Mucosal vs. cutaneous advancement flaps for the treatment of chronic anal fissures: a randomized clinical trial.

PURPOSE: The aim of this study was to compare two surgical treatment methods for chronic anal fissures (CAF), mucosal advancement flap anoplasty (MAFA) and cutaneous advancement flap anoplasty (CAFA). METHODS: A randomized, blinded clinical trial was conducted on patients with CAF refractory to medical treatment referred to a tertiary-level hospital between January 2021 and December 2022. The patients were assigned to two groups by block randomization and were compared in terms of outcome, pain reduction, and complications. RESULTS: There were 30 patients (male to female ratio 2:3, median age 42 years [range 25-59 years]). Both techniques reduced anal pain significantly (p = 0.001); however, there were no significant differences between MAFA and CAFA groups in recurrence, duration of healing, postoperative pain, and postoperative bleeding. No patient suffered from fecal incontinence (Wexner score = 0) or flap necrosis postoperatively. Only two patients in the MAFA group (1 and 3 months after surgery) and one patient in the CAFA group (2 months after surgery) had recurrence (total recurrence rate = 10%, healing rate = 90%). All of the patients were satisfied with their surgical results. CONCLUSION: Mucosal and cutaneous anal advancement flap techniques are effective and comparable surgical procedures for the treatment of chronic anal fissures with minimal complications, fast healing process, and minimal postoperative pain and complications. CLINICAL TRIAL ID: IRCT20120129008861N4 ( www.irct.ir ).

Efficiency of an infiltration basin in removing contaminants from urban stormwater.

The efficiency of a Stormwater Infiltration Basin (SIB) to remove contaminants from urban stormwater was assessed in the current investigation. The SIB, installed in an urban suburb in eastern Sydney (Australia), was monitored over seven rainfall events to assess the removal efficiency of the remedial device for total suspended solids (TSS), nutrients (TP, TKN, N(ox), TN), trace metals (Cd, Cr, Cu, Fe, Mn, Ni, Pb, Zn), organochlorine pesticides and faecal coliforms (FC) from stormwater. The weighted average concentration (WAC) of TSS in the stormwater effluent from the SIB was reduced by an average of 50%, whereas the WAC of Cu, Pb and Zn were also reduced by an average 68%, 93% and 52%, respectively. However, the WAC of Cr, Fe, Mn and Ni displays either similar concentrations as the stormwater influent (Cr and Mn), or substantially higher concentrations (Fe and Ni), due possibly to leaching of fine-grained zeolite clay particles in the filtration bed. The mean removal efficiency of the SIB for total phosphorus (TP) and total Kjeldahl nitrogen (TKN) was 51% and 65%, respectively. In contrast, the average WAC of oxidisable nitrogen (nitrate and nitrite nitrogen or N(ox) is about 2.5 times greater in the effluent (1.34 +/- 0.69 mg L(-1)) than in the incoming stormwater (0.62 +/- 0.25 mg L(-1)). The WAC of total nitrogen (TN) was similar for stormwater at the in-flow and out-flow points. The SIB was very efficient in removing FC from stormwater; and the WAC of almost 70000 cfu (100 mL)(-1) at inflow was reduced to <2000 cfu (100 Ml)(-1) at the outflow, representing a mean removal efficiency of 96%. Due to the low concentrations of Cd, organochlorine pesticides and PAHs in the stormwater, it was not possible to assess the efficiency of the SIB in removing these contaminants.

Elucidation of the molecular actions of NCAM and structurally related cell adhesion molecules.

The Neural Cell Adhesion Molecule (NCAM) is a founder member of a large family of cell surface glycoproteins that share structural motifs related to immunoglobulin and fibronectin type III (FN III) domains [Walsh and Doherty (1991) (Fig. 1). These glycoproteins have been grouped based on the respective number of each type of domain. In vertebrates members of this family of glycoproteins include L1/NILE, NgCAM, axonin-1/TAG-1, and Thy-1 as well as NCAM. In addition structural homologs of NCAM and L1 have been identified in Drosophila and Grasshoppers [Walsh and Doherty (1991)]. These insect homologs are called fasciclins and a series of mutants corresponding to these aspects of synaptic plasticity [Mayford et al. (1992) Science 256:638-644]. In vertebrates all of these glycoproteins are expressed in the developing nervous system where they have been identified as candidate molecules for mediating axon outgrowth, fasciculation, regeneration, and target recognition. In addition, NCAM is expressed in a number of different tissues and cell types. For example, NCAM is expressed in a dynamic pattern in developing and regenerating adult muscle. In this review we aim to describe important aspects of the role of these CAMS in development of the nervous system, including the neuromuscular junction. Furthermore, we will explore the prospective use of molecular biology, cell biology, and molecular genetic techniques, such as transgenic mice, to understand the role and molecular action of this family of cell adhesion molecules in vivo.

The neural cell adhesion molecule and synaptic plasticity.

Highly stereotyped patterns of neuronal connections are laid down during the development of the nervous system via a range of activity independent and activity dependent mechanisms. Whereas the coarse hard-wiring of the nervous system appears to rely on molecular recognition events between the neuron, its pathway, and its target, the establishment of precisely patterned functional circuits is thought to be driven by neuronal activity. In this review we discuss the role that the neuronal cell adhesion molecule (NCAM) plays in morphological plasticity. Recent studies on NCAM and its probable species homologue in Aplysia (apCAM) suggests that an individual CAM can function to both promote synaptic plasticity and maintain the structure of the synapse. In the adult brain, changes between stability and plasticity are likely to underlie dynamic morphological changes in synaptic structures associated with learning and memory. In this review we use NCAM as an example to illustrate mechanisms that can change the function of an individual CAM from a molecule that promotes plasticity to one that does not. We also discuss evidence that NCAM promotes plasticity by activating a conventional signal transduction cascade, rather than by modulating adhesion per se. Finally, we consider the evidence that supports a role for NCAM in learning and memory.

Increase in extracellular NCAM and amyloid precursor protein following induction of long-term potentiation in the dentate gyrus of anaesthetized rats.

The extracellular concentrations of the amyloid precursor protein (APP) and neural-cell adhesion molecule (NCAM) in the dentate gyrus of the anaesthetized rat were assayed before and after the induction of long-term potentiation (LTP) in vivo. Levels of high molecular weight neurofilament protein and activity of the lysosomal enzyme arylsulphatase were measured as internal controls and indicators of neuronal damage. Ninety minutes after the induction of LTP, the concentrations of NCAM and APP increased, in an NMDA-dependent manner, in the absence of changes in neurofilament and arylsulphatase levels. The delayed changes in the extracellular concentration of these molecules may reflect events leading to morphological modifications following LTP.

Changes in protein synthesis accompanying long-term potentiation in the dentate gyrus in vivo.

The possibility that the induction of long-term potentiation (LTP) is followed by changes in protein synthesis has been examined using high-resolution two-dimensional gel electrophoresis. 35S-methionine, infused into the third ventricle of anesthetized rats, was used to label hippocampal proteins. LTP was induced unilaterally in the dentate gyrus by tetanic stimulation of the perforant path, and followed either for 1 hr or for 3 hr. Two-dimensional gel autoradiographs were quantitatively analyzed using the PDQUEST system (Protein Databases Inc.). One hour after the unilateral induction of LTP, only one protein spot was found to be statistically different in intensity from corresponding spots in the contralateral control side. Three hours after LTP, however, 11 spots were found to have altered densities. Examination of basic proteins using the nonequilibrium pH gel electrophoresis system revealed changes in three proteins in the 3 hr group. Reductions as well as increases in spot intensities were observed. The results indicate that LTP is associated with a complex pattern of changes in protein synthesis.

Pertussis toxin treatment increases glutamate release and dihydropyridine binding sites in cultured rat cerebellar granule neurons.

This study was designed to examine the ability of pertussis toxin to block various responses due to (-)-baclofen in cultured cerebellar granule neurons of the rat. Treatment with pertussis toxin for 3 h markedly reduced the ability of (-)-baclofen to stimulate GTPase in membranes, and its ability to inhibit forskolin-stimulated adenylyl cyclase in intact cells, whereas the ability of (-)-baclofen to inhibit glutamate release was not affected at 3 h, but was abolished after 16 and 48 h treatment with pertussis toxin. The amount of ADP-ribosylation of Gi/Go due to pertussis toxin in intact cells correlated well with the former two effects, but not with the prevention of the ability of baclofen to inhibit glutamate release. Pertussis toxin treatment for up to 48 h did not significantly affect the levels of Gs, Gi and Go in membranes from granule neurons determined by immunoblotting. Pertussis toxin treatment for 16 or 48 h but not 3 h increased the total amount of stimulated release of glutamate by about 40% under normal conditions, and by 84% under depolarizing conditions. In parallel experiments it was observed that pertussis toxin treatment for 16 h increased the number of dihydropyridine binding sites by about 90% on intact granule neurons. Whole-cell calcium channel currents, recorded under several conditions in the cells, were not increased in amplitude by pertussis toxin treatment for up to 48 h, although the ability of baclofen to inhibit calcium channel currents was blocked by pertussis toxin. These results indicate that the pertussis toxin-induced increase in glutamate release may be due to an increase in dihydropyridine binding sites, possibly localized to the presynaptic terminals.

Increased efflux of a haemoglobin-like protein and an 80 kDa protease into push-pull perfusates following the induction of long-term potentiation in the dentate gyrus.

In a previous communication, we reported an increase in protein efflux into perfusates obtained from push-pull cannulation of the dentate gyrus, following induction of long-term potentiation (LTP) in the perforant path. LTP was accompanied by a delayed but general increase in protein efflux. Protein B5 (MW 14 kDa), because of its relatively high concentration in the perfusates and absence from serum, has been chosen for further characterization. Spectrophotometric analysis, in situ proteolysis, two-dimensional electrophoresis and immunoblotting, revealed that protein B5 is indistinguishable from haemoglobin. A persistent increase in an 80 kDa protease, detected by SDS-PAGE zymography, was also seen after the induction of LTP. We consider the possibility that the increased haemoglobin content of perfusates after the induction of LTP may reflect an LTP-associated increase in the release (or activation) of proteases into extracellular space, leading to proteolytic breakdown of blood clots in the vicinity of the cannula. Evidence in favour of this hypothesis is provided.

Long-term potentiation in the dentate gyrus of the anaesthetized rat is accompanied by an increase in protein efflux into push-pull cannula perfusates.

Changes in protein content of push-pull cannula perfusates from the dentate gyrus of anaesthetized rats were analyzed before and after the induction of long-term potentiation (LTP). LTP, induced by either high-frequency stimulation of the perforant path or raising the extracellular calcium concentration, was associated with increases in the protein content of the perfusates. Tetanically induced LTP was accompanied with a large but delayed increase (apparent in the second hour after the stimulation) in protein efflux. In contrast, when LTP was induced by the elevation of extracellular calcium concentration, a smaller but more immediate increase in protein efflux was observed. When 5-D-aminophosphonovalerate was used to block the induction of LTP, no increase was observed in either case. These results indicate that LTP in the dentate gyrus is accompanied by an increase in the efflux of proteins into push-pull cannula perfusates. The possible origins of these proteins and their role in LTP are discussed.