Mechanical thrombectomy in acute ischemic stroke due to large vessel occlusion in the anterior circulation and low baseline National Institute of Health Stroke Scale score: a multicenter retrospective matched analysis

Neurological Sciences - The benefit of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) and baseline mild neurological symptoms remains...     

Hematocrit is associated with carotid atherosclerosis in men but not in women

BACKGROUND: It is known that blood and plasma viscosities are associated with clinical manifestations of atherosclerosis, though evidence is not conclusive particularly in women. OBJECTIVE: To verify whether hematocrit and blood and plasma viscosities are independently associated with carotid atherosclerosis and whether their measurement can improve the definition of the global coronary heart disease (CHD) risk. METHOD: Eight hundred and ninety-two participants in a cardiovascular disease prevention campaign were examined with regard to conventional CHD risk factors (age, blood pressure, lipids, glucose, body mass index, waist/hip ratio, cigarette smoking and diabetes), hematocrit and blood and plasma viscosities. According to the degree of carotid atherosclerosis, investigated by echo-Doppler, participants were divided in three groups: those without atherosclerosis, those with a low degree of atherosclerosis and those with a high degree of atherosclerosis. RESULTS: In men, age, blood pressure, intima-media thickness (IMT), hematocrit (47.4+/-3.7%, 47.8+/-3.7%, 48.4+/-3.7%, P<0.05) and blood viscosity (4.69+/-0.51 cP, 4.77+/-0.55 cP, 4.82+/-0.51 cP, P=0.05) increased with increasing degree of carotid atherosclerosis. In women, age, blood pressure, total cholesterol and low-density lipoprotein-cholesterol, IMT and plasma viscosity (1.42+/-0.12 cP, 1.44+/-0.11 cP, 1.46+/-0.13 cP, P<0.05) increased with increasing carotid score. Analysis of covariance (ANCOVA) showed that after adjusting for hematocrit, blood viscosity was no longer different in the three groups. In discriminant analysis, hematocrit, among the hemorheological variables investigated, was independently associated with carotid score in men (F=3.66, P<0.05). Neither hematocrit nor blood and plasma viscosities were significantly associated with carotid score in women. CONCLUSION: These findings suggest that in men, both hematocrit and blood viscosity are related to carotid atherosclerosis but hematocrit would appear to have an independent effect over and above that mediated by viscosity.     

Dosing protocol and analgesic efficacy determine opioid tolerance in the mouse

Rationale  

Analgesic efficacy of opioids and dosing protocol have been shown to influence analgesic tolerance.     

Linkage analysis and disease models in benign familial infantile seizures: a study of 16 families

PURPOSE: Benign familial infantile seizures (BFIS) is a genetically heterogeneous condition characterized by partial seizures, onset age from 3 to 9 months, and favorable outcome. BFIS loci were identified on chromosomes 19q12-13.1 and 16p12-q12, allelic to infantile convulsions and choreathetosis. The identification of SCN2A mutations in families with only infantile seizures indicated that BFNIS and BFIS may show overlapping clinical features. Infantile seizures also were in a family with familial hemiplegic migraine and mutations in the ATP1A2 gene. We have examined the heterogeneous genetics of BFIS by means of linkage analysis. METHODS: Sixteen families were examined. Probands underwent neurologic examination, at least one EEG recording, and, when possible, brain CT and MRI. Clinical information about relatives was collected. Families with SCN2A or ATP1A2 mutations were excluded from the study. Chromosome 16p and 19q loci were examined by linkage analysis using two models that differed in penetrance rate. Genetic heterogeneity was evaluated with both models. RESULTS: Clinical information was available for 124 members of affected families. BFIS was diagnosed in 69 subjects. One patient without BFIS had a single febrile seizure, and another had rare episodes of paroxysmal dystonia. Evidence of linkage was obtained only for chromosome 16. Moreover, the high penetrance allowed the identification of genetic heterogeneity. CONCLUSIONS: Our data confirm the relevance of the chromosome 16 locus in BFIS and suggest the presence of an additional locus. This study shows that the genetic model used affects the outcome of linkage analysis.     

PERIPHERAL NEUROPATHY IN HEPATITIS C VIRUS INFECTED PATIENTS WITH AND WITHOUT MIXED CRYOGLOBULINEMIA

Objective: To evaluate immunohistochemical and ultrastructural changes in sural nerve biopsies from patients with peripheral neuropathy and hepatitis C virus (HCV) infection.
Methods: Frozen and plastic-embedded nerve specimens were obtained from 19 HCV-positive patients with (16) or without (3) mixed cryoglobulinemia (MC). Immunoperoxidase and immunofluorescence studies were performed on cryostat cross-sections using antibodies recognising cellular subsets and humoral factors involved in the inflammation (CD68, CD11a-b-c, CD20, CD3, CD4, CD45, C1q, C3d, TCC, IgG, IgA, IgM). Semi and ultrathin sections were studied by standard protocols.
Results: Nerve biopsy showed an axonal degeneration with micro- angiopathy (perineurial > endoneurial). IgM and IgG were observed as a thin sub-perineurial band and in the wall of endo and perineurial vessels in MC patients only. Immunoglobulin deposition colocalised in some nerves with complement factors. Macrophages and T memory/activated lymphocytes were seen perivascularly and in endoneurium while rare B-cells were detected in perineurium. In the MC-negative patients, the peripheral neuropathy was characterised by a prominent myelin degeneration. The pattern of distribution of immunoreactivity for humoral and cellular factors was similar but not identical to that of MC patients.
Conclusions: Axonal degeneration characterises the HCV-related MC neuropathy and is likely secondary to ischaemia. The vascular damage is prevailing in perineurium and appears to be mediated by both T-cells and immune complex. Myelin alterations mainly occur in MC-negative patients. These last findings suggest a primary pathogenetic role for HCV in the induction of the nerve damage.     

(35)S]GTPγS binding and opioid tolerance and efficacy in mouse spinal cord

The present study examined efficacy of a series of opioid agonists and then using chronic in vivo treatment protocols, determined tolerance to opioid agonist stimulated [³⁵S]GTPγS (guanosine 5′-O-(3-[³⁵S] thio)triphosphate) binding in mouse spinal cord membranes and compared it directly to spinal analgesic tolerance. The [³⁵S]GTPγS binding assay was used to estimate efficacy (E_max and τ; Operational Model of Agonism) of a series of opioid agonists for G-protein activation in mouse spinal cord. The rank order of opioid agonist efficacy determined in the [³⁵S]GTPγS assay using the Operational Model and E_max was similar. These efficacy estimates correlated with historical analgesic efficacy estimates. For tolerance studies, mice were continuously treated s.c. for 7 days with morphine, oxycodone, hydromorphone, etorphine or fentanyl and [³⁵S]GTPγS studies were conducted in spinal cord membranes. Other mice were tested in i.t. analgesia dose response studies (tailflick). Tolerance to DAMGO ([D-Ala²,N-MePhe⁴,Gly-ol⁵]enkephalin) or morphine stimulated [³⁵S]GTPγS binding (decrease in E_max) was observed following etorphine and fentanyl treatment only. These treatment protocols downregulate μ-opioid receptor density whereas morphine, oxycodone and hydromorphone do not. Spinal analgesic tolerance was observed following all treatment protocols examined (morphine, oxycodone and etorphine). Opioid antagonist treatment that specifically upregulates (chronic naltrexone) or downregulates (clocinnamox) μ-opioid receptor density produced a corresponding change in opioid agonist stimulated [³⁵S]GTPγS binding. Although receptor downregulation and G-protein uncoupling are among potential mechanisms of opioid tolerance, the present results suggest that uncoupling in mouse spinal cord plays a minor role and that the [³⁵S]GTPγS assay is particularly responsive to changes in μ-opioid receptor density.     

Differential in vitro neurotoxicity of the flame retardant PBDE-99 and of the PCB Aroclor 1254 in human astrocytoma cells

Polybrominated diphenyl ethers (PBDEs) are an important class of flame retardants. Because of their presence in maternal milk and their structural similarity to polychlorinated biphenyls (PCBs), concern has been raised on their possible developmental neurotoxicity. Aim of the present study was to investigate the in vitro effects of PBDE-99 (2,2', 4,4', 5-pentabromodiphenyl ether) on astroglial cells (human 132-1N1 astrocytoma cells) and comparing it with those of the PCB mixture Aroclor 1254. Both PBDE-99 and Aroclor 1254 caused a concentration-dependent inhibition of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction, however, only the latter increased lactate dehydrogenase (LDH) release or cell death, assessed by the trypan blue assay. PBDE-99 caused translocation of the three protein kinase C (PKC) isozymes (alpha, epsilon, zeta) present in 132-1N1 astrocytoma cells, while Aroclor 1254 affected only PKCalpha and epsilon translocation. However, pre-incubation with the PKC inhibitor GF109203X or PKC down-regulation by the phorbol ester PMA, had minimal or no effect on PBDE-99 or Aroclor 1254-induced cytotoxicity. Similarly, the calcium chelator BAPTA-AM, the tyrosine kinase inhibitor genistein, and the MEK (mitogen activated protein kinase kinase) inhibitor PD98059 had no effect on PBDE-99 and Aroclor 1254 cytoxicity. On the other hand, the phosphatidylinositol 3 kinase (PI-3K) inhibitor LY290042 enhanced PBDE-99 toxicity, but did not affect Aroclor 1254. Because of the involvement of PI-3K in apoptotic cell death, the ability of PBDE-99 and Aroclor 1254 to induce apoptosis in astrocytoma cells was investigated. PBDE-99, but not Aroclor 1254, caused apoptotic cell death in astrocytoma cells, assessed by the TUNEL method and by Hoechst 33258 staining, via a p53 dependent mechanism. These results suggest that PBDE-99 and Aroclor 1254 exert differential cytotoxic effects on human astroglial cells.     

Mediterranean Diet and Fatty Liver Risk in a Population of Overweight Older Italians: A Propensity Score-Matched Case-Cohort Study

Hepatic steatosis, often known as fatty liver, is the most common hepatic disease in Western countries. The latest guidelines for the treatment of nonalcoholic fatty liver disease emphasize lifestyle measures, such as changing unhealthy eating patterns. Using a propensity score-matching approach, this study investigated the effect of adhering to a Mediterranean diet (MedDiet) on fatty liver risk in an older population (≥65 years) from Southern Italy. We recruited 1.403 subjects (53.6% men, ≥65 years) who completed a food frequency questionnaire (FFQ) and underwent clinical assessment between 2015 and 2018. For the assessment of the liver fat content, we applied the Fatty Liver Index (FLI). To evaluate the treatment effect of the MedDiet, propensity score matching was performed on patients with and without FLI > 60. After propensity score-matching with the MedDiet pattern as treatment, we found a higher consumption of red meat (p = 0.04) and wine (p = 0.04) in subjects with FLI > 60. Based on the FLI, the inverse association shown between adherence to the MedDiet and the risk of hepatic steatosis shows that the MedDiet can help to prevent hepatic steatosis. Consuming less red and processed meat, as well as alcoholic beverages, may be part of these healthy lifestyle recommendations.