Histopathological

Another potential histopathological biomarker of endocrine disruption is the development of ovotestes in the lobster Homarus americanusf... 

Develop biomarkers of endocrine disruption. F iirther evidence of endocrine disruption is required in addition to population parameters. Biochemical and histopathological biomarkers are required to identify which hormone systems are affected. 

Histopathological examination (up to 40 different tissues were post-mortem and examined for abnormality). 

No histopathological changes in midgut epithelium general paralysis or rise in blood pH Germination of spores and multiplication of vegetative bacilli... 

Histopathological examination shows the typical corelike lesions in a high proportion of muscle fibers in older patients this may amount to 100%. Most typically the cores are large and centrally-placed, but multiple cores may occur in the same fiber cross section. Most older patients show a striking predominance of type 1 (slow twitch oxidative) fibers and virtually all fibers with cores are type 1. Sometimes younger family members have more normal proportions of type 1 and type 2 fibers but, again, the cores are confined to the type 1 fibers. It is well established that muscle fiber types can interconvert due to altered physiological demands, and it is likely that fibers with cores convert to a basically slow twitch-oxidative metabolism to compensate for the fact that up to 50% of their cross sectional area may be devoid of mitochondria. 

Histopathological features are dominated by the large number of centrally-placed muscle nuclei, sometimes affecting more than 90% of muscle fibers. The nuclei form long chains in the middle of the fiber and are surrounded by cytoplasm, which contains mitochondria and membranous vesicles, but no myofibrils. This morphological appearance has prompted comparison with myotubes, and in fact centronuclear myopathies are sometimes referred to as myotubular myopathies. This is a misnomer, however, since although the affected fibers retain some of the structural features of myotubes, and maturational arrest may play a role in their formation, the vast majority of such fibers are fully differentiated histochemically into either type 1 or type 2. 

The histopathological features of muscle samples from patients with myotonic dystrophy are not particularly distinctive. Early changes appear to be a selective atrophy of type 1 fibers, and hypertrophy of type 2 fibers, but the biochemical and/or physiological basis of these possibly related phenomena is not known. The incidence of degenerating fibers increases with age, although the presence of internally nucleated muscle fibers in early stages of the disease suggests that the muscle retains... 

Congenital myotonic dystrophy is a relatively rare condition in which myotonia (defined electrically) is mostly absent in the affected newborn infant, but becomes apparent in the older infant. Histopathology shows a consistent feature of arrested development and maturation of muscle fibers, but there is, currently, no adequate explanation for this phenomenon. Patients with congenital myotonic dystrophy rarely survive without aggressive ventilatory support, and survivors, without exception, are severely multiply handicapped. 

The clinical and histopathological features of individual neurogenic muscle disorders are determined to a large extent by the balance of the opposing processes of denervation and reinnervation, at least as far as the muscle dysfunction is concerned. The involvement of upper motor neurons in some of these disorders is outside the scope of this chapter and will only be referred to in passing. 

Juvenile dermatomyositis (JDM) is perhaps the most uniform, in terms of clinical and histopathological features, of the whole PM/DM disease complex. Presentation may be before 5 years of age with peak incidence between 8 and 12 years. The disease may remit and recur until well into young adult life. The skin lesions include a facial rash in butterfly distribution across nose and cheeks. Erythematous skin changes are seen over extensor surfaces of joints, especially knees, knuckles and elbows. Muscle involvement is generally evident some time later and takes the form of weakness and stiffness, particularly affecting shoulder and pelvic musculature. Proximal muscles are often worse affected than distal muscles and extensors worse than flexors. In the absence of prompt and effective treatment contractures may occur at elbows, ankles, knees, and hips. Subcutaneous calcification and skin ulceration may be found calcification of deeper-lying connective tissue may be apparent on X-ray. 

The histopathological features of PM may be radically different from those of JDM and ADM. There is little, if any, evidence of involvement of the micro vasculature and the muscle necrosis which occurs appears to be the direct result of targeting of individual muscle fibers. In the dermatomyositis syndromes, antibody-dependent humoral mechanisms are predominant and B-lymphocytes are seen to be the most abundant cell type in almost all JDM cases and a substantial proportion of ADM cases. In contrast, most muscle biopsies from PM patients show evidence of inflammation in which TS (cytotoxic) lymphocytes predominate (Figure 20). Moreover, the distribution of inflammatory cell infiltrates tends to be different. Instead of the mainly perifascicular location of lymphocytes in JDM/ADM, there... 

The definition of an overlap syndrome dictates that the criteria for diagnosis of both disorders (in the present context, of PM/DM and of some other connective tissue disorder), are fulfilled. It is not unexpected that those syndromes which overlap with PM/DM are also either known autoimmune conditions or ones in which an autoimmune basis is strongly suspected. The association of these disorders with PM/DM syndromes may not materially alter the basic histopathological featmes expected in PM/DM but some differences may be identifiable. The disorders most frequently associated with an overlap syndrome are rheumatoid arthritis, systemic lupus erythematosis, scleroderma, and mixed connective tissue disease. 

This form of myositis stands apart from the classical PM/DM syndromes on account of its distinctive clinical and histopathological features. There is no clear difference in incidence between males and females and the disorder is typically one of middle or old age. In the majority of cases, progression is slow and skin involvement is not seen, so that the main question of differential diagnosis is its distinction from chronic PM. Unlike classic PM, weakness involves distal muscles as frequently as proximal muscles. CK levels are usually only moderately raised. A common finding which leads to the correct diagnosis of this condition is its nonresponsiveness to steroid treatment or other forms of immunosuppression. 

Balb c mice and Wistar rats were used in the experiments. The administration of single doses of 1, 2 and 2 caused mainly necrotic changes in the liver, measured by GPT and histopathology. The extent of necrosis depended on doses and on time of observation (1-4 days after injections). In shorter time interval (2-4 hrs) 1, 2 and 2 caused depletion of hepatic GSH (even up to 10 % of control). 4 and 5 did not generate necrotic changes. Increased GPT activity was observed after 3 doses of fi. Single doses of 4, 5 and fi mostly increased the level of malondialdehyde (MDA-indicator of lipid peroxidation) in the liver. Repeated injections (3-7) of the investigated compounds enhanced the activity of ALA-D or ALA-S in the liver and caused steatosis. 

The histopathological examination of mice liver performed after a single dose of dibromobenzenes shows that 2 and 2 isomers resulted in zonal coagulative or haemorragic necrosis. It affected from 25-50 % to over 50 % of the liver parenchyma (i.e. 4-5 arbitrary units). 4 caused necrosis of only individual hepatocytes. 

Histopathological examination of rats liver carried out after 7-fold administration of the studied compounds points out that the most visible pathological lesion is steatosis of all zones. 

Bromobenzene, similarly to acetaminophen, is considered as model compound in liver necrosis (refs. 9-11, 20, 21). After the administration of these compounds, a considerable decrease in GSH levels, an increase in GTP activity in the serum and, histopathologically, necrosis of hepatocytes are observed. 

No changes in GTP and y-GT activity were recorded after repeated administration of the above compounds. Also, histopathological examination did not point to liver necrosis. Similar phenomenon detected earlier after repeated administration of monobromobenzene, was interpreted as a result of damage of the microsomal enzymatic system responsible for the appearance of active metabolites (ref. 22). 

Schwaiger J, Ferling H, Mallow U, Wintermayr H, Negele R (2004) Toxic effects of non-steroideal anti-inflammatory drug diclofenac. Part I. Histopathological alterations and bioaccumulation in rainbow trout. Aquat Toxicol 68 141-150... 

The database for monomethyltin is not conclusive for neurotoxic effects, and, therefore, a NOAEL could not be determined. However, on the basis of 90-day studies on monomethyltin/dimethyltin mixtures detailing histopathology, dose comparisons between studies on different mixtures suggest that dimethyltin is the predominant active ingredient, and, taking into account structure-activity relationships, it would be expected that the neurotoxicity of monomethyltin is lower than that of dimethyltin. 

Wester PW, Canton JH (1987) Histopathological study of Poecilia reticulata (guppy) after long-term exposure to bis(tri-/7-butyltin)oxide (TBTO) and di-n-butyltindichloride (DBTC). 

Routine gross and histopathological examinations revealed no treatment-related effects on the respiratory system of dogs exposed to 0.03, 0.1, or 0.3 mg/kg/day methyl parathion in the diet for 1 year (Suba 1981). Chronic dietary exposure to methyl parathion did not induce respiratory effects in mice fed 16.2 mg/kg/day or rats fed 2 mg/kg/day (NCI 1979). 

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