Inhibition of MMP-9 by a selective gelatinase inhibitor protects neurovasculature from embolic focal cerebral ischemia

ABSTRACT: BACKGROUND: Cerebral ischemia has been shown to induce activation of matrix metalloproteinases (MMPs), particularly MMP-9, which is associated with impairment of the neurovasculature, resulting in blood-brain barrier breakdown, hemorrhage and neurodegeneration. We previously reported that the thiirane inhibitor SB-3CT, which is selective for gelatinases (MMP-2 and 9), could antagonize neuronal apoptosis after transient focal cerebral ischemia. RESULTS: Here, we used a fibrin-rich clot to occlude the middle cerebral artery (MCA) and assessed the effects of SB-3CT on the neurovasculature. Results show that neurobehavioral deficits and infarct volumes induced by embolic ischemia are comparable to those induced by the filament-occluded transient MCA model. Confocal microscopy indicated embolus-blocked brain microvasculature and neuronal cell death. Post-ischemic SB-3CT treatment attenuated infarct volume, ameliorated neurobehavioral outcomes, and antagonized the increases in levels of proform and activated MMP-9. Embolic ischemia caused degradation of the neurovascular matrix component laminin and tight-junction protein ZO-1, contraction of pericytes, and loss of lectin-positive brain microvessels. Despite the presence of the embolus, SB-3CT mitigated these outcomes and reduced hemorrhagic volumes. Interestingly, SB-3CT treatment for seven days protected against neuronal laminin degradation and protected neurons from ischemic cell death. CONCLUSION: These results demonstrate considerable promise for the thiirane class of selective gelatinase inhibitors as potential therapeutic agents in stroke therapy.     

Electrophysiological Characteristics of Globus Pallidus Neurons

Extracellular recordings in primates have identified two types of neurons in the external segment of the globus pallidus (GPe): high frequency pausers (HFP) and low frequency bursters (LFB). The aim of the current study was to test whether the properties of HFP and LFB neurons recorded extracellularly in the primate GPe are linked to cellular mechanisms underlying the generation of action potential (AP) firing. Thus, we recorded from primate and rat globus pallidus neurons. Extracellular recordings in primates revealed that in addition to differences in firing patterns the APs of neurons in these two groups have different widths (AP_ex). To quantitatively investigate this difference and to explore the heterogeneity of pallidal neurons we carried out cell-attached and whole-cell recordings from acute slices of the rat globus pallidus (GP, the rodent homolog of the primate GPe), examining both spontaneous and evoked activity. Several parameters related to the extracellular activity were extracted in order to subdivide the population of recorded GP neurons into groups. Statistical analysis showed that the GP neurons in the rodents may be differentiated along six cellular parameters into three subgroups. Combining two of these groups allowed a better separation of the population along nine parameters. Four of these parameters (F_max, AP_amp, AP_hw, and AHP_s amplitude) form a subset, suggesting that one group of neurons may generate APs at significantly higher frequencies than the other group. This may suggest that the differences between the HFP and LFB neurons in the primate are related to fundamental underlying differences in their cellular properties.     

Low efficacy rate of moxifloxacin-containing Helicobacter pylori eradication treatment: in an observational study in a Turkish population

BACKGROUND: Standard triple therapy for Helicobacter pylori has an eradication rate of about 50% in Turkey. It may be due to an increased resistance of H. pylori to antibiotics. Therefore, we aimed to investigate the effectiveness of a new second-generation fluoroquinolone, moxifloxacin-containing triple therapy in H. pylori eradication. MATERIAL AND METHODS: This is an open-label, prospective, single-center, pilot study. We studied 71 dyspeptic patients infected with H. pylori diagnosed by both histology and rapid urease test. Out of 71 dyspeptic patients, 64 had non-ulcer dyspepsia and seven had peptic ulcer. Patients received pantoprazole (40 mg b.i.d.) plus moxifloxacin (400 mg/day) and amoxicillin (1000 mg b.i.d.) for 14 days. Eradication was assessed 4 weeks after completing the therapy by histology and rapid urease test. Per-protocol and intention-to-treat eradication rates were determined. RESULTS: The eradication rate was 42.2% for the intention-to-treat analysis and 47.6% for the per-protocol analysis. Of all patients included in the study, 29.5% had side-effects and only 2.8% of the patients discontinued the treatment because of side-effects. Most of the complications were mild and self-limiting. CONCLUSION: Triple therapy with pantoprazole, moxifloxacin, and amoxicillin for 14 days yielded unacceptably low eradication rates. However, using tests of susceptibility to antibiotics, further studies with larger sample sizes are needed to judge these eradication rates of moxifloxacin containing eradication treatment.     

Dispersed activity during passive movement in the globus pallidus of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primate

Parkinson's disease is a neurodegenerative disorder manifesting in debilitating motor symptoms. This disorder is characterized by abnormal activity throughout the cortico-basal ganglia loop at both the single neuron and network levels. Previous neurophysiological studies have suggested that the encoding of movement in the parkinsonian state involves correlated activity and synchronized firing patterns. In this study, we used multi-electrode recordings to directly explore the activity of neurons from the globus pallidus of parkinsonian primates during passive limb movements and to determine the extent to which they interact and synchronize. The vast majority (80/103) of the recorded pallidal neurons responded to periodic flexion-extension movements of the elbow. The response pattern was sinusoidal-like and the timing of the peak response of the neurons was uniformly distributed around the movement cycle. The interaction between the neuronal activities was analyzed for 123 simultaneously recorded pairs of neurons. Movement-based signal correlation values were diverse and their mean was not significantly different from zero, demonstrating that the neurons were not activated synchronously in response to movement. Additionally, the difference in the peak responses phase of pairs of neurons was uniformly distributed, showing their independent firing relative to the movement cycle. Our results indicate that despite the widely distributed activity in the globus pallidus of the parkinsonian primate, movement encoding is dispersed and independent rather than correlated and synchronized, thus contradicting current views that posit synchronous activation during Parkinson's disease.     

Temporoparietal fascia: an anatomic and histologic reinvestigation with new potential clinical applications

Temporoparietal fascia constitutes a very important structural unit from both an aesthetic and a reconstructive surgical point of view. A histologically supported anatomic study was conducted for the reappraisal of the anatomic relationships and clinical application potentials of the data obtained. Anatomy of the temporoparietal fascia was investigated on 20 sides from 10 cadavers. After dissections, necropsies were obtained to demonstrate histologic features of the temporoparietal fascia. The outer part of the temporoparietal fascia is continuous with the superficial musculoaponeurotic system (SMAS) in the inferior border and with orbicularis oculi and frontalis muscles in the anterior border. Therefore, plication of the temporoparietal fascia can increase tightness of the SMAS, orbicularis oculi, and frontalis muscle in rhytidectomy. The frontal branches of facial nerve were noted to course parallel to the frontal branch of the superficial temporal artery, lying deeper to the temporoparietal fascia within the innominate fascia. In the view of these findings, conventional subfascial dissection, which is performed to protect frontal branches of the facial nerve, is not reasonable during the temporal part of rhytidectomy. Careful subcutaneous dissection just under the hair follicles is more appropriate to avoid nerve injury and also provides excellent exposure of the temporoparietal fascia for plication in rhytidectomy with protection of the auriculotemporal nerve and the superficial temporal vessels. Furthermore, two layered structures of the temporoparietal fascia are very suitable to insert a framework into the temporoparietal fascia for ear reconstruction to eliminate some of the shortcomings of Brent's technique. A thin muscle layer was also noted within the outer part of the temporoparietal fascia below the temporal line; the term "temporoparietal myofascial flap" would, therefore, be more accurate than "temporoparietal fascial flap." Finally, the innominate fascia and the deep temporal fascia can be elevated with the two layers of the temporoparietal myofascial flap to obtain a well-vascularized, four-layered myofascial flap based on the superficial temporal vessels. This multilayered flap can be used to reconstruct all defects when fine, pliable, thin, multilayered flaps are required.     

Effect of physiological state of young Ceratitis capitata females, on resource foraging behavior

We investigated the influence of the physiological state of young female Ceratitis capitata (Diptera: Tephritidae) on resource foraging behavior and mating propensity in field cage studies. Three kinds of diets were supplied prior to release on host plants: (1) 2% sucrose, (2) 20% sucrose, and (3) protein hydrolysate. Laboratory-cultured C. capitata females of different ages, ranging between 3–9 days old, were released in field cages containing two potted citrus tree seedlings, each consisting of either proteinacous or carbohydrate sources. Flies 3–7 days old, exposed to 2% sucrose, showed no preference for either source, while other groups, at the same age, displayed a significant influence of diet. Conversely, the behavior of flies within the age 8–9 days old was governed only by their reproductive needs, all three groups being significantly attracted to protein. In additional field-cage studies, mating propensity of similar groups was observed. Copulation was significantly higher among immature flies fed on proteinacous diet than those exposed to carbohydrate sources prior to their release.