Dexmedetomidine vs. propofol sedation reduces the duration of mechanical ventilation after cardiac surgery - a randomized controlled trial.

OBJECTIVE: The aim of our study was to compare the clinical effects of sedation with dexmedetomidine vs. propofol in patients undergoing cardiac surgery and analyze their effects on the duration of mechanical ventilation (MV), length of stay in the intensive care unit (ICU), and total hospital stay. PATIENTS AND METHODS: The study included 120 patients who were randomized in a 1:1 ratio into two groups of 60 patients. The first group was sedated with continuous dexmedetomidine in doses 0.2-0.7 mcg/kg/h. The second group was sedated with propofol in doses 1-2 mg/kg/h. RESULTS: Patients sedated with dexmedetomidine required 2.2 hours less time on MV (p<0.001). There was a positive correlation between the duration of MV and the ICU length of stay (r=0.368; p<0.001), as well as between the duration of MV and the total hospital stay (r=0.204; p=0.025). Delirium occurred in the postoperative period in 25% of patients sedated with propofol, while in the dexmedetomidine group it was only 11.7% (p=0.059). Patients who developed delirium had a significantly longer duration of MV (12.6±5.4 vs. 9.3±2.5 hours, p=0.010). CONCLUSIONS: Postoperative sedation with dexmedetomidine, compared to propofol, reduces the duration of MV, but does not influence the length of stay in the ICU and length of hospitalization after open heart surgery.

The presence of pyruvate carboxylase in the human brain and its role in the survival of cultured human astrocytes.

Pyruvate carboxylase (PC) is a mitochondrial, biotin-containing enzyme catalyzing the ATP-dependent synthesis of oxaloacetate from pyruvate and bicarbonate, with a critical anaplerotic role in sustaining the brain metabolism. Based on the studies performed on animal models, PC expression was assigned to be glia-specific. To study PC distribution among human neural cells, we probed the cultured human astrocytes and brain sections with antibodies against PC. Additionally, we tested the importance of PC for the viability of cultured human astrocytes by applying the PC inhibitor 3-chloropropane-1,2-diol (CPD). Our results establish the expression of PC in mitochondria of human astrocytes in culture and brain tissue and also into a subpopulation of the neurons in situ. CPD negatively affected the viability of astrocytes in culture, which could be partially reversed by supplementing media with malate, 2-oxoglutarate, citrate, or pyruvate. The provided data estimates PC expression in human astrocytes and neurons in human brain parenchyma. Furthermore, the enzymatic activity of PC is vital for sustaining the viability of cultured astrocytes.

Plasma levels of glial cell marker S100B in children with autism.

Autism spectrum disorder (ASD) is a neurodevelopmental condition with increasing incidence. Recent evidences suggest glial cells involvement in autism pathophysiology. S100B is a calcium binding protein, mainly found in astrocytes and therefore used as a marker of their activity. In our study, children with autism had higher plasma concentrations of S100B compared to non-autistic controls. No association of S100B plasma levels with behavioral symptoms (ADI-R and ADOS-2 scales) was found. Plasma S100B concentration significantly correlated with urine serotonin, suggesting their interconnection. Correlation of plasma S100B levels with stool calprotectin concentrations was found, suggesting not only brain astrocytes, but also enteric glial cells may take part in autism pathogenesis. Based on our findings, S100B seems to have a potential to be used as a biomarker of human neurodevelopmental disorders, but more investigations are needed to clarify its exact role in pathomechanism of autism.

How viruses infiltrate the central nervous system.

Central nervous system is protected by the blood-brain barrier, which represents a physical, metabolic and transport barrier and is considered to be a part of a highly dynamic system termed neurovascular unit. Several pathogens, among them viruses, are able to invade the brain. Traversal of viruses across the blood-brain barrier is an essential step for the invasion of the central nervous system and can occur by different mechanisms - by paracellular, transcellular and/or by "Trojan horse" pathway. Penetration of viruses to brain can lead to the blood-brain barrier dysfunction, including increased permeability, pleocytosis and encephalopathy. Viruses causing the central nervous system infections include human immunodeficiency virus type 1, rhabdovirus, different flaviviruses, mouse adenovirus type 1, herpes simplex virus, influenza virus, parainfluenza virus, reovirus, lymphocytic choriomeningitis virus, arbovirus, cytomegalovirus, mumps virus, parvovirus B19, measles virus, human T-cell leukemia virus, enterovirus, morbillivirus, bunyaviruses, togaviruses and others. In this review we summarized what is known about the routes of how some viruses enter the brain and how neurons and glial cells react to infection.

Lichen planus induced by carbamazepine: a case report.

We report a case of Lichen planus in a female patient who has been treated for epilepsy in the Referral Center for Epilepsy of the Ministry of Health of the Republic of Croatia. She was diagnosed with mesio-temporal lobe epilepsy with secondary generalization and had been treated for years with carbamazepine. In Novemeber 2009, erythematous papulosquamous papules were noticed on her trunk and under her breasts which spread to her legs. Dermatohistological testing confirmed the diagnosis of Lichen planus. Replacement of carbamazepine with oxcarbazepine and application of steroid therapy resulted in regression of skin changes.

Derivatives of pyrimidine, phthalimide and anthranilic acid as inhibitors of human hydroxysteroid dehydrogenase AKR1C1.

Human hydroxysteroid dehydrogenase (HSD) AKR1C1 is a member of the aldo-keto reductase superfamily, and it functions mainly as a 20alpha-HSD. It catalyzes the reduction of the potent progesterone to the weak 20alpha-hydroxyprogesterone, and of 3alpha,5alpha-tetrahydroprogesterone (5alpha-THP; allopregnanolone) to 5alpha-pregnane-3alpha,20alpha-diol. AKR1C1 thus decreases the levels of progesterone and 5alpha-THP in peripheral tissue. Progesterone inhibits cell proliferation, stimulates differentiation of endometrial cells, and is also important for maintenance of pregnancy, while 5alpha-THP allosterically modulates the activity of the gamma-aminobutyric acid receptor. Inhibitors of AKR1C1 are thus potential agents for treatment of endometrial cancer and endometriosis, as well as other diseases like premenstrual syndrome, catamenial epilepsy and depressive disorders.We have synthesized a series of pyrimidine, phthalimido and athranilic acid derivatives, and have here examined their inhibitory properties towards AKR1C1. A common aldo-keto reductase substrate, 1-acenaphthenol, was used to monitor the NAD(+)-dependent oxidation catalyzed by AKR1C1. The most potent inhibitors of AKR1C1 were the pyrimidine derivative N-benzyl-2-(2-(4-methoxybenzyl)-6-oxo-1,6-dihydropyrimidin-4-yl)acetamide (K(i)=17 microM) and the anthranilic acid derivative 2-(((2',3-dichlorobiphenyl-4-yl)carbonyl)(methyl)amino)benzoic acid (K(i)=33 microM), both of which are non-competitive inhibitors.

A randomized, double-blind, close-ranging, pilot study of intravenous granisetron in the prevention of postoperative nausea and vomiting in patients abdominal hysterectomy.

BACKGROUND AND OBJECTIVE: Postoperative nausea and vomiting (PONV) is a frequent and unpleasant experience that may increase postoperative complications and costs. For surgical procedures with a high risk of PONV, prevention is preferable to treatment. In this study, the authors explore the dose-response relationship between granisetron administered just prior to the end of surgery and post-operative nausea and vomiting in patients undergoing abdominal hysterectomy. METHODS: This was a randomized, double-blind, placebo-controlled, pilot study of post-operative nausea and vomiting prevention. Patients undergoing elective open abdominal hysterectomy requiring general anaesthesia received a single dose of granisetron 0.1, 0.2 or 0.3 mg or placebo administered approximately 15 min prior to the end of surgery. The primary efficacy end-point was the proportion of patients with no vomiting in the 0--6 h interval following medication administration. No inferential statistics were planned. RESULTS: The proportion of patients with no vomiting episode in the 0--6 h interval after administration of study medication was higher in each granisetron treatment group (>90%) than in the placebo group (77%). Proportions of patients with no vomiting episodes in the 0--24 h interval were similar across treatment groups. Results of analyses of proportions of patients with no moderate or severe nausea episodes, proportions of those requiring rescue medication and times to first use of rescue medication suggested a treatment effect of granisetron relative to placebo in both the 0--6 and 0--24 h intervals. Similar proportions of patients in each treatment group reported at least one adverse event. CONCLUSIONS: Granisetron at doses of 0.1, 0.2 and 0.3 mg administered just prior to the end of surgery suggested a trend of improved efficacy compared to placebo in preventing postoperative nausea and vomiting in the first 6 h after abdominal hysterectomy. This pilot study did not identify a dose-response relationship.

Diagnostic microarray: an array of possibilities for parasitology.

Parasites affect a majority of the world's population. Despite this fact, dreams of developing vaccines remain far off. Scientists have long studied gene expression as a hallmark of gene activities reflecting current cell conditions. Analyzing differentially expressed genes is a major initiative, and most labs recoil at the amount of time and high costs required obtaining results. By employing microarrays, researchers can decrease their reliance upon time consuming techniques; consequently, microarray is beginning to dominate other molecular diagnostic technologies. Moreover, the ability of microarrays to monitor simultaneous gene expression of thousands of genes and to produce broad arrays of data has the potential to shift the resources of the scientists from data gathering to analyzing data that are already available. As microarray technology improves and its cost decreases, the role of ability to "see" the molecular biology pathways involved in parasite host relationships will place this technology at the forefront of parasite research.

Self-tolerance in the immune privileged CNS: lessons from the entorhinal cortex lesion model.

Upon peripheral immunization with myelin epitopes, susceptible rats and mice develop T cell-mediated demyelination similar to that observed in the human autoimmune disease multiple sclerosis (MS). In the same animals, brain injury does not induce autoimmune encephalomyelitis despite massive release of myelin antigens and early expansion of myelin specific T cells in local lymph nodes, indicating that the self-specific T cell clones are kept under control. Using entorhinal cortex lesion (ECL) to induce axonal degeneration in the hippocampus, we identified possible mechanisms of immune tolerance after brain trauma. Following ECL, astrocytes upregulate the death ligand CD95L, allowing apoptotic elimination of infiltrating activated T cells. Myelin-phagocytosing microglia express MHC-II and the costimulatory molecule CD86, but lack CD80, which is found only on activated antigen presenting cells (APCs). Restimulation of invading T cells by such immature APCs (e.g. CD80 negative microglia) may lead to T cell anergy and/or differentiation of regulatory/Th3-like cells due to insufficient costimulation and presence of high levels of TGF-beta and IL-10 in the CNS. Thus, T cell -apoptosis, -anergy, and -suppression apparently maintain immune tolerance after initial expansion of myelin-specific T lymphocytes following brain injury. This view is supported by a previous metastatistical analysis which rejected the hypothesis that brain trauma is causative of MS (Goddin et al., 1999). However, concomitant trauma-independent proinflammatory signals, e.g., those evoked by clinically quiescent infections, may trigger maturation of APCs, thus shifting a delicate balance from immune tolerance and protective immune responses to destructive autoimmunity.

Comparison of nicardipine versus placebo to control hemodynamic responses during emergence and extubation.

OBJECTIVE: To compare 2 different doses of intravenous nicardipine versus placebo to control heart rate and blood pressure responses to emergence and extubation. DESIGN: Prospective, randomized, double-blind, placebo-controlled. SETTING: University hospital, single-institutional. PARTICIPANTS: Forty-five American Society of Anesthesiologists (ASA) class I through III adult patients. INTERVENTIONS: General endotracheal anesthesia was with oxygen and isoflurane and muscle relaxation. At the end of surgery, with at least 2 twitches present by nerve stimulator and end-tidal isoflurane <0.4%, reversal was accomplished with neostigmine and glycopyrrolate. Two minutes post-reversal, the study drug (nicardipine, 0.015 mg/kg; nicardipine, 0.03 mg/kg; or a saline placebo) was given. Heart rate and blood pressure were measured for every minute up to 10 minutes and at 15 minutes postreversal. MEASUREMENTS AND MAIN RESULTS: There were no significant differences among groups in age, gender, ASA class, weight, or heart rate. The nicardipine groups, 0.015 and 0.03 mg/kg, had lower blood pressure values than the placebo group. There was a significant difference in blood pressure among groups, with greater and more consistent attenuation of blood pressure occurring with the larger nicardipine dose. There were no episodes of hypotension or adverse events. CONCLUSIONS: Compared with placebo, both nicardipine doses attenuated blood pressure but not heart rate responses during emergence and extubation. Greater blood pressure control occurred with the larger nicardipine dose of 0.03 mg/kg.

Turnover of rat brain perivascular cells.

Brain perivascular spaces harbor a population of cells which exhibit high phagocytic capacity. Therefore, these cells can be labeled by intraventricular injection of tracers. Such perivascular cells at the interface between blood and brain are believed to belong to the monocyte/macrophage lineage and to be involved in antigen presentation. Currently, it is unclear whether these cells undergo a continuous turnover by entering and leaving the bloodstream. Using bone-marrow-chimeric animals, migration of donor macrophages into brain perivascular spaces has been reported. On the other hand, following intracerebral injection of india ink into nontransplanted animals, ink-labeled perivascular cells were still found 2 years after injection, suggesting a high stability of this cell pool. Thus, the turnover of perivascular cells observed in chimeras might be a result of bone marrow transplantation rather than a physiological occurrence. To address this issue, we monitored de novo invasion of macrophages into perivascular spaces of apparently healthy adult rats by applying techniques other than bone marrow transplantation, (i) consecutive injections of different tracers and (ii) ex vivo isolation of macrophages from the blood, cell labeling, and reinjection into the same animal to avoid MHC mismatch. Both approaches revealed vivid de novo invasion of macrophages into perivascular spaces, but not into brain parenchyma, rendering untenable the concept of perivascular cells forming a stable population of macrophages in the brain. Thus, brain perivascular spaces are under permanent immune surveillance of blood borne macrophages in normal adult rats.

Immune surveillance of mouse brain perivascular spaces by blood-borne macrophages.

Virchow-Robin's perivascular spaces lie between the basement membrane around pericytes and the basement membrane at the surface of the glia limitans of the brain vessels. They are directly connected to the subpial space and harbour a population of cells distinct from pericytes, perivascular microglia and other cells within perivascular spaces (e.g. T cells and mast cells) in their ability to quickly phagocytose particles from the cerebrospinal fluid (CSF). Morphology, function, and cell surface proteins of these perivascular cells suggest an origin from the monocyte/macrophage lineage. It is currently unclear to what extent these brain perivascular cells represent a resident population of histiocytes or undergo continuous supplementation from blood monocytes. Using transplants of green-fluorescent-protein (GFP)-transfected bone marrow cells, we therefore investigated the replacement of perivascular cells by blood-borne macrophages in adult mice. GFP-positive cells in the perivascular spaces were found as early as 2 weeks post transplantation. The substitution of host perivascular cells by donor-derived macrophages was then evaluated using immunocytochemistry and intraventricular injection of hydrophilic rhodamine-fluorescent tracers. Such tracers diffuse along perivascular spaces and are subsequently phagocytosed by perivascular cells leading to stable phagocytosis-dependent labelling. Thus, the population of newly immigrated macrophages could be related to the total number of perivascular macrophages. This approach revealed a continuous increase of donor-derived perivascular cells. At 14 weeks post transplantation, all perivascular cells were donor-derived. These data show that brain perivascular cells are a population of migratory macrophages and not resident histiocytes.

[Treatment of ascites with reinfusion of ascitic fluid concentrate]. / Liecba ascitu reinfúziou ascitického koncentrátu.

Ascites which is refractory to common therapeutical measures is a great problem. It deteriorates patient's life and is a sign of poor prognosis. Different methods of peritoneal fluid reinfusion belong to effective non-pharmaceutical therapeutic approaches. Main target of this study was to analyse the effectiveness and safety of peritoneal fluid reinfusion and to compare two methods of its administration (i.v. reinfusion and intraperitoneal reinfusion). During three years we have performed 97 reinfusions in 4 patients (2 women and 2 men; mean age 56 years). I.v. reinfusion was administered 68 times and intraperitoneal ewinfusion was performed 28 times. Usually we evacuated 8000 ml of ultrafiltrate. The most common complications were haemoperitoneum (6x) and short-term chills (2x). We didn't have any complications such as coagulopathy, peritonitis or circulation collapse. Intraperitoneal administration seems to be more advantageous when compared with i.v. application, because of less frequent detection of fibrin degradation products and D-dimers after the procedure and higher diuresis during the following days. (Tab. 2, Fig. 5, Ref. 13.).

Dolasetron for the prevention of postoperative nausea and vomiting following outpatient surgery with general anaesthesia: a randomized, placebo-controlled study. The Dolasetron PONV Prevention Study Group.

In a multicentre, randomized, double-blind, placebo-controlled dose-ranging study, 1030 patients undergoing outpatient surgery with general anaesthesia received i.v. dolasetron mesylate (12.5, 25, 50, or 100 mg) or placebo. The principal outcome measure was the proportion of patients who were free of emesis or rescue medication for the 24-h period after the study drug was given; the subsidiary outcome measure was survival time without rescue medication. Effects on nausea were quantified using a visual analogue scale. Compared with placebo, a complete response was significantly higher when all four dolasetron doses were combined (49% vs. 58%, P =0.025). In females, dolasetron, 12.5-mg, dolasetron provided maximum clinical benefit (effectiveness compared with adverse events), with no additional benefit in complete response rates or nausea visual analogue scale scores at higher doses. No significant differences were observed in complete response for any dolasetron dose in males compared with placebo. The majority of adverse events reported were mild or moderate. Dolasetron provided well-tolerated, safe, and effective prophylaxis for post-operative nausea and vomiting with maximum effectiveness observed at a dose of 12.5 mg.

Pooled analysis of three large clinical trials to determine the optimal dose of dolasetron mesylate needed to prevent postoperative nausea and vomiting. The Dolasetron Prophylaxis Study Group.

STUDY OBJECTIVE: To identify the maximally effective dolasetron dose (i.e., maximum efficacy with minimum adverse events) for prevention of postoperative nausea and vomiting (PONV) using the statistical power generated in a pooled patient sample from three large, nearly identical clinical trials. DESIGN: Three randomized, multicenter, placebo-controlled, double-blinded trials. SETTING: Trials 1, 2, and 3 enrolled patients at 10, 25, and 17 hospitals and/or surgical centers, respectively. PATIENTS: A total of 1,946 ASA physical status, I, II, and III patients. Trials 1 and 2 enrolled only female patients (n = 916) undergoing gynecologic surgery. Trial three enrolled 722 females (approximately 70% gynecologic surgeries) and 308 males (approximately 46% orthopedic surgeries) undergoing a variety of surgical procedures. INTERVENTIONS: All surgical procedures used balanced general anesthesia. Patients received 12.5, 25, 50, or 100 mg of the antiemetic, dolasetron, near the end of anesthesia. MEASUREMENTS AND MAIN RESULTS: Efficacy endpoints were identical and measured for 24 hours: complete response (no vomiting or rescue medication) and maximum nausea, reported using a 100-mm visual analog scale (VAS). Safety was assessed using adverse event reports, laboratory and electrocardiographic data, and vital signs. All four dolasetron doses produced significant increases in complete response and decreases in maximum VAS nausea compared with placebo (p < 0.01). No increased efficacy was observed with dolasetron doses higher than 12.5 mg. Safety was similar between each dolasetron dose and placebo. CONCLUSION: Dolasetron 12.5 mg, given near the end of anesthesia, is the maximally effective dose studied for preventing postoperative nausea and vomiting.

Prevention and treatment of postoperative nausea and vomiting.

Pain, nausea and vomiting are frequently listed by patients as their most important perioperative concerns. With the change in emphasis from an inpatient to outpatient hospital and office-based medical/surgical environment, there has been increased interest in the 'big little problem' of postoperative nausea and vomiting (PONV). Currently, the overall incidence of PONV is estimated to be 25 to 30%, with severe, intractable PONV estimated to occur in approximately 0.18% of all patients undergoing surgery. PONV can lead to delayed postanaesthesia care unit (PACU) recovery room discharge and unanticipated hospital admission, thereby increasing medical costs. The aetiology and consequences of PONV are complex and multifactorial, with patient-, medical- and surgery-related factors. A thorough understanding of these factors, as well as the neuropharmacology of multiple emetic receptors [dopaminergic, muscarinic, cholinergic, opioid, histamine, serotonin (5-hydroxy-tryptamine; 5-HT)] and physiology [cranial nerves VIII (acoustic-vestibular), IX (glossopharyngeal) and X (vagus), gastrointestinal reflex] relating to PONV are necessary to most effectively manage PONV. Commonly used older, traditional antiemetics for PONV include the anticholinergics (scopolamine), phenothiazines (promethazine), antihistamines (diphenhydramine), butyrophenones (droperidol) and benzamides (metoclopramide). These antiemetics have adverse effects such as dry mouth, sedation, hypotension, extrapyramidal symptoms, dystonic effects and restlessness. The newest class of antiemetics used for the prevention and treatment of PONV are the serotonin receptor antagonists (ondansetron, granisetron, tropisetron, dolasetron). These antiemetics do not have the adverse effects of the older, traditional antiemetics. Headache and dizziness are the main adverse effects of the serotonin receptor antagonists in the dosages used for PONV. The serotonin receptor antagonists have improved antiemetic effectiveness but are not as completely efficacious for PONV as they are for chemotherapy-induced nausea and vomiting. Older, traditional antiemetics (such as droperidol) compare favourably with the serotonin receptor antagonists regarding efficacy for PONV prevention. Combination antiemetic therapy improves efficacy for PONV prevention and treatment. In the difficult-to-treat PONV patient (as in the chemotherapy patient), suppression of numerous emetogenic peripheral stimuli and central neuroemetic receptors may be necessary. This multimodal PONV management approach includes use of: (i) multiple different antiemetic medications (double or triple combination antiemetic therapy acting at different neuroreceptor sites); (ii) less emetogenic anaesthesia techniques; (iii) adequate intravenous hydration; and (iv) adequate pain control.

Efficacy of repeat intravenous dosing of ondansetron in controlling postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled multicenter trial.

STUDY OBJECTIVES: To compare repeat intravenous (i.v.) dosing of ondansetron 4 mg with placebo for the treatment of postoperative nausea and vomiting (PONV) in patients for whom prophylactic, preoperative ondansetron 4 mg i.v. was inadequate DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Ten outpatient surgical centers in the United States. PATIENTS: 2,199 male and female ASA physical status I, II, and III patients > or = 12 years old scheduled to undergo outpatient surgical procedures and receive nitrous oxide-based general anesthesia. INTERVENTIONS: Ondansetron 4 mg i.v. was administered to all patients before induction of general anesthesia. Patients who experienced PONV or requested antiemetic therapy within 2 hours after discontinuation of inhaled anesthesia were randomized (1:1) to either a repeat i.v. ondansetron 4 mg dose or placebo. MEASUREMENTS AND MAIN RESULTS: Of the 2,199 patients prophylactically treated with ondansetron 4 mg before anesthesia induction, 1,771 (80.5%) did not experience PONV or request antiemetic therapy during the 2 hours following discontinuation of anesthesia. Of the 428 patients who experienced PONV or requested antiemetic therapy during the same period, and were randomized to additional treatment (214 randomized to ondansetron, 214 randomized to placebo), the incidence of complete response (no emesis, no rescue medication, no study withdrawal) was similar for both ondansetron-randomized and placebo-randomized groups for the 2-hour (34% and 43%, respectively, p = 0.074) and 24-hour (28% and 32%, respectively, p = 0.342) postrandomization study periods. Repeat ondansetron dosing was not more effective than placebo in controlling either postoperative emesis or the severity/duration of postoperative nausea. The administration of an additional dose of ondansetron 4 mg postoperatively did not result in an increased incidence of adverse effects. CONCLUSIONS: In patients for whom preoperative prophylaxis with ondansetron 4 mg i.v. is not successful, a repeat dose of ondansetron 4 mg i.v. in the postanesthesia care unit does not appear to offer additional control of PONV.

Reduced resource utilization in patients treated for postoperative nausea and vomiting with dolasetron mesylate. MCPR44 Study Group.

STUDY OBJECTIVE: To compare the effect of four different increasing increasing intravenous (i.v.) doses of dolasetron mesylate (12.5 mg, 25 mg, 50 mg, and 100 mg) versus placebo on resource utilization in patients who experienced and were treated for postoperative nausea and vomiting (PONV). DESIGN: Prospective, double-blind, randomized, multicenter study. PATIENTS: 620 ASA physical status I, II, and III male and female outpatients scheduled for surgery with general anesthesia. INTERVENTIONS: Patients who experienced postoperative nausea (duration > or = 5 min, self-reported as moderate to severe) or vomiting (> or = 1 emetic episode) within 2 hours of arrival in the postanesthesia care unit (PACU) were given a single i.v. dose of dolasetron mesylate (12.5 mg, 25 mg, 50 mg, or 100 mg) or placebo infused for at least 30 seconds. MEASUREMENTS AND MAIN RESULTS: Resource utilization in the PACU was assessed by time spent by nurses and/or doctors with patients for PONV and the use of hospital resources such as patient/bed linens and staff/emesis supplies. A significantly (p < 0.05) lower proportion of dolasetron-treated patients compared to placebo-treated patients required new patient/bed linens and staff/emesis supplies. Patients in the placebo group required the greatest amount of care from nurses and/or doctors compared to patients receiving dolasetron. CONCLUSIONS: Treatment with dolasetron can significantly decrease the utilization of emesis supplies and other hospital resources, including staff/emesis supplies and patient/bed linens. In addition, patients receiving dolasetron used fewer health care resources in time spent by hospital personnel than patients who were not treated with dolasetron.

Stereoselectivity of Mucorales lipases toward triradylglycerols--a simple solution to a complex problem.

The lipases from Rhizopus and Rhizomucor are members of the family of Mucorales lipases. Although they display high sequence homology, their stereoselectivity toward triradylglycerols (sn-2 substituted triacylglycerols) varies. Four different triradylglycerols were investigated, which were classified into two groups: flexible substrates with rotatable O'-C1' ether or ester bonds adjacent to C2 of glycerol and rigid substrates with a rigid N'-C1' amide bond or a phenyl ring in sn-2. Although Rhizopus lipase shows opposite stereopreference for flexible and rigid substrates (hydrolysis in sn-1 and sn-3, respectively), Rhizomucor lipase hydrolyzes both groups of triradylglycerols preferably in sn-1. To explain these experimental observations, computer-aided molecular modeling was applied to study the molecular basis of stereoselectivity. A generalized model for both lipases of the Mucorales family highlights the residues mediating stereoselectivity: (1) L258, the C-terminal neighbor of the catalytic histidine, and (2) G266, which is located in a loop contacting the glycerol backbone of a bound substrate. Interactions with triradylglycerol substrates are dominated by van der Waals contacts. Stereoselectivity can be predicted by analyzing the value of a single substrate torsion angle that discriminates between sn-1 and sn-3 stereopreference for all substrates and lipases investigated here. This simple model can be easily applied in enzyme and substrate engineering to predict Mucorales lipase variants and synthetic substrates with desired stereoselectivity.

[Pathology of the spleen in ultrasonographic imaging]. / Patológia sleziny v ultrasonografickom obraze.

Authors provide review on diffuse and focal splenic lesions, traumatic injuries, contribution of ultrasonography in staging of malignant lymphomas and ultrasound-guided percutaneous biopsy. Special attention is given to the question of normal spleen size and diagnosis of splenomegaly. In 230 patients (98 males) aged 18-72 years (median 34.2) witch underwent complex preventive examination, maximal longitudinal diameter (LDmax) of the spleen were measured. Using linear regression analysis relation of spleen size and body high, weigh and body mass index (BMI) was evaluated. Median LDmax was 10.1 cm, range 7.8-13.5 cm. As a reference limit authors accept 95% confidence interval of median: 7.9-12.3 cm. Statistically significant correlation (p < 0.01, r = 0.31) between LDmax and body high was found out. Ultrasonography because of diagnostic efficiency is suggested the method of choice in diagnosing pathologic involvement of the spleen.