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.

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.

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.

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.

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.

Hydrolysis and esterification of acylglycerols and analogs in aqueous medium catalyzed by microbial lipases.

The stereoselectivity of microbial lipases from Chromobacterium viscosum (CVL) and Rhizopus arrhizus (RAL) towards monoacylglycerols (rac-1(3)-oleoylglycerol and 2-oleoylglycerol), diacylglycerols (1,3-dioleoylglycerol and rac-1,2(2,3)-dioleoylglycerol) and 2-O-ether analogs (rac-1(3)-oleoyl-2-O-hexadecylglycerol and rac-1(3)-octanoyl-2-O-hexadecylglycerol) was determined. The results of the hydrolysis of 2-O-ether analogs confirmed the importance of the substituent at C-2 of acylglycerols in the stereoselective recognition by microbial lipases and also showed that acylation of mono- and diradylglycerols with oleic acid overlaps the hydrolysis reaction in aqueous medium. With the short-chain, water-soluble octanoic acid no significant esterification occurred. Using rac-1,2(2,3)-dioleoylglycerol as a substrate for the hydrolysis with RAL and CVL, the appearance of 1,3-dioleoylglycerol and of 1(3)-monooleoylglycerol was demonstrated. The possibility of chemical vs. enzyme-catalyzed isomerization of 1,2-dioleoylglycerol and of 2-oleoylglycerol is discussed.

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.

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.

Coronal renal ultrasound: II.

Coronal renal imaging with ultrasound has a number of advantages over other routine scanning orientations in nephrosonography. In a series of 214 patients coronal transverse but especially longitudinal orientation was found to be superior to other scanning methods. The main advantages were: differentiation between renal cysts and hydronephrosis as well as demonstration of renal lithiasis. This approach also should be used to augment the diagnostic sequence of investigating renal masses.

Cavernosography in diagnosis of penile metastases secondary to bladder cancer.

This is a case report of transitional cell carcinoma of the bladder which metastasized to lymph nodes, bone, and the penis. The penile metastases were demonstrated by cavernosography. Secondary tumors in the penis are rare. They presage a bad prognosis and a rapid demise; the patients survive an average of four months.

Coronal renal ultrasound: I.

With recent advances in ultrasound technology, concomitant improvement in sonographic techniques have been required. Sonographic scanning in coronal orientation, both in transverse but especially in longitudinal direction, has demonstrated a number of advantages over the routine transverse and sagittal scans. Closer correlation with functional anatomy of the kidney, more comprehensive scanning with less inerference from adjacent tissues, and better understanding by the clinician are the most obvious advantages of the coronal approach.

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.

"Pulseless" femoral arteriography.

Direct needle arteriography of "pulseless" femoral arteries is described. The information obtained, and the excellent detail of the arterial tree, is discussed in cases of collateral filling of the femoral artery. Evaluation of occluded by-pass grafts is also mentioned.

False aneurysm of the superior mesenteric artery--a complication of pancreatitis.

Early recognition of pseudocyst formation in pancreatitis has been a very important contribution of diagnostic ultrasound. Furthermore, haemorrhage or abscess formation, an additional complication, can also be suspected by this diagnostic modality. False aneurysm formation of a larger, neighbouring artery is not easily recognized by ultrasound. It is for this reason that this case report is made.

Adrenal incidentalomas--analysis of 23 cases discovered by ultrasound.

Frequent use of abdominal ultrasonography (USG) increases discovery of incidental adrenal tumors. Our experience and concise review of recent opinions on management of adrenal incidentalomas is presented. In four out of 23 patients with adrenal incidentalomas false positivity of USG was found (all on the left side), 4 cases were identified as pseudoadrenal masses. Hormonal activity was proved in 4 out of 15 true adrenal masses (2 pheochromocytomass, 2 aldosteronomas). Five out of 11 hormonally inactive tumors were benign adenomass, 2 myelolipomas, 2 simple cysts, 1 metastasis of bronchogenic carcinoma and 1 tuberculotic involvement. The smallest tumor was aldosteronoma (2 cm in diameter), the largest was myelolipoma (more than 10 cm). Size of benign adenomas ranged between 2.5-4.8 cm. Three main ultrasonic patterns of adrenal tumors were recognized: (1) anechogenic cysts, (2) complex but predominantly hyperechogenic myelolipomas, (3) hypoechogenic all other masses.

Utilization of a tomographic attachment for "moving band" arteriography.

By using a slit plate, scanographic arterial studies can be performed with a tomographic attachment of an X-ray unit that is normally used for routine radiographic examinations. The expense is minimal and no structural changes are necessary.

Recovery room risk and outcome associated with renal extracorporeal shock wave lithotripsy.

STUDY OBJECTIVES: To determine (1) the general risk and outcome in the recovery room among 4 different anesthetic techniques associated with 2 different extracorporeal shock wave lithotripsy (ESWL) machines and (2) any gender-related differences among patients undergoing ESWL. DESIGN: Retrospective statistical analysis. SETTING: University medical center. PATIENTS: 2,203 ASA physical status I-IV patients undergoing ESWL over a 46-month period. INTERVENTIONS: A review of the chart records of patients who received 1 of 4 anesthetic techniques (general, spinal, epidural, or monitored anesthesia care) on 1 of 2 ESWL machines. MEASUREMENTS AND MAIN RESULTS: A positive finding was defined as a complication and/or side effect of such significance as to require a treatment order or recovery room note on the patient's chart. The main complications and/or side effects were nausea and/or vomiting, flank pain, and hypertension. Female patients experienced flank pain and nausea and/or vomiting with general anesthesia and monitored anesthesia care at approximately twice the frequency of males. CONCLUSIONS: (1) Overall, ESWL is relatively safe. Both machine types and all anesthetic techniques exhibited a low risk and good outcome. (2) There appear to be gender-related differences during ESWL. Female and male patients may have different pain and nausea and/or vomiting thresholds during ESWL.

Use of the Augustine stylet anticipating difficult tracheal intubation in Treacher-Collins syndrome.

Treacher-Collins syndrome is a familial and congenital condition often associated with a difficult airway. Although the condition is rare, the anesthesia care provider may encounter it on occasion. This report describes a patient with Treacher-Collins syndrome scheduled to undergo facial reconstruction (fore-head plasty, brow lift, and rhinoplasty) as the sixth of multiple operations. A nasotracheal intubation using the stylet component of a recently introduced airway device, the Augustine Guide, was successfully performed. This is believed to be the first reported use of this method using the Augustine stylet.

Controlling the hemodynamic response to laryngoscopy and endotracheal intubation.

The hemodynamic response to the stress of laryngoscopy and endotracheal intubation does not present a problem for most patients. However, patients with cardiovascular or cerebral disease may be at increased risk of morbidity and mortality from the tachycardia and hypertension resulting from this stress. These hemodynamic effects gained notice after the introduction and use of muscle relaxants, such as curare and succinylcholine, for endotracheal intubation at the time of anesthesia induction. A variety of anesthetic techniques and drugs are available to control the hemodynamic response to laryngoscopy and intubation. The method or drug of choice depends on many factors, including the urgency and length of surgery, choice of anesthetic technique, route of administration, medical condition of the patient, and individual preference. The possible solutions number as many as the medications and techniques available and depend on the individual patient and anesthesia care provider. This paper reviews these medications and techniques to guide the clinician in choosing the best methods.

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.