Carlos Maurício de Castro Costa

APOE4 Protects the Cognitive Development in Children with Heavy Diarrhea Burdens in Northeast Brazil

Polymorphisms in the apolipoprotein E (APOE) have constituted the major rationale to identify potential risk groups for developing late-onset Alzheimers disease and help to predict recovery of cognitive function after brain injury. However, the APOE impact on cognitive development in children living in poor areas of the developing world, where we have discovered profound significant associations of early childhood diarrhea (at 0–2 y) with lasting impairments of growth, cognition, and school performance, is not known. Therefore, we conducted APOE genotyping in 72 Brazilian shantytown children under active surveillance since birth, using purified DNA extracted from buccal cell samples. We found a high frequency of APOE4 alleles (18% versus 9–11% expected) in children with lower diarrhea burdens. When we examined the children who experienced the heavier diarrhea burdens (greater than or equal to the median of seven illnesses in the first 2 y of life), those with APOE4 did significantly better in the coding subtest (p = 0.01) when compared with APOE4-negative children with similar diarrhea burdens. Positive correlations between the APOE4 occurrence and coding scores remained, even after adjusting for family income, maternal education, and breast-feeding. Moreover, the APOE4-positive group, under heavy burdens of diarrhea, had preserved semantic fluency and the mean difference in fluency scores, p = 0.025, a standardized coefficient for disproportional verbal fluency impairment. Our findings show that APOE4 is relatively common in favela children and suggest a protective role of the APOE4 allele in children with a history of heavy burdens of diarrhea in their first 2 y of life.

Use of a generic polymerase chain reaction assay detecting human T-lymphotropic virus (HTLV) types I, II and divergent simian strains in the evaluation of individuals with indeterminate HTLV serology

In countries with a low prevalence of human T‐lymphotropic virus (HTLV) infection, indeterminate HTLV serologies are a major problem in blood bank screening because of the uncertainties about infection in these cases. The recent discovery of two new types of simian T‐lymphotropic virus (STLV), which give an HTLV‐indeterminate serology, raises the question whether indeterminate serologies in humans may be linked to new types of HTLV. Starting from a Tax sequence alignment of all available primate T‐cell lymphotropic virus strains (PTLV), including the two new types STLV‐PH969 and STLV‐PP1664, we developed generic and type‐specific nested polymerase chain reactions (PCRs). The generic PCR proved to be highly sensitive and cross‐reactive for all four types of PTLV, while the discriminatory PCRs had a high sensitivity and a specificity of 100%. There was no cross‐reactivity with human immunodeficiency virus (HIV), ensuring correct interpretation of results from coinfected patients. Among the 77 serologically indeterminate samples tested, 6 were found to be HTLV‐IPCR positive and 1 was HTLV‐II PCR positive. Sequencing of one of the HTLV‐I PCR positives excluded PCR contamination, and revealed a divergent type of HTLV‐I. The majority of the seroindeterminate samples (91%) were however HTLV‐PCR negative, and no new types of HTLV were found. This new assay can identify otherwise undetected HTLV‐I or HTLV‐II infections and is a useful tool of screening for new types of HTLV among seroindeterminate samples. J. Med. Virol. 52:1–7, 1997.© 1997 Wiley‐Liss, Inc.

Application of International Classification of Functioning, Disability and Health (ICF) in individuals with spinal cord injury

UNLABELLED After spinal cord injury is common functionality is affected. OBJECTIVE To evaluate the functionality of patients with spinal cord injury. METHOD Cross-sectional study by means of the International Classification of Functionality (ICF). 109 adults with spinal cord injury in the city of Curitiba, Brazil were evaluated. RESULTS The categories most compromised in body were intestines and bladder, sexuality, energy, sleep, emotion and weight. In the domain activities and participation, there was greater difficulty in tasks of bathing, toilet and dressing, self care and leisure. In the domain environmental factors, the categories classified as facilitators were: medications, orthoses and wheelchair, attitude of family, transport, social foresight and health services. The categories classified as barriers were: attitude of authorities, social attitudes, education and work. CONCLUSION The application of the ICF in persons with spinal cord injury demonstrated a series of disabilities and limitations.

Oral gabapentin treatment accentuates nerve and peripheral inflammatory responses following experimental nerve constriction in Wistar rats

Gabapentin (GBP) is an anti-convulsive drug often used as analgesic to control neuropathic pain. This study aimed at evaluating whether oral GBP treatment could improve nerve inflammation response after sciatic nerve constriction in association with selected pain and motor spontaneous behavior assessments in Wistar rats. We evaluated nerve myeloperoxidase (MPO) and inflammatory cytokines on the 5th day post-injury, time in which nerve inflammation is ongoing. In addition, the role of GBP on carrageenan-induced paw edema and peritoneal cell migration was analyzed. GBP was given by gavage at doses of 30, 60 and 120mg/kg, 60min prior to chronic constriction of the sciatic nerve (CCSN) and during 5 days post-injury, 12/12h. CCSN animals treated with saline were used as controls and for behavioral and inflammation assessments untreated sham-operated rats were also used. On the 5th day, GBP (60 and 120mg/kg) alleviated heat-induced hyperalgesia and significantly increased delta walking scores in CCSN animals, the latter suggesting excitatory effects rather than sedation. GBP (60mg/kg) significantly increased nerve MPO, TNF-α, and IL-1β levels, comparing with the saline group. GBP (120mg/kg) reduced the anti-inflammatory cytokine IL-10 nerve levels compared with the CCSN saline group. Furthermore, GBP (60 and 120mg/kg) increased carrageenan-induced paw edema and peritoneal macrophage migration compared with the CCSN saline group. Altogether our findings suggest that GBP accentuates nerve and peripheral inflammatory response, however confirmed its analgesic effect likely due to an independent CNS-mediated mechanism, and raise some concerns about potential GBP inflammatory side effects in widespread clinical use.

Semantic Fluency: A Sensitive Marker for Cognitive Impairment in Children with Heavy Diarrhea Burdens?

One of the most affected cognitive impairments in children who experienced heavy burdens of diarrhea is semantic fluency, the same impairment that is most affected in Alzheimers dementia. These findings are leading us into provocative genetic studies that may elucidate the evolution of such genetic polymorphisms as the APOE alleles. Alternatively, diarrhea could launch the cognitive deficits that might later progress in neurodegenerative diseases. In addition, they suggest that semantic fluency could provide a simple mean to assess cognitive impairment in impoverished settings so as to determine preventive measures.

Western blot seroindeterminate individuals for human T-lymphotropic virus I/II (HTLV-I/II) in Fortaleza (Brazil): a serological and molecular diagnostic and epidemiological approach.

How to handle Western blot (WB) seroindeterminate individuals for Human T-lymphotropic Virus 1/2 (HTLV-1/2) constitutes a challenge for blood banks and families. We made a cross-sectional study of 191 enzyme linked immunoassay (EIA) reactive individuals from the hematological center (HEMOCE) of Fortaleza (Brazil), examining their serological (WB) and molecular (PCR) diagnosis, and demographic profiles, as well as a possible association of their condition with other infectious pathologies and risk factors. Ethical institutional approval and personal consent were obtained. Out of 191 EIA reactive individuals, 118 were WB seroindeterminate and 73 were seropositive for HTLV-1/2. In the PCR analysis of 41 WB seroindeterminate individuals, 9 (22%) were positive and 32 (78%) were negative for HTLV-1/2. The demographic analysis indicated a trend towards a predominance of males among the seroindeterminate individuals and females in the seropositive ones. The seroindeterminate individuals were younger than the seropositive ones. We did not find any association of these conditions with syphilis, Chagas disease or HIV or hepatitis, and with risk factors such as breast-feeding, blood transfusion, STD (syphilis) and IDU.

Discrepancy, coincidence or evidence in chronic idiopathic spastic paraparesis throughout the world: a meta-analysis on 2811 patients

HTLV-I has been associated with a chronic idiopathic spastic paraparesis (CHISPA) in man; however, a complete understanding of this association is still debated. We selected the most comprehensible papers on this topic between 1985 and 1996, and found that 1261 out of 2811 patients (44.9%) reported, throughout the world, were HTLV-I positive. The mean age was 39.5 years and there was a female predominance of 1.9:1. These results do not exclude the causality of HTLV-I as a germen associated to CHISPA; however, other causes (e.g., toxic, immunosuppressors) must be considered as participating in the multistep neurodegeneration observed in CHISPA throughout the world.

Neuropathic pain characteristics in patients from Curitiba (Brazil) with spinal cord injury

This was a descriptive cross-sectional study on patients with spinal cord injuries living in Curitiba, Paraná, Brazil. The aim was to evaluate the pain characteristics among such patients seen at referral care centers for spinal cord injury patients in Curitiba. A total of 109 adults with spinal cord injury in this city were evaluated regarding the presence of pain, especially neuropathic pain. Neuropathic pain was evaluated using the DN4 questionnaire, a universal instrument that has been translated and validated for Portuguese. A visual analog scale (VAS) was used to evaluate the intensity of pain. The prevalence of pain among these 109 patients was 31.2% (34 patients). The nociceptive pain presented was classified as musculoskeletal pain (nine patients), visceral pain (four patients) and mixed pain (one patient), thus totaling 14 patients (12.8%). Another 20 patients (18.3%) showed symptoms of neuropathic pain and fulfilled the criteria for neuropathic pain with scores greater than 4 out 10 in the DN4 questionnaire. Regarding the characteristics of the patients with neuropathic pain, most of them were male, younger than 40 years of age and paraplegic with incomplete lesions. They had become injured from 1 to more than 5 years earlier. The predominant etiology was gunshot wounds, and the intensity of their pain was high, with VAS scores greater than 5. This study partially corroborates other studies conducted on this subject. Studies of this type are important for understanding the profile of these patients, for the purpose of designing strategies for their rehabilitation, with a focus on the appropriate treatment and management of pain.

Myasthenia gravis in Ceará, Brazil: clinical and epidemiological aspects

A retrospective chart review was performed on patients diagnosed as having myasthenia gravis in Ceará State, Brazil and who were followed from October 1981 to June 2009. Clinical and epidemiologic aspects were evaluated. In this work, 122 patients were studied, of whom 85 (69.7%) were females and 37 (30.3%) were males. The disease duration ranged from five months to 50 years (8.9±8.1 years). Age at the first symptoms varied from 0 to 74 years (31.9±14.4 years). The first main symptoms and signs were ptosis, diplopia and limb weakness. Generalized myasthenia was the most common clinical presentation, but 5.1% (n=6) persisted as ocular myasthenia. Thymectomy was performed in 42.6% (n=52) of myasthenic patients. A thymoma was present in 10 patients. Serum acetylcholine receptor (AChR) antibodies were present in 80% (n=20) of specimens tested. The data presented are similar to those of studies performed in other countries.

Pharmacological, morphological and behavioral analysis of motor impairment in experimentally vitamin C deficient guinea pigs

The scurvy shows an inflammatory disease and gingival bleeding. Nevertheless, in an animal model for guinea pigs, described by Den Hartog Jager in 1985, scurvy was associated with a motor neuron disease with demyelinization of the pyramidal tract, provoking neurogenic atrophy of muscles. Aiming at searching the protective role of vitamin C in nervous system, a pharmacological, morphological and behavioral study was conducted. Three experimental groups were used: A100, animals receiving 100 mg/ vitamin C/ day; A5.0, animals receiving 5.0 mg/vitamin C/ day; and A0, animals without vitamin C. We analyzed the weight gain, muscular diameter and behavioral tests. In all tests examined, we found significant differences between the supplemented groups in comparison with scorbutic group (p<0.05). Thereafter, the animals were killed for histopathology of gastrocnemius muscle, spinal cord and tooth tissues. In addition, a morphometric study of periodontal thickness and alpha-motor neuron cell body diameter were done. The vitamin C-diet free regimen seemed to induce a disruption in spinal cord morphology, involving the lower motor neuron, as confirmed by a significant reduction in neuron perycaria diameter and muscular atrophy, complicated by increased nutritional deficit.