Retinal thickness study with optical coherence tomography in patients with diabetes

PURPOSE: To quantitatively assess retinal thickness by optical coherence tomography (OCT) in normal subjects and patients with diabetes. This study was intended to determine which retinal thickness value measured with OCT best discriminates between diabetic eyes, with and without macular edema. METHODS: OCT retinal thickness was measured by a manual technique in a total of 26 healthy volunteers (44 control eyes) and 85 patients with diabetes (148 eyes) with the clinical diagnosis of no diabetic retinopathy (45 eyes), nonproliferative diabetic retinopathy without clinically significant macular edema (CSME; 54 eyes), proliferative diabetic retinopathy without CSME (21 eyes), and 28 eyes with diabetic retinopathy with CSME. Independent predictors of the presence of CSME were quantified by using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were generated to evaluate and compare the predictor variables. The correlation of retinal thickness measurements and visual acuity was calculated. RESULTS: There were statistically significant differences in foveal thickness between control eyes and all the other eye groups (P = 0.001). Diabetic eyes with CSME had a statistically significant greater thickness in each of the areas compared with the other groups. In a multivariate logistic regression model, foveal thickness was a strong and independent predictor of CSME (odds ratio [OR], 1.037; 95% confidence interval [CI] 1.02-1.05). The area under the ROC curve of this predictor variable was 0.94 (P = 0.001). For a cutoff point of 180 microm, the sensitivity was 93%, and specificity was 75%. Foveal thickness correlated with visual acuity in a log minimum angle of resolution (logMAR) scale (Spearman's rho = 0.9, P = 0.001). CONCLUSIONS: These results suggest that foveal thickening over 180 microm measured by OCT may be useful for the early detection of macular thickening and may be an indicator for a closer follow-up of the patient with diabetes.     

Occupational health in Central America

The 12.4 million economically active population (EAP) of the seven Central American countries includes a large informal sector. Social security covers only 14-60%. No surveillance of occupational safety and health (OSH) hazards or accidents exists. Extrapolating the incidence of occupational accidents among insured Costa Rican workers to the Central American EAP yields two million accidents yearly, still a gross underestimate. Occupational diseases are underreported, misdiagnosed, and not recognized as such. A number of regional OSH programs aim at modernization of the labor administrations and address the formal sector, in particular textile maquila, in connection with free trade agreements. The weak role of the ministries of health is expected to strengthen under the Pan American Health Organization OSH program. Employers largely influence new policies. Workers' influence on OSH policies has been weak, with only about 10% unionization rate and scarce resources and OSH knowledge. Informal workers, however, are getting organized. OSH research is underdeveloped and not linked to policy making. Construction, agriculture, and general un/underemployment are considered priorities for intervention. The informal sector needs to be included in national and regional OSH policies. Regional collaboration and international development support are of strategic importance to achieve sustainable improvement in OSH.     

PARP cleavage, DNA fragmentation, and pyknosis during excitotoxin-induced neuronal death

Poly(ADP-ribose)polymerase-1 (PARP-1) is a nuclear enzyme activated by DNA breaks and serves a role in DNA repair through the formation of polymers (poly(ADP)ribosylation) at sites of DNA damage. PARP-1 is activated by DNA damage in neurons of the hippocampus and cerebral cortex following excessive exposure to glutamate receptor agonists such as NMDA or kainic acid. In addition, recent studies suggest that degradation of PARP-1 occurs in cells that undergo apoptotic versus nonapoptotic forms of cell death. To investigate this process further, we examined the spatiotemporal aspects of excitotoxic injury in the rodent visual cortex by making focal intracerebral injections of kainic acid. These injections resulted in DNA damage, PARP-1 activation, and neuronal cell death over a 5-day period. Rapid neuronal cell injury assessed by Fluoro-Jade staining appeared within hours, but increased TUNEL staining occurred only after 24 h. A dramatic increase in caspase-3 activity, as well as an increase in the number of neurons containing active caspase-3, peaked 2 days after injury. Last, increased PARP-1 immunoreactivity and PARP-1 cleavage reached peak levels 2 to 3 days after delivering the excitotoxin. These findings suggest that increased caspase-3 activity may regulate the degradation of PARP-1 in subsets of cortical neurons during excitotoxic cell death.     

Immunohistochemical study of distribution of apolipoproteins E and D in human cerebral beta amyloid deposits

Several molecules are known to be closely associated with amyloid deposits in human brain. Among these, apolipoproteins such as apolipoproteins E (apo E) and J (apo J) have been found in two neuropathological hallmarks of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA): senile plaques (SPs) and cerebrovascular amyloid. These apolipoproteins may be implicated in amyloid fibrillogenesis. Apo D is a multiligand-multifunctional glycoprotein present in SPs, as we previously reported. The aim of this work is to study the link between immunolocalization of apo E and apo D in AD and CAA brains. Both apolipoproteins were found in all types of SPs, but apo E was observed more often than apo D in mature plaques. Whereas apo E is always located overlapping the amyloid core, apo D seems to situate preferably around and near the amyloid. Immunohistochemistry revealed that these apolipoproteins behave differently in cerebral vessels. Apo E labeling in vessels appears mainly linked to amyloid deposits, whereas apo D shows a distribution almost opposite to that of apo E. This could be an indication of the different roles that each apolipoprotein plays in the pathogenesis of amyloid deposition.     

Expression of the genes GAD67 and Distal-less-4 in the forebrain of Xenopus laevis confirms a common pattern in tetrapods

We investigated whether gamma-amino butyric acidergic (GABAergic) cell populations correlate positionally with specific Dlx-expressing histogenetic territories in an anamniote tetrapod, the frog Xenopus laevis. To that end, we cloned a fragment of Xenopus GAD67 gene (xGAD67, expressed in GABAergic neurons) and compared its expression with that of Distal-less-4 gene (xDll-4, ortholog of mouse Dlx2) in the forebrain at late larval and adult stages. In Xenopus, GABAergic neurons were densely concentrated in xDll-4-positive territories, such as the telencephalic subpallium, part of the hypothalamus, and ventral thalamus, where nearly all neurons expressed both genes. In contrast, the pallium of Xenopus generally contained dispersed neurons expressing xGAD67 or xDll-4, which may represent local circuit neurons. As in amniotes, these pallial interneurons may have been produced in the subpallium and migrated tangentially into the pallium during development. In Xenopus, the ventral division of the classic lateral pallium contained extremely few GABAergic cells and showed only low signal of the pallial gene Emx1, suggesting that it may represent the amphibian ventral pallium, homologous to that of amniotes. At caudal forebrain levels, a number of GABAergic neurons was observed in several areas (dorsal thalamus, pretectum), but no correlation to xDll-4 was observed there. The location of GABAergic neurons in the forebrain and their relation to the developmental regulatory genes Dll and Dlx were very similar in Xenopus and in amniotes. The close correlation in the expression of both genes in rostral forebrain regions supported the notion that Dll/Dlx are among the genes involved in the acquisition of the GABAergic phenotype.     

Functional MRI-BOLD of brainstem structures during visually triggered migraine

BACKGROUND: Previously, hyperoxia and blood volume increase were reported in the red nucleus and substantia nigra during spontaneous migraine with aura. OBJECTIVE: To further understand the pathophysiologic role of these centers, activation of brainstem structures was investigated in patients with visually triggered migraine. METHODS: Twenty-six patients with migraine (23 with aura and 3 without aura), and 10 normal control subjects were studied with blood oxygen level-dependent (BOLD) fMRI during repeated checkerboard visual stimulation. Three axial image sections, which covered the occipital cortex and brainstem, were acquired 224 times with a temporal resolution of 3.5 seconds. RESULTS: Repetitive visual stimulation triggered symptoms in 12 patients; four who had migraine with aura developed both visual symptoms and headaches, and six who had migraine with aura and two who had migraine without aura had headaches only. Four patients who had migraine with aura experienced the onset of their usual aura or onset of their typical headache either during the experiment or immediately after. In the remaining 10 patients with migraine, and all control subjects, visual stimulation failed to trigger symptoms at any time. In 75% of the patients who developed symptoms during stimulation, baseline T2*-weighted MR signal intensities increased in the red nucleus and substantia nigra before occipital cortex signal elevation or the onset of visually triggered symptoms. CONCLUSION: Activation (hyperoxia and blood volume increase) of the red nucleus and substantia nigra in association with visually triggered symptoms of migraine suggest that these brainstem structures are a part of a neuronal network activated during an attack.     

Enhanced microtubule-dependent trafficking and p53 nuclear accumulation by suppression of microtubule dynamics

The tumor suppressor protein p53 localizes to microtubules (MT) and, in response to DNA damage, is transported to the nucleus via the MT minus-end-directed motor protein dynein. Dynein is also responsible for MT-mediated nuclear targeting of adenovirus type 2 (Ad2). Here we show that treatment with low concentrations of MT-targeting compounds (MTCs) that do not disrupt the MT network but are known to suppress MT dynamics enhanced p53 nuclear accumulation, and the activation of the p53-downstream target genes. p53 nuclear accumulation required binding of MTCs to MTs and enhanced the induction of p53-up-regulated modulator of apoptosis (PUMA) mRNA and apoptosis on challenging cells with the DNA-damaging drug adriamycin. Low concentrations of MTCs enhanced the rate of movement of fluorescent Ad2 to the nucleus and increased the nuclear targeting efficiency of Ad2. We propose that suppression of MT dynamics by low concentrations of MTCs enhances MT-dependent trafficking toward the minus ends of MTs and facilitates nuclear targeting.     

Dynamic MRI after surgical repair for pelvic organ prolapse

PURPOSE: The purpose of this work was to compare dynamic MRI measurement results from patients with pelvic organ prolapse before and after surgical repair and to correlate postoperative MRI findings with the results of physical examination and patients' complaints. MATERIALS AND METHODS: Thirty women were included in this prospective study. Fifteen patients with uterovaginal or vaginal vault descent and 15 asymptomatic female volunteers underwent dynamic MRI using a single-shot, fast spin-echo sequence with half-Fourier data acquisition. Single-slice midsagittal images of pelvic organs were obtained at maximal pelvic strain and at perineal contraction. Dynamic MRI was repeated on all patients 2-4 months after surgical repair. Postoperative and preoperative dynamic MRIs were compared with the normal values of the volunteer group. Postoperative MRIs were correlated with the clinical findings after surgical repair. RESULTS: Seven patients reported symptoms after surgical repair, although only two had pathologic findings on physical examination (residual urine associated with third-degree stress urinary incontinence, and bladder neck descent). MRI showed pathologic changes in five of these patients. Two patients with persistent first-degree stress incontinence had no pathologic findings on MRI. CONCLUSION: Dynamic MRI is helpful in the evaluation of persistent patient complaints after surgery for pelvic organ prolapse and detects more defects than physical examination does.