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Consecuencia de la informalidad en la economía.

Grafica 4 Indicadores de pobreza en el Estado de Puebla (2010)

1.5 Consecuencia de la informalidad en la economía.

Other abnormal features include short apparently normally myelinated internodes in continuity with remyelinating intemodes proximally and distally. The paranodal bulbs o f the intemode with normal myelin thickness show considerable infolding and occasional osmiophillic globules within the Schwann cell cytoplasm (Hall 1973). Irregularities o f the myelin sheath thickness along the remyelinating internode particularly near the Schwann cell nucleus are seen (Hall 1973). Node-like discontinuities in the remyelinating sheath are frequently observed in perinuclear regions (Hall 1973).

5.9 MULTIPLE EPISODES OF DEMYELINATION

The most prominent finding in nerves that have undergone episodes of multiple injury is an increased number of Schwann cells (Hall 1984; Ohara & Ikuta 1988; Thomas 1970). Ohara and Ikuta (1988) studied the effects of multiple crush injuries on the phrenic nerve of young adult mice. The number of Schwaim cell nuclei (SON) increased with each successive crush reaching 10-15x their normal value after 4 successive crushes on the same site. In all crushes 70-80% of the Schwaim cell nuclei were supernumerary and most of these were found as part of onion-bulb formations. Basal laminal onion bulbs were also seen.

Thomas (1970) examined multiple crush injury (up to 9X) in the peroneal nerve of rabbits and also found a progressive increase in the numbers of SCN with successive crushes. In contrast to Ohara and Ikuta's study, Thomas found that ‘clusters’ of Schwaim cells formed longitudinal columns in the nerve and did not form ‘onion bulbs’.

Hall (1984) looked at the effect of multiple intraneural injections of lysophosphatidylcholine (LPC) in adult mouse tibial nerve. Following intraneural injections of LPC the myelin sheath undergoes a characteristic progressive vesicular breakdown, while the axon and the Schwann cell apparently remain undamaged (Hall & Gregson 1971). In singly injected nerves a moderate proliferation of Schwann cells is seen (60% of which are supernumerary Schwann cells (SSC)). These SSC progressively disappeared and by 240 days many remyelinated axons were found surrounded by empty basal laminal tubes, or by double or single fragments of basal lamina (Hall 1973). Following multiple LPC injections the pattern of myelin breakdown was essentially similar to that seen in single injected nerves but the time course differed. The early phases of repair, from the initiation of myelinolysis to the appearance of promyelinated fibres, were achieved more rapidly in multiple injected nerves. During days 5- 10 post injection this early lead was reversed. The majority of axons in 8X injected nerves

were still either promyelinated or associated with debris laden cells, presumably Schwann cells, within the basal lamina. During the first three days post injection most SSC within the lesion had disappeared, although their basal laminae remained in close association with the demyelinating axons. This is interesting in view of the assumption that repeated episodes of demyelination and remyelination will produce layers of Schwann cell cytoplasm around the axon in the form of onion bulbs, and may explain why onion bulbs were not seen in this study.

The effects of the initial demyelination produced by LPC were exacerbated in multiple injected nerves by a local, self limiting, immune mediated demyelination. The presence of macrophages in these lesions suggests that either the cells or some factors released by them may play a role in initiating myelin damage. Compartmentalisation of the endoneurium by fine cytoplasmic processes of perineurial cells was a feature of multiple injected nerve (Hall 1984; Hall 1983). It occurred in some nerves injected 4 times and in most injected 8 times.

The cytoplasmic processes frequently enclosed axons, either singly or in small groups of two or three.

Chapter 6 Materials and Methods

6.1 THE BREEDING COLONY

Proven breeding pairs of Trembler-J mice were imported from Jackson laboratories (USA). The semidominant r / gene was maintained in animals of the C57BL/6 strain and was linked to a rex (Re) coat marker. Both heterozygous and homozygous Re animals should have curly whiskers and a wavy coat (Carter 1951; Crew & Auerbach 1939). The waviness of the coat disappears in adults, but the vibrissae and guard hairs remain curly (Carter 1951; Crew & Auerbach 1939). The Re gene is a dominant and is located on chromosome 11. It is known to be 23 recombination units away from the Tr gene on linkage group five (Falconer & Sobey 1953). Falconer (1953) estimated that 15% of animals with the Re phenotype would not be affected. This was confirmed by Low (1976b) who found that 15% of animals that were phenotypically Re at birth were subsequently found not to be carrying the Tr mutation. Specific linkage data for the Tr^ is not available but as the mutation is located on the same gene as Tr we have assumed that these figures also apply to T / . The Re gene should allow recognition of animals carrying the F / gene; this was intended to be used before the clinical syndrome become apparent.

Six heterozygote T //+ breeding pairs were imported. One affected female died before leaving quarantine. The five remaining pairs were transferred to the RFHSM animal facility. Two of the pairs failed to produce any progeny. The remaining three pairs produced ten, five and two offspring each. The colony was maintained for 4-6 generations on the basis of the

Re coat marker. We were unable to identify curly whiskers in any of the Re animals.

DNA analysis using PCR was established to determine the genotype of animals in the early postnatal stages of development. Initially P7-P10 animals from Re/Re matings were processed for microscopy and tissue taken for DNA analysis. Of the 27 animals examined none were found to be carrying the ZX gene. We then performed DNA analysis on a further 41 Re progeny from 16 breeding pairs, only 4 animals were carrying the T f’ gene. At this stage the use of the Re marker was abandoned and the breeding colony maintained using animals unequivocally showing clinical symptoms at 8 wk of age.

Breeding statistics were compared for ZX and C57BL/6 colonies maintained in the same facility. In breeding pairs where one of the parents was 7X/+, significantly fewer litters were produced per pair than in the control colony. Neither the mean litter size (n) or the proportion of progeny weaned differed between 7 / and control colonies.

Table 6.1 Comparison of the breeding su ccess of Tr^ compared with C57BL/6