenditure in brown adipose tissue and muscle. Therefore, the development of a TGR5-specific agonist could lead to the prevention and treatment of various metabolic disorders related to obesity. In the present study, we evaluated the ability of bile alcohols, which are structurally and physiologically similar to bile acids and are produced as the end products of cholesterol catabolism in evolutionarily primitive vertebrates, to act as TGR5 agonists. In a cell-based reporter assay and a cAMP production assay performed in vitro, most bile alcohols with a side chain containing hydroxyl group(s) were highly efficacious agonists for TGR5 comparable to its most potent ligand in the naturally occurring bile acid, lithocholic acid. However, the abilities of the bile alcohols to activate TGR5 varied with the position and number of the hydroxyl substituent in the side chain. Additionally, the conformation of the steroidal nucleus of bile alcohols is also important for its activity as a TGR5 agonist. Thus, we have provided new insights into the structure-activity relationships of bile alcohols as TGR5 agonists.

Structure-activity relationship of bile alcohols as human farnesoid X receptor agonist.

FXR (farnesoid X receptor) is a bile acid-activated nuclear receptor that regulates not only the biosynthesis and enterohepatic circulation of bile acids, but also triglyceride, cholesterol and glucose metabolism. FXR-mediated signaling pathways have become promising novel drug targets for the treatment of common metabolic and hepatic diseases. With the aim of uncovering novel modulators of FXR and further elucidating the molecular basis of FXR activation, we investigated the structure-activity relationships of a variety of naturally occurring sterols structurally related to bile acids in terms of their FXR agonist activity. Here, we report that the ability of bile alcohols to activate FXR varied with the position and number of hydroxyl groups existing in the steroid side chain of bile alcohols. In addition, we showed that the shortening of the steroid side chain of bile acids as well as bile alcohols resulted in a decline of the ability of these agents to activate FXR. Thus, we provide new insights into the structure-activity relationships of bile acids and bile alcohols as FXR agonists.

[Immunization of pharmacy students in Japan].

We conducted a survey on the immunization requirements of the students in the fourth year of the 4-year-course departments of pharmacy in Japan by using a self-administered questionnaire, which was mailed to the directors of the institutes. Of the 61 departments invited, 54 responded. Program of seroprevalence examination or vaccination was not in place against measles, rubella, mumps and varicella, and hepatitis B in 31.5% (17/54), 53.7% (29/54), 57.4% (31/54), and 68.5% (37/54), respectively. Surveillance of the history of infection and vaccination was carried out in 21 departments, but only 5 departments insisted on documented evidence of immunity. Students who were proven to be susceptible to these diseases were required to receive immunization in most departments that performed seroprevalence examination. Seroprevalence examination was carried out in colleges in 83.3% (25/30), and the expenses were born by department in 70.0% (21/30). On the other hand, vaccination was carried out in colleges in 30.0% (9/30), and the expenses were born by department in 6.7% (2/30). Of the 54 departments, 29, 11, and 3 departments executed these programs in the 3rd year, 4th year, and at the time of admission, respectively. Influenza vaccination during the year of clinical clerkship and tuberculosis skin test was required in 20.4% (11/54) and 37.0% (20/54), respectively; these were carried out in the colleges in 8 and 19 departments and the expenses were born by department in 1 and 18 departments, respectively. Countermeasures against these infectious diseases were found to be insufficient in most departments of pharmacy.

[Effect of the admixture of tetracycline and nadifloxacin ointments on their stability and their antibacterial activity].

Impetigo contagiosa staphylogenes is commonly treated by administering a combination of nadifloxacin and tetracycline ointments. However, it is not clear whether nadifloxacin and tetracycline are stable after mixing. The purpose of this study was to evaluate the stability of these agents in combination. We also evaluated changes in antibacterial activity after mixing. Mixing the two ointments caused tetracycline to change from yellow to brown in the admixture. Furthermore, the tetracycline content in the ointment decreased in a time-dependent manner, to about 40% at 288 h after mixing. In addition, the nadifloxacin content in the ointment did not change 288 h after mixing. In an alkaline environment (pH 9.0 and 11.0), the tetracycline content decreased and the color of tetracycline changed to brown. These results suggest that sodium hydroxide, which is an additive in nadifloxacin ointment, influences the content of tetracycline. We evaluated the chemical sensitivity of Staphylococcus aureus using disk tests. Nadifloxacin and tetracycline ointment showed the largest radius of inhibition circle, followed by the admixture 0 h after mixing and the admixture 72 h after mixing. These results suggest that the antibacterial activity is inhibited by the admixture. We propose that pharmacists should avoid mixing nadifloxacin with tetracycline ointment in the treatment of impetigo contagiosa staphylogenes and should take care to avoid interactions caused by additives in the ointments.

The mechanisms by which latanoprost free acid inhibits human carbonic anhydrase I and II.

Latanoprost, a prostaglandin F2 alpha analogue, has been shown to be an effective ocular hypotensive agent when used alone on ocular hypertensive or open angle glaucoma patients. Carbonic anhydrase (CA) inhibitors are also used to reduce ocular hypertension by decreasing aqueous humor secretion, and are given in combination with prostaglandin F2 alpha analogue. It has been shown that prostaglandin F2 alpha, Minprostin F2 alpha, has been shown to increase the carbonic anhydrase (CA) activity and blood pressure. However, the effects of latanoprost on CA have not been clarified. Therefore, we studied the effects of latanoprost free acid on human carbonic anhydrase (HCA) I and II using the stopped flow method. Latanoprost free acid inhibited the hydration activity of HCA I or II by a noncompetitive mechanism. The inhibition constants (Ki) of latanoprost free acid for HCA I and II were 0.22 and 2.3 mM, respectively. Therefore, latanoprost free acid is a weak inhibitor of HCA I or II. AutoDock simulation of the latanoprost free acid-HCA I or II complex showed that the carboxylic moiety of latanoprost free acid, which is located at the end of the molecule, binds to the zinc ion of the active site by stretching of the chain of latanoprost free acid through the narrow and deep active site cavity of HCA I or II. In the active site cavity of HCA I or II, one side is hydrophilic and the other is hydrophobic. AutoDock simulation results clearly showed that latanoprost free acids lie down on the hydrophobic sides of the active site cavities in HCA I and II. The noncompetitive inhibition mechanism and the binding mode of latanoprost free acid indicate that the behavior of latanoprost free acid is very similar to that of simple anions.

Detoxication treatment for carbamazepine and lithium overdose.

This article reports detoxication treatments of a case of combined overdose of carbamazepine and lithium in a 38-year-old female with bipolar disorder. She was brought to the emergency unit after the family found her unresponsive and lying near empty packages for carbamazepine (corresponded to 7.7 g) and lithium carbonate (corresponded to 6.6 g) tablets. On admission, her blood pressure, heart rate and respiratory rate were 80/55 mmHg, 90 per minute and 13 per minute, respectively. Her GCS was 3 (E1, M1, V1). She received gastric lavage after intratracheal intubation, followed by administration of activated charcoal via gastric tube, and a large volume (800 ml/h) of lactate Ringer's solution by intravenous infusion. The serum levels of carbamazepine and lithium approximately 5 h after ingestion were 56.0 mug/ml and 3.56 mEq/l, respectively. The carbamazepine overdose was mainly treated by a 3 h charcoal hemoperfusion (CHP). The CHP treatment decreased serum carbamazepine levels by approximately 30-40% as compared with the levels simulated by Bayesian analysis using 1-point or 2-points serum level(s) (without detoxication treatment). For lithium overdose continuous infusion of Ringer's solution was effective, which increased serum sodium gradually and facilitated the elimination of lithium. In conclusion, the treatments with CHP and continuous infusion of Ringer's solution were considered to be effective for detoxification of carbamazepine and lithium overdose, respectively, when compared with those drug levels without detoxication treatment that simulated by Bayesian analysis method.

[Influence of tacrolimus and ciprofloxacin on glucose metabolism].

Tacrolimus is an immunosuppressive drug that causes glucose intolerance. On the other hand, ciprofloxacin, which is widely used in the treatment of infectious diseases, is known to cause hypoglycemia as a side effect. We investigated the effects of tacrolimus and ciprofloxacin on serum glucose and insulin levels in rats, as well as on insulin secretion and the viability of HIT-T15 cells. The rats received intraperitoneal injections of tacrolimus and/or ciprofloxacin for 1 week, and their arterial blood was sampled after the administration of glucose. HIT-T15 cells were cultured in the presence of tacrolimus and/or ciprofloxacin, and the insulin level in the supernatant was measured. Ciprofloxacin did not show a significant effect on serum glucose and insulin levels after multiple administrations in the rats. In contrast, rats in the tacrolimus treatment group showed low serum insulin and high serum glucose levels. Moreover, the coadministration of ciprofloxacin and tacrolimus resulted in higher glucose levels compared with tacrolimus alone 0.5 h after glucose stimulation. In addition, we observed that the rats administered tacrolimus and/or ciprofloxacin had low body weight and food intake. Tacrolimus caused a dose-dependent decrease in the viability of the HIT-T15 cells. Furthermore, both drugs were highly toxic to HIT-T15 cells. In contrast, tacrolimus alone and coadministration of the drugs resulted in no significant difference in insulin secretion. These results suggest that the cytotoxic effects of ciprofloxacin and tacrolimus cause a decrease in insulin secretion, leading to glucose intolerance.

Development of a surgical site infection (SSI) surveillance system, calculation of SSI rates and specification of important factors affecting SSI in a digestive organ surgical department.

We have developed an original system to conduct surgical site infection (SSI) surveillance. This system accumulates SSI surveillance information based on the National Nosocomial Infections Surveillance (NNIS) System and the Japanese Nosocomial Infections Surveillance (JNIS) System. The features of this system are as follows: easy input of data, high generality, data accuracy, SSI rate by operative procedure and risk index category (RIC) can be promptly calculated and compared with the current NNIS SSI rate, and the SSI rates and accumulated data can be exported electronically. Using this system, we monitored 798 patients in 24 operative procedure categories in the Digestive Organs Surgery Department of Mazda Hospital, Mazda Motor Corporation, from January 2004 through December 2005. The total number and rate of SSI were 47 and 5.89%, respectively. The SSI rates of 777 patients were calculated based on 15 operative procedure categories and Risk Index Categories (RIC). The highest SSI rate was observed in the rectum surgery of RIC 1 (30%), followed by the colon surgery of RIC3 (28.57%). About 30% of the isolated infecting bacteria were Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Using quantification theory type 2, the American Society of Anesthesiology score (4.531), volume of hemorrhage under operation (3.075), wound classification (1.76), operation time (1.352), and history of diabetes (0.989) increased to higher ranks as factors for SSI. Therefore, we evaluated this system as a useful tool in safety control for operative procedures.