OBJECTIVE

To determine the effect of glutathione S-transferases M1 and T1 polymorphisms on the risk of senile cataract among Egyptians.

BACKGROUND

The glutathione S-transferases (GSTs) are polymorphic enzymes that are important in the protection against oxidative damage.

METHODS

Using a multiplex polymerase chain reaction (PCR), GSTM1 and GSTT1 gene polymorphisms were evaluated in 53 Egyptians with senile cataract and in 73 healthy individuals of the control group.

RESULTS

The frequency of GSTM1-positive individuals among the senile cataract group was significantly higher than in controls. The risk among the GSTM1-positive individuals of developing senile cataract was even higher in females. It is also increased with combination of "GSTM1-positive and GSTT1-positive" genotypes. However the combination of "GSTM1-null, GSTT1-positive" was found to be protective (OR = 0.47; 95 % CI: 0.22-0.99; p = 0.045).

CONCLUSIONS

The GSTMI-positive genotype and the combined "GSTM1-positive/GSTT1-positive" genotype may be associated with an increased risk of development of senile cataract among Egyptians. However, the "GSTM1-null/GSTT1-positive" genotype was found to be protective. Therefore, when evaluating the role of a particular GST gene in disease susceptibility, the whole pattern of different biotransformation enzymes should be taken into account (Tab. 4, Fig. 1, Ref. 36). Full Text (Free, PDF) www.bmj.sk.

As a tension-free repair technique, Lichtenstein operation has gained great popularity worldwide during the last decade. Expert centres do this technique using local anaesthesia in nearly 95 % of cases. However, general anaesthesia is used in many hospitals, while regional anaesthesia is preferred in some centres. To date, no study has compared different types of anesthesia in respect of inflammatory response and oxidative stress specifically. The objective of this prospective study was to compare local, spinal and general types of anesthesia regarding their effects on inflammatory response and oxidative stress in Lichtenstein hernia repair. Lichtenstein hernia repair causes only a mild oxidative stress. While total WBC and neutrophil count responses fade away after 24 hours in patients who are operated under local anaesthesia, these changes in spinal and general types of anaesthesia cases stay valid at 24th hour. Spinal anaesthesia is seen to be more advantageous than local and general types of anaesthesia when C-reactive protein as an acute phase marker is considered. Total antioxidant status shows minor alterations in three types of anaesthesia, however, general anaesthesia seems to be the least reliable among them. Overall, local and spinal anaesthesia methods can be accepted as better alternatives in comparison with general anaesthesia in regard to oxidative stress (Tab. 2, Ref. 25). Full Text (Free, PDF) www.bmj.sk.

In the original version of Table 1 published online, upward arrows to indicate increased translocation of PAMPs were missing from the row entitled 'Translocation' for both the column on alcoholic liver disease and nonalcoholic fatty liver disease. This error has now been updated in the PDF and HTML version of the article.

Great efforts have been directed to the dissection of the cell-autonomous circadian oscillator in Drosophila. However, less information is available regarding how this oscillator controls rhythmic rest-activity cycles. We have identified a viable allele of roundabout, robo(hy), where the period of locomotor activity is shortened. From its role in axon-pathfinding, we anticipated developmental defects in clock-relevant structures. However, robo(hy) produced minor defects in the architecture of the circuits essential for rhythmic behaviour. ROBO's presence within the circadian circuit strengthened the possibility of a novel role for ROBO at this postdevelopmental stage. Genetic interactions between pdf (01) and robo(hy) suggest that ROBO could alter the communication within different clusters of the circadian network, thus impinging on two basic properties, periodicity and/or rhythmicity. Early translocation of PERIOD to the nucleus in robo(hy) pacemaker cells indicated that shortened activity rhythms were derived from alterations in the molecular oscillator. Herein we present a mutation affecting clock function associated with a molecule involved in circuit assembly and maintenance.

None of the procedures described serves by itself to differentiate streptococci of human and bovine origin with certainty, though each of them serves as a strong presumptive test. Most strains fall easily into the human or bovine group by all the tests. Eliminating these from consideration we have left certain irregular strains listed in Table VII. See PDF for Structure Taking all characters into consideration we are inclined to regard Strains J-E7, Cheese 1, and Cheese 2 as undoubtedly of bovine origin. Strain J-MJ also is representative of a group of streptococci which Jones has found in milk and which is being further studied by him. There remains Strain J-C65 which for the present must be regarded as of doubtful origin.

Cytokine-induced killer (CIK) cell therapy has recently been used as an adjuvant setting following resection of hepatocellular carcinoma (HCC), while its benefit remains unclear. This study aimed to evaluate the efficacy of adjuvant CIK application in solitary HCC patients undergoing curative resection with stratification of microvascular invasion (MVI).In total, specimens and data from 307 solitary HCC patients undergoing curative resection between January 2007 and December 2010 were included. Of these, 102 patients received CIK treatment after surgery (CIK group), whereas 205 patients did not (control group). Pathological evaluation was used to retrospectively determine MVI status. The CIK group had 60 MVI-negative and 42 MVI-positive patients, while the numbers in control group were 124 and 81. Kaplan-Meier and Cox regression analyses were used to validate possible effects of CIK treatment on disease free survival (DFS) and overall survival (OS) as appropriate.For all patients, the CIK group exhibited significantly higher OS than the control group (log-rank test; PDFS = 0.055, POS = 0.020). Further analysis based on MVI stratification showed that for patients with MVI, DFS and OS did not differ between the 2 groups (PDFS = 0.439, POS = 0.374). For patients without MVI, the CIK group exhibited better DFS and OS than the control group (PDFS = 0.042, POS = 0.007), and multivariate analyses demonstrated that CIK treatment was an independent prognostic factor both for DFS and OS.For solitary HCC, CIK cell therapy after curative resection improves DFS and OS for patients without MVI, but has no statistically significant survival benefit for patients with MVI.

A few types of peptidergic clock neurons have been identified in the fruitfly Drosophila, whereas in blowflies, only pigment-dispersing factor (PDF)-immunoreactive lateral ventral clock neurons (LN(v)s) have been described. In blowflies, but not Drosophila, a subset of these PDF-expressing neurons supplies axon branches to a region outside the synaptic layer of the lamina, the most peripheral optic lobe neuropil. In Drosophila, similar lamina processes are instead supplied by non-clock neurons (LMIo) that express myoinhibitory peptide (MIP). We have investigated the distribution of MIP-immunoreactive neurons in the visual system of the blowfly Calliphora vomitoria and found neurons resembling the three LMIos, but without processes to the lamina. In Calliphora, PDF-immunoreactive processes of LN(v)s in the lamina closely impinge on branching serotonin-immunoreactive axon terminations in the same region. We have also identified, in the blowfly, two types of putative clock neurons that label with an antiserum to ion-transport peptide (ITP). The presence of serotonin-immunoreactive neurons supplying processes to the lamina seems to be a conserved feature in dipteran flies. The morphology of the two types of ITP-immunoreactive clock neurons might also be conserved. However, peptidergic neurons with branches converging on the serotonin-immunoreactive neurons in the lamina are of different morphological types and express PDF in blowflies and MIP in Drosophila. The central circuitry of these PDF- and MIP-expressing neurons probably differs; consequently, whether their convergence on serotonergic neurons subserves similar functions in the two species is unclear.

The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca²⁺ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca²⁺ baseline concentration and frequency of oscillating Ca²⁺ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca²⁺ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1-4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca²⁺ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K⁺ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K⁺ and Na⁺ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance.

Sleep disturbances are common in neurodegenerative diseases such as Alzheimer disease (AD). Unfortunately, how AD is mechanistically linked with interference of the body's natural sleep rhythms remains unclear. Our recent findings provide insight into this question by demonstrating that sleep disruption associated with AD is driven by epigenetic changes mediated by the histone acetyltransferase (HAT) Tip60. In this study, we show that Tip60 functionally interacts with the AD associated amyloid precursor protein (APP) to regulate axonal growth of Drosophila small ventrolateral neuronal (sLNv) pacemaker cells, and their production of neuropeptide pigment dispersing factor (PDF) that stabilizes appropriate sleep-wake patterns in the fly. Loss of Tip60 HAT activity under APP neurodegenerative conditions causes decreased PDF production, retraction of the sLNv synaptic arbor required for PDF release and disruption of sleep-wake cycles in these flies. Remarkably, excess Tip60 in conjunction with APP fully rescues these sleep-wake disturbances by inducing overelaboration of the sLNv synaptic terminals and increasing PDF levels, supporting a neuroprotective role for Tip60 in these processes. Our studies highlight the importance of epigenetic based mechanisms underlying sleep disturbances in neurodegenerative diseases like AD.

OBJECTIVE

To compare serum vitamin D levels and bone mineral density (BMD) values in patients with fibromyalgia and healthy controls.

BACKGROUND

The so far available reports of low levels of vitamin D and low BMD values in patients with fibromyalgia are inconsistent.

METHODS

Serum 25-hydroxyvitamin D (25-OHD) levels and BMD values were measured in thirty women with fibromyalgia and compared with thirty age-matched healthy women. Serum calcium, phosphorus, alkaline phosphatase and parathyroid hormone (PTH) levels were also measured. All participants completed the Fibromyalgia Impact Questionnaire (FIQ) and Hospital Anxiety and Depression Score (HADS). Pain severity was assessed with visual analog scale (VAS).

RESULTS

Mean serum 25-OHD levels did not differ between the groups (fibromyalgia 10.57 +/- 10.46, controls 10.87 +/- 5.52 ng/l; p=0.89); nor did the frequency of vitamin D deficiency (25-OHD < or = 20 ng/l) in each group (fibromyalgia 86.7%, controls 96.7%; p=0.353). Although, mean serum PTH level was found significantly higher in fibromyalgic patients than in controls (p=0.014), only one patient and two of controls had barely elevated PTH levels. There was no relationship between vitamin D level and FIQ score (p=0.707) or HADS (p=0.824) or pain VAS (p=0.414). BMD values in the patients with fibromyalgia were comparable to those in controls at both, the lumbar spine (p=0.866) and femur neck (p=0.61).

CONCLUSIONS

Neither vitamin D levels nor BMD values are different between women with and without fibromyalgia. In this cross-sectional study, mean serum PTH level was found higher in the fibromyalgic patients than in controls. Nevertheless, in order to confirm the findings of this preliminary study it is still necessary to perform a controlled longitudinal study (Tab. 2, Fig. 2, Ref. 35). Full Text in free PDF www.bmj.sk.

The above data relating to the reaction between 16 hour cultures of S. aureus and antistaphylococcus bacteriophage in nutrient broth of pH 7.6 at 36 degrees C. and with mechanical shaking to maintain a uniform B suspension, bring out the following points: (a) B growth in P-B mixtures does not differ from growth in controls without P except in the case of a very high initial P/B ratio as noted below. There is no evidence that lytic destruction of B begins shortly after mixing P and B nor that B growth is stimulated by P, for the B growth curves in the presence of ordinary [P]'s and in controls are identical. Only at the sudden onset of the rapid lytic process does the B curve of a P-B mixture deviate from the control curve. (b) B growth is an essential conditioning factor for P formation. (c) Both B growth and P production exhibit short lags. During this time P diffuses into or becomes adsorbed to B so rapidly that by the end of the lag period only 10 to 30 per cent of the total P present is extracellular, the remainder being associated with the B. (d) During the logarithmic B growth phase, P formation is also logarithmic but proceeds at a much faster rate. That is, d P/d t is proportional to a power of d B/d t. Consequently the statement that each time a B divides a certain amount of P is formed is not correct. (e) As B growth enters the phase of positive acceleration equilibrium between the extracellular and intracellular P fractions becomes established and is maintained up to the onset of lysis, extracellular [P] representing a small constant percentage of total [P]. The distribution of P on a constant percentage basis suggests the manner in which a relatively simple chemical compound would be distributed and is not at all typical of the distribution one would expect if P were a complex organized parasite. (f) When the value of log P/B = 2.1 lysis begins. Obviously, this limiting value for any initial [B] is reached sooner the higher the initial [P]. When log P/B at the time of mixing P and B is already 2.1 or greater, there is no growth of B and lysis soon occurs. (g) While there is good evidence that lysis is brought about by the attainment of a particular [P] per B and not by a certain [P] per ml., it is not clear at this time which of the ratios intracellular P/B, extracellular P/B or total P/B is the major conditioning factor for B lysis. (h) Experimentally the maximal [P]'s of lysates made by mixing a constant initial [B] with widely varying Po's fall within a relatively narrow range. This fact is explained by the large value of d log P/d t as compared to d log B/d t. That is, the loci of points at which log P = 2.1 + log B (maxima-lysis begins) on the curves of log P against t originating in various [Po]'s will lie at a nearly constant level above the abscissa. Because of this same relationship the maximal [P]'s of such a series will be in the reverse order of magnitude of the Po's, i.e., the larger the Po the smaller will be the maximal [P] attained during the reaction (cf. Fig, 16). (i) The lytic destruction of B is logarithmic with time, in this respect being similar to most death rate processes. The value -d log B/d t for a particular initial [B] is constant for various initial values of [P]. There is good evidence that cells need not be growing in order to undergo lysis. (j) During B lysis a considerable percentage of the total maximal P formed is destroyed, the chief loss probably occurring in the intracellular fraction. The major portion (70 to 90 per cent) of the final P present after the completion of bacteriophagy is set free during the brief phase of bacterial dissolution. (k) When the entire process of bacteriophagy is completed the lysates are left with certain [P]'s determined by the foregone P-B reaction. The destruction of P during lysis is sufficiently regular to maintain the relationship established at the maximal [P]'s. Therefore the final [P]'s have the same points in common that were noted in "h" as applying to the maximal [P]'s. That is, they all are grouped within a narrow range of [P] values, those having been made with high Po's being of lower titre than those made with low initial [P]'s. (1) There is a significant difference in the temperature coefficients of P and B formation. Further, the temperature coefficients of P and B destruction during lysis differ in almost the same ratio. Consequently, while all experimental evidence postulates B growth as an essential conditioning factor for P formation, the temperature coefficient data suggest that the two processes are basically separate reactions. A similar interpretation holds in the case of B dissolution and P inactivation. (m) The major events in the complete process of "bacteriophagy" are mathematically predictable. The [B] at which lysis occurs under certain standard conditions for given values of Bo and Po may be calculated from the equation: See PDF for Equation Substitution of this value for log B in the equation: See PDF for Equation gives satisfactory agreement with observed values for t((lysis)). (n) The kinetic analysis of the P-B reaction predicts that the values of log Po plotted against t((lysis)) for a constant Bo will give a straight line. This plot is employed in a method for the quantitative estimation of P described in an earlier paper on the basis of experimental observation alone. Its use is made more rational by the facts given above.

Isolated extramedullary relapse (IEMR) of acute leukemia (AL) after allogeneic bone marrow transplantation (BMT) is a rare occurrence. It is seen more commonly after BMT than after conventional chemotherapy (CHT) alone. We describe the natural history and response to treatment in four patients with IEMR following allogeneic BMT. The results indicate a stronger graft-versus-leukemia (GVL) effect in the marrow than in the peripheral tissues (Fig. 4, Ref. 13). Full Text (Free, PDF) www.bmj.sk.

OBJECTIVE

The aim of this clinical study was to assess virological response at end-of -treatment (ETR), sustained virological (SVR) and biochemical response in former drug users with chronic hepatitis C treated with PEG-IFN-alpha and R.

METHODS

Ninety two former drug users (21 F, 71 M) average age 27 years (18 to 41 years) and previously not treated with IFN-alpha and R (naive patients, pts) were evaluated for their virological and biochemical response. Standard treatment regimen of either 24 or 48 weeks was applied in patients with genotype 3 or genotype 1, respectively. SVR was considered if viral tests (HCV RNA) were negative 24 weeks after the end of treatment.

RESULTS

Overall SVR was attained in 87 (95%) of 92 treated patients, and therapy failed in 5 pts with genotype 1. In genotype 1 patients ETR and SVR were 81% and 86%, respectively (p < 0.001). In genotype 3 patients ETR and SVR were 98% and 100%, respectively (p < 0.001). ALT levels decreased significantly after 12 weeks of therapy (ALT 1.61 vs 0.64 micro/kat/l, p < 0.001) and were at normal levels during follow-up.

CONCLUSIONS

Crucial predictive factors resulting in high SVR were the younger age in combination with low stage of liver fibrosis, relatively short duration of viral infection, high proportion of genotype 3 and excellent adherence of patients to treatment regimen than previously not treated with IFN-alpha and R (naive patients). High proportion of SVR in former drug users has been achieved in patients with genotype 3 (100%) and genotype 1 (86%). The most decisive prognostic factor which favors high therapeutic efficacy appears to be young age and early onset of anti-HCV treatment (Tab. 3, Fig. 1, Ref. 33). Full Text (Free, PDF) www.bmj.sk.

BACKGROUND

Metabolic syndrome (MetS) represents a collection of markers associated with cardiovascular morbidity and mortality. Due to its high prevalence and steady increase of the occurrence, prevention or management of MetS is of paramount importance. The aim of our study was to evaluate MetS occurrence and extent of oxidative stress by comparing obese adults after diet optimization with untreated controls.

METHODS

Oxidative stress markers (total amount of free radicals, malondialdehyde, allantoin, alpha1-antiproteinase, GSSG/GSH ratio), total antioxidant capacity and lipid standardized alpha-tocopherol were determined in 40 obese people and 48 healthy controls. The obese people were divided into two group A: obese with restricted energy intake with lowered dietary carbohydrates (n=20) and group B: with the same grade of obesity but without following dietary recommendations (n=20).

RESULTS

Group A exhibited lower oxidative stress markers than group B; free radicals (5.18+/-1.68 vs 8.43+/-3.66 mmol/l, p<0.01), GSSG/GSH ratio (11.74+/-5.01 vs 15.38+/-5.93%, p<0.05) and higher antioxidants: lipid standardized alpha-tocopherol (3.70+/-0.51 vs 3.35+/-0.60, p<0.05) and ceruloplasmin (0.24+/-0.08 vs 0.21+/-0.03 g/l, p<0.05), in the course of same grade of obesity. Furthermore MetS occurrence was found significantly lower was in group A.

CONCLUSIONS

The energy intake restriction by 2000 kJ, mainly due to carbohydrate limitations, was associated with decreased oxidative stress and simultaneously increased lipid-standardized alpha-tocopherol and ceruloplasmin in obese people. These changes correlated with diminished MetS occurrence by about 50% (Tab. 3, Ref. 32). Full Text (Free, PDF) www.bmj.sk.

Plasma diafiltration (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside the hollow fibers. A prospective, multicenter study was undertaken to evaluate the changes in bilirubin, IL-18, and cystatin C, as well as the 28-day and 90-day survival rates, with the use of PDF according to the level of severity as measured by the Model for End-Stage Liver Disease (MELD) score. Twenty-one patients with liver failure were studied: 10 patients had fulminant hepatitis and PDF therapies were performed 28 times; 11 had acute liver failure with the therapy performed 96 times. Levels of total bilirubin, IL-18, and cystatin C decreased significantly after treatment. The 28-day survival rate was 70.0% and that at 90 days was 16.7%. According to the severity of the MELD score, each of the results compared well with the use of Molecular Adsorbent Recirculating System or Prometheus therapy. In conclusion, PDF appears to be one of the most useful blood purification therapies for use in cases of acute liver failure in terms of medical economics and the removal of water-soluble and albumin-bound toxins.

A patient with acute hepatic insufficiency induced by a drug presented to our institution, and we performed a novel plasmapheresis that we call plasma dia-filtration (PDF). The patient was a 36 year old woman. She underwent 11 sessions of PDF for a duration of about 9 h for each procedure using the Evacure EC-2A filter together with 20 units of fresh frozen plasma and dialysate simultaneously. Serum levels of total bilirubin and prothrombin time were significantly improved after she underwent each procedure. However, after the third procedure the levels returned to the same level as on the previous day. Encephalopathy improved after the first procedure, and this improvement was maintained until the ninth procedure. The patient prepared to undergo liver transplantation after the tenth procedure because of the development of hepatic coma, but she died of respiratory insufficiency before undergoing the procedure. Accordingly in this case, PDF worked to maintain liver function in acute liver failure and may act as bridge therapy until the patient can undergo liver transplantation.

The objective of this review is to introduce Merkel cells, to provide a basic overview on the theoretical background of function, development and clinical importance of Merkel cells. Merkel cells (MCs) are post-mitotic neuroendocrine cutaneous cells primarily localized in the epidermal basal layer of vertebrates and concentrated in touch-sensitive areas in glabrous, hairy skin and in some mucosa. There is a great site variation in the density of MCs. In routine light microscopy human MCs can hardly be identified. Cytokeratine 20 is a reliable marker with highest degree of specifity. MCs can be also distinguished by electron microscopy. The origin of human MCs has been controversial. Some investigators believe that it is a neural crest derivate, whereas others have proposed that it is a differentiation product of the fetal epidermal keratinocytes. Most studies focus on neuroendocrine functions and their possible malignant transformation into Merkel cell carcinomas (MCC). MCC is an uncommon and often aggressive malignancy and found mainly in elderly patients. It occurs most frequently in the head and neck region. MCC may be difficult to diagnose, it appears as a firm, painless lump. Diagnosis is based on typical histology representation on haematoxylin-eosin stained slides together with the results of immunohistochemistry. Histologically, MCC has been classified into three distinct subtypes: trabecular, intermediate and small cell type. Radical surgery is the recomended procedure for the treatment of primary MCC. Oncological treatment is generally reserved for stage III. (distant metastases) cases of MCC (Tab. 1, Fig. 13, Ref. 58). Full Text in free PDF www.bmj.sk.

We investigated the binding of a naturally occurring antibiotic, actinonin, to the Ni(2+)-reconstituted recombinant form of Escherichia coli peptide deformylase (PDF(Ec)) via isothermal titration microcalorimetry. The binding data conformed to both exothermic and endothermic phases with magnitudes of DeltaG degrees , DeltaH degrees , and TDeltaS degrees being equal to -12, -2.7, and 9.3 kcal/mol and -8.7, 3.9, and 12.6 kcal/mol, respectively. Evidently, although both phases are dominated by favorable entropic changes, the exothermic phase has about 6.7 kcal/mol enthalpic advantage over the endothermic phase. We observed that the removal of bound Ni(2+) from PDF(Ec) abolished the exothermic phase without affecting the endothermic phase, but it was regained upon addition of Zn(2+). In conjunction with metal analysis data, we propose that the recombinant form of PDF(Ec) is expressed in two stable conformational states that yield markedly distinct ITC profiles (i.e., exothermic versus endothermic) upon interaction with actinonin. The existence of two conformational states of PDF(Ec) is further supported by the observation of two distinct and independent transitions during the thermal unfolding of the enzyme. In addition, the thermodynamic data reveal that the formation of the PDF(Ec)-actinonin complex results in the transfer of one H(+) from the enzyme phase to the bulk solvent at pH 6.3. Both exothermic and endothermic phases produce highly negative DeltaC(p) degrees values, but there is no apparent enthalpy-entropy compensation effect upon formation of the PDF(Ec)-actinonin complex. In view of the known structural features of the enzyme, arguments are presented that the alternative conformational states of PDF(Ec) are modulated by the metal ligation at the enzyme site.

A series of isoxazole-3-hydroxamic acid derivatives has been identified as a new class of small, nonpeptidic inhibitors of peptide deformylase (PDF). The synthesis, enzyme inhibition and preliminary investigation of the binding mode of this potential antibacterial compounds are reported.

OBJECTIVE

To compare the in vitro activity of NVP-LMB415 (formerly referred to as NVP-PDF 713) with that of other agents with anti-anaerobe activity against clinical anaerobic isolates, with emphasis on the Bacteroides fragilis group.

METHODS

The MICs for 405 B. fragilis group and 102 Gram-positive anaerobic isolates were determined using NCCLS-recommended procedures. The activity of NVP-LMB415 was compared with that of cefoxitin, clindamycin, imipenem, garenoxacin, linezolid, moxifloxacin and tigecycline. Vancomycin was included in the evaluation of the Gram-positive organisms.

RESULTS

NVP-LMB415 showed excellent in vitro activity against all the species of the B. fragilis group isolates (MIC range < or = 0.03-0.5 mg/L and MIC(90) 0.5 mg/L). NVP-LMB415 was active against B. fragilis group strains resistant to beta-lactams, quinolones or clindamycin, and the MICs were much lower than those of newer agents such as linezolid, tigecycline and garenoxacin. The MICs of NVP-LMB415 (>> or = 4 mg/L) for Clostridium species were higher than the MICs for other anaerobes.

CONCLUSIONS

Given the frequency of isolation of anaerobic bacteria and their increasing resistance to all classes of antibiotics, NVP-LMB415 is an ideal agent for potential use against mixed infections caused by resistant anaerobic pathogens such as of B. fragilis and Gram-positive aerobic strains such as methicillin-resistant staphylococci, streptococci and enterococci.

Peptide deformylases (PDFs) constitute a growing family of hydrolytic enzymes previously believed to be unique to Eubacteria. Recent data from our laboratory have demonstrated that PDF orthologues are present in many eukaryotes, including several parasites. In this report we aim to explain why PDF could be considered to be a potent target for human and veterinary antiparasitic treatments.

This work investigates the possibilities of applying high-angular-resolution-diffusion-imaging- (HARDI-) based methods in a clinical setting by investigating the performance of non-Gaussian diffusion probability density function (PDF) estimation for a range of b-values and diffusion gradient direction tables. It does so at realistic SNR levels achievable in limited time on a high-performance 3T system for the whole human brain in vivo. We use both computational simulations and in vivo brain scans to quantify the angular resolution of two selected reconstruction methods: Q-ball imaging and the diffusion orientation transform. We propose a new analytical solution to the ODF derived from the DOT. Both techniques are analytical decomposition approaches that require identical acquisition and modest postprocessing times and, given the proposed modifications of the DOT, can be analyzed in a similar fashion. We find that an optimal HARDI protocol given a stringent time constraint (<10 min) combines a moderate b-value (around 2000 s/mm(2)) with a relatively low number of acquired directions (>48). Our findings generalize to other methods and additional improvements in MR acquisition techniques.

We describe labeling of neurons in the central nervous system of two cricket species, Teleogryllus commodus and T. oceanicus, with both mono- and polyclonal antibodies against the PER protein. Western blots reveal that the monoclonal antibodies recognize a single protein with a molecular weight of approximately 94 kDa, i.e., similar to that of the PER protein of the moth, Anterea pernii. Neurons and their processes are labeled both in the optic lobes and in the central brain. Processes occur in the accessory medulla, the medulla, and proximal lamina, in the central complex, in the non-glomerular neuropil, and in the retrocerebral complex, suggesting that PER-containing neurons form a widely distributed network. Neurons and processes were also labeled in the meso- and metathoracic ganglia. Four to six PER-immunoreactive (ir) neurons with processes in the accessory medulla were double labeled by an antibody against pigment-dispersion factor (PDF), a peptide that is implicated in circadian rhythmicity in Drosophila. In the central brain, projections of fibers labeled by the anti-PER and anti-PDF antibodies were mainly distinct, with overlap only in a few restricted regions. In most neurons, including those projecting into the accessory medulla, PER labeling was restricted to the cytoplasm and there was no indication of circadian variation in the intensity of staining.

BACKGROUND

Notable experience using the vacuum assisted closure for abdominal wall defects was an assumption for its intra-abdominal application in severely septic patients with intra-abdominal infection. The goal of this study was to evaluate our experience with this new therapeutic technique.

METHODS

This study is a retrospective analysis and comparison of two groups of patients with severe sepsis and proven intra-abdominal source of infection. Group A consisted of 41 patients, 31 men and 10 women with the age ranging 18-78 years old (mean 49.5), who were treated surgically between 1998 and 2002 using a combination of laparostomy, multiple irrigations and abdominal drainage. Group B consisted of 46 patients, 32 men and 14 women age 18-87 years old (mean 50.8), who were treated between 2002 and 2006 using former techniques with the addition of an intra-abdominal vacuum assisted negative pressure therapy system.

RESULTS

In the group A the number of re-laparotomies with debridement of the open abdominal wound in general anesthesia ranged from 5 to 18 over 10 to 35 days (mean 19.4) of hospital stay. In the group B, the number of re-laparotomies decreased to 3-9 and the hospital stay decreased to 7-29 days (mean 14.5). Fifteen patients (36.6%) in the group A died because of severe sepsis, compared to 11 patients (23.9%) in the group B.

CONCLUSIONS

Authors confirmed a significant reduction of morbidity and mortality using the intraabdominal vacuum assisted system in the treatment of localized intra-abdominal sepsis (Tab. 2, Ref 18). Full Text (Free, PDF) www.bmj.sk.