Pesticide assessment: Protecting public health on the home turf

Pesticide regulation is examined in the context of Health Canada’s Pest Management Regulatory Agency’s assessment of the chlorophenoxy herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) for turf. 2,4-D is the most common herbicide used to kill weeds in grass.The medical literature does not uniformly indicate harms from herbicides. However, the balance of epidemiological research suggests that 2,4-D can be persuasively linked to cancers, neurological impairment and reproductive problems. These may arise from 2,4-D itself, from breakdown products or dioxin contamination, or from a combination of chemicals.Regulators rely largely on toxicology, but experiments may not replicate exposures from 2,4-D application to lawns because environmental breakdown products (eg, 2,4-dichlorophenol) may not accumulate and selected herbicides are possibly less contaminated. Dioxins are bioaccumulative chemicals that may cause cancer, harm neurological development, impair reproduction, disrupt the endocrine system and alter immune function. No dioxin analyses were submitted to the Pest Management Regulatory Agency, and the principal contaminants of 2,4-D are not among the 17 congeners covered in pesticide regulation. Independent assessment of all dioxins is needed, in tissues and in the environment.The 2,4-D assessment does not approach standards for ethics, rigour or transparency in medical research. Canada needs a stronger regulator for pesticides. Potentially toxic chemicals should not be registered when more benign solutions exist, risks are not clearly quantifiable or potential risks outweigh benefits. Until landscaping pesticides are curtailed nationally, local bylaws and Quebec’s Pesticide Code are prudent measures to protect public health. Physicians have a role in public education regarding pesticides.     

Involvement of the dorsal root ganglion in acute experimental allergic encephalomyelitis in the Lewis rat. A histological and electrophysiological study

Histological and electrophysiological studies were performed in Lewis rats with acute experimental allergic encephalomyelitis (EAE) in order to determine the extent of dorsal root ganglion (DRG) involvement. Histological studies showed inflammation and demyelination in both the central nervous system (CNS) and peripheral nervous system (PNS). The DRG was the most affected region of the PNS and its involvement increased caudally. Nerve conduction abnormalities were demonstrated in the regions of the lumbar, sacral or coccygeal DRGs in some of the rats with EAE. However, the overall DRG involvement was much less severe, both histologically and functionally, than what we recently found in rabbits with EAE. Conduction through the lumbar dorsal root entry zone was normal. We conclude that lesions of the afferent pathway to the spinal cord do not contribute significantly to the disturbances of hindlimb motor function in Lewis rats with EAE.     

Preliminary evaluation of vitiligo using in vivo reflectance confocal microscopy

BACKGROUND: Vitiligo is the most common pigmentary disorder with a global incidence from 0.1% to 2% in different geographical areas. Histopathology and histochemistry have shown the reduction of melanocytes in achromic patches, but microscopic changes of lesional and non-lesional skin are still not completely understood. Reflectance confocal microscopy (RCM), based on the different light reflectance index of cutaneous structures, allowed in vivo, en face microscopic evaluation of superficial skin layers with a resolution similar to skin histology. AIM: The purpose of this study was to evaluate RCM features of lesional and non-lesional skin of vitiligo patients. Moreover, re-pigmented areas were taken into consideration in order to evaluate melanocyte response to ultraviolet B (UVB) radiation. SUBJECTS AND METHODS: Sixteen patients of different phototypes affected by active non-segmental vitiligo and 10 controls were enrolled in the study. In vivo skin imaging was done using a commercially available RCM (Lucid, Vivascope 1500. Re-pigmented areas from 6 to 16 patients (after UVB narrow-band therapy) were also examined. RESULTS: Vitiligo lesions showed the disappearance of the bright rings normally seen at the dermo-epidermal junction. Moreover, non-lesional skin of vitiligo patients showed unexpected changes as the presence of half-rings or scalloped border-like features of the bright papillary rings. In re-pigmented areas after UVB narrow band therapy, the presence of activated, dendritic melanocytes was seen. CONCLUSIONS: Considering our results, and following further studies, RCM clinical applications could be used in the therapeutic monitoring and evaluation of the evolution of vitiligo.     

Haloperidol impairs classically conditioned nictitating membrane responses and conditioning-related cerebellar interpositus nucleus activity in rabbits

Rabbits, chronically implanted with recording electrodes in the cerebellar interpositus nucleus and following acquisition of a classically conditioned eyelid response, were injected with haloperidol (HAL, 250 micrograms/kg). HAL significantly reduced the number of conditioned responses when a 75 and 85 dB tone conditioned stimulus (CS) was presented but not when a 95 dB tone CS was used. There was a corresponding decrease in interpositus activity at the 75 and 85 dB CS intensities but not at the 95 dB intensity. HAL appeared to disrupt CRs and interpositus activity by increasing the intensity threshold of the tone CS for eliciting conditioned responses. Possible mechanisms for the effect of HAL on neural circuitry involved in classical eyelid conditioning are discussed.     

The use of the polymerase chain reaction to map CD4+ T cell epitopes.

CD4+ T cells recognize processed exogenous antigen in the form of peptides bound to syngeneic major histocompatibility complex class II molecules on antigen-presenting cells. We have developed a novel and convenient method to synthesize and map CD4+ T cell epitopes of cloned antigens using polymerase chain reaction (PCR)-directed construction of genes expressing recombinant protein fragments. Unique restriction sites incorporated into the PCR primers were employed for the unidirectional cloning of gene fragments into a bacterial expression vector that can be induced to high-level expression. The bacterial lysate could be used directly in T cell proliferation assays. Overlapping recombinant fragments spanning the entire protein were generated and tested. The length of the sequence containing the epitope was further reduced by utilizing PCR to generate 3' truncations. Finally, a small number of overlapping peptides spanning a sequence of 39 amino acids were synthesized to identify a thirteen-amino acid peptide epitope within chicken transferrin that stimulates the T helper cell clone D10.G4.1. PCR-directed construction of fragments of antigen allows for optimal design of strategies for the mapping and analysis of CD4+ T cell epitopes.