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Malaria, a common health problem in certain parts of the world, has a considerable morbidity and mortality. This work reports under electron microscopy studies serious ultrastructural kidney damage such as extensive cytoplasmic vacuolation, vesiculation and autophagic vacuoles in proximal tubular cells. A thickened endothelial wall on peritubular capillary, interdigitation disorganization and significant decrease of their number in some areas were detected. Swollen rough endoplasmic reticulum, swollen mitochondria, and parasitized erythrocytes were observed. Many epithelial cells exhibited cytoplasmic areas of autophagia and a myelin-like form. A tubular cell presented severe cytoarchitecture alterations. Abundant lipid droplets were noticed. Almost total loss of interdigitations, rough endoplasmic reticulum vesiculation, peritubular capillaries with endothelial cells thickened cytoplasm, papillary processes projected to the lumen, and an inflammatory infiltrate of macrophages were also observed. These ultrastructural kidney changes could cause, on the basis of their clinical and pathologic expressions, a fat accumulation, an acute temporary reversible glomerulonephritis, a chronic progressive irreversible glomerulonephritis, and an acute renal failure (ARF).

Biopsy specimens of cervico-scutular muscles obtained from animals injected with bee crude venom were prepared for electron microscopy studies. At 6 h from Apis mellifera venom injection, in mice under transmission electron microscopy, the muscular fibres presented different atrophy levels with increment of the intermyofibrillar spaces. Tubules and sarcoplasmic reticulum elements were altered, in some places only tubular fragments and an increment of the intermyofibrillar spaces were noticed as well as loss of fibre regularity and prominent triads. In subsarcolemma region, areas lacking myofibrils and mitochondria damages were observed. Muscular segmental necrosis and atrophy areas were observed. Neuromuscular junctions were altered. The number of synaptic vesicles was very variable and synaptic clefts showed irregularities. A decrease in the number and arrangement of the synaptic clefts, as well as free polysomes, suggesting regeneration processes, were also observed. The myelinic nerves exhibited in the axon or in the wall vacuolisation areas. The presence of severe muscular lesions, the finding of venom activities in the presynaptic region and the detection of damages in the neuromuscular junctions at different chronological stages of our experiments indicate that the bee venom is highly toxic for neuromuscular structures.

Bee accidents incidence is underestimated because many people do not consult to the physicians. Here it is described for the first time the severe mice adrenal gland damage induced by Apis mellifera venom. Biopsy specimens were obtained from mice adrenal gland and after sample preparation observed in Hitachi H-7100 electron microscope. In this work the ultrastructural analysis showed, 6 h after injection, a non homogeneous smooth endothelial reticulum, and in some places loss of plasma membrane. The fenestrae spaces were bigger and detritus in the capillary lumen were observed. Erythrocytes were seen in a cortical cell. After 48 h of venom injection, expanded fenestrae were observed. Capillary basal membrane was interrupted. Myelin-like figures and autophagic vacuoles were noticed. Swollen smooth endoplasmic reticulum elements and endothelial unfolding to the light were seen. Moreover, swollen Golgi and mitochondria were observed, in some places forming myelinic-like figures. At 144 h after venom injection, widened spaces were noticed in capillary fenestrae. Cellular section showed swollen and lost smooth endoplasmic reticulum elements. Smooth endoplasmic reticulum tubules disappearance suggested non steroidogenesis. In conclusion, we suggest that some of the bee envenoming human clinical manifestations, as is observed in mice, are determined by suprarenal gland damage produced by toxins present in this venom.

An electron microscopic study of skeletal muscle biopsies from euthyroid and hypothyroid patients with autoimmune thyroid disease (ATD) showed the existence of capillary alterations and a mononuclear cell infiltrate. Microvascular abnormalities included thickening and lamination of basement membrane, endothelial proliferation with progressive lumen occlusion, and hypertrophied pericytes. Capillary degeneration was also observed. Macrophages, and scarce lymphocytes and mast cells formed the cell infiltrate. This pathological picture is similar to that found in the muscular compromise of other autoimmune diseases, particularly Graves' hyperthyroidism. This study shows that patients with ATD may have skeletal muscle capillary abnormalities that could probably be related to autoimmunity and are independent of thyroid functional status.

Investigation of the pathogenesis of human pulmonary damage caused by the toxic aggression by Tityus discrepans venom relies to a considerable extent upon the use of animal models. In this work, authors examine the correlation of clinical manifestations and changes in the organisation of cellular and subcellular pulmonary components in the murine model that probably resembles the damage found in envenomed humans. To evaluate lung subcellular response to Tityus discrepans venom, male C57/Bl adult mice were randomised into two groups: envenomed mice were intraperitoneally injected at a dose of 5 mg/Kg of weight and controls received saline solution. Lung samples were processed by electronic microscopy techniques and observed in a Hitachi-300. Ultrastructural findings in pulmonary tissue showed a partial denudation of its epithelial cells; the basal membrane was irregular and swollen. In the interstice there were fibroblasts with multiple cytoplasmatic projections and abundant extracellular material. Adjacent to the interstice bronchiolar areas with cells showing disperse nuclear chromatin were appreciated. There were losses of the intercellular unions and a clear separation among the cellular plasmatic membranes was observed. In conclusion, we suggest that some of the clinical manifestations of scorpion envenoming may be determined by ultrastructural lung damage produced by toxins present in this venom.

In this work we have studied the cardiologic clinical manifestations appearing in response to toxic aggression by Tityus discrepans venom, such as hypertension, hypotension, tachycardia and pulmonary acute oedema. These depend on changes in the organisation of cellular and subcellular components of cardiac tissues and probably correspond with the damage found in envenomed humans. To evaluate cardiac tissue subcellular response to Tityus discrepans venom, male C57/B1 adult mice were randomised into two groups: envenomed mice were intraperitoneally injected at a dose of 5 mg/Kg of body weight and controls received saline solution. Samples from cardiac tissue were prepared for electron microscopy study and observed in a Hitachi-300. The most relevant cardiac ultrastructural findings in this model showed diffuse disarray of the myofibrils and abnormal pattern of the bands in the sarcomera, contractile element disorganisation, degeneration of fibres and loss of the characteristic sarcomeric structure given the appearance of a lax tissue. One of the most prominent features was the presence of a remarkable perinuclear oedema and the perinuclear cistern exhibited indentations over its whole arrangement. The vascular endothelium of the microvessels exhibited alterations with evident cytoplasmic projections toward the lumen of the vessel. Mitochondria presented a condensed conformation. All findings were degenerative signs of the contractile apparatus. We suggest that any cardiac tissue damage produced by toxins present in this venom are responsible for some of the clinical manifestations in envenomed animals and patients.

In this work we have studied the possible relationships between clinical manifestations such as sialorrhea, appearing in response to the toxic aggression by Tityus discrepans venom, and the alterations or changes at cellular or subcellular levels in sub-maxillary salivary glands in the murine model. To evaluate salivary gland subcellular response to Tityus discrepans venom, male C57/Bl adult mice were randomised into two groups: a group of mice were intraperitoneally injected with Tityus discrepans venom at a dose of 5 mg/Kg of weight and controls received saline solution. In the salivary glands from the envenomed animals sub-cellular changes such as hyperchromatic nucleus, swollen rough endoplasmic reticulum, granules of different electron density, some of them practically transparent, nucleolus of low density and big size and electron-transparent cisterns were observed. Capillary wall was augmented in certain areas and thin in others. Endothelial cell infolding to the lumen was seen. The distribution of the vesicles and its density varied. Macrophages and plasmocytes were observed next to the damaged capillaries. Different electron density of cytoplasm was noticed. In conclusion, we suggest that sialorrhea is determined by salivary gland damage produced by toxins present in this venom.

In this ultrastructural study we examined skeletal muscle fibres from mice intraperitoneally inoculated with a sublethal dose of Crotalus vegrandis (rattlesnake) venom. The group of mice inoculated presented neurological symptoms characterised by respiratory failure and hind limbs paralysis. Skeletal muscle fibres showed different degrees of alterations. Most of them presented the characteristic pattern of necrosis in progress. Atrophied and hypercontracted fibres were frequently seen. Some atrophied and necrotic fibres showed several nucleoli-like bodies in the nucleus. In the atrophic and hypercontracted fibres, sarcoplasmic vacuolation and abnormal mitochondria with stacked cristae were observed. Areas of segmental necrosis were also frequently found. In connection with these altered muscle fibres, capillary abnormalities were detected. This study suggests that in envenomed mice respiratory failure symptoms may be related with muscle damage caused by Crotalus vegrandis venom components.

In South America rattlesnake venom activities have not been entirely characterised. Some studies have shown haemorrhagic, myotoxic, and neurotoxic effects as manifestations of envenoming in experimental animals and humans. Biopsy specimens were obtained from liver and immediately fixed in situ and observed in Hitachi H-500 and H-7100 electron microscopes. In this work the ultrastructural analysis of experimental mice liver showed hepatocytes with increased lipid droplets content and significant vacuolation in areas of their cytoplasm limiting with the Disse space. Lysosomes and altered peroxisomes exhibiting a very dense electron content were also evident. Mitochondrial pleomorphism including cup-shaped and ring-shaped mitochondria were frequently found. The cristae were scarce or absent in the majority of mitochondria observed. The rough endoplasmic reticulum showed a preferentially disposition lining the outer mitochondrial membranes. In some section glycogen particles were scarce and lipofuchsin granules could be observed. Red blood cells showed endothelial cell adherence and, in many instances, the liver sinusoids were observed plugged with aggregated red blood cells. In conclusion, using an animal model that probably correlates well with the pathological effects found in envenomed humans, we have shown the severe hepatocellular alterations caused by this venom.

The symptoms of scorpionic envenomation in mice appear almost immediately after intraperitoneal injection and are manifested by great agitation, hair bristling, accelerated respiration, salivation and lacrimation, vomits and diarrhoea. In this work we intend to correlate those clinical manifestations appearing in response to the toxic aggression by Tityus discrepans venom, to the cellular or subcellular alterations produced in the mouse pancreas, probably similar to those damages found in envenomed humans. To evaluate pancreas subcellular response to Tityus discrepans venom, male C57/Bl adult mice were randomised into two groups: envenomed were intraperitoneally injected (hypochondrial left region) at a dose of 5 mg/Kg weight and controls received saline solution. Samples after preparation were studied in a Hitachi-300 transmission electron microscope. The most relevant ultrastructural changes in pancreatic tissues were an increase in the nuclear heterochromatin, with a corresponding decrease of euchromatin. In the cytoplasm, rough endoplasmic reticulum exhibited zones of oedema, losing its organised aspect. The secretion granules presented smaller electron density and variability in dimensions. At higher magnification a nucleus with picnotic appearance, with indentation of its perinuclear cistern was observed. There was a mitochondrial degeneration, with destruction of the mitochondrial matrix and autophagic vacuoles in its interior. At 48 h the lesions became intensified, with an evident increase in the intercellular spaces.

As liver can be an important target organ in malaria, we performed an ultrastructural study of hepatic alterations in the final stage of Plasmodium berghei infection in mice. Significant hepatocyte abnormalities were found. An elevated number of cells showed mitochondria with a high electron-dense matrix and multiple changes in shape and size, alterations in the structure of Golgi complex, swelling and disorganisation of both rough and smooth-surfaced endoplasmic reticulum, differently shaped peroxisome nucleoids, and disappearance of glycogen granules. In other areas the hepatocytes were significantly altered with diminished microvilli and exhibited myelin-like figures, autophagic vacuoles, abundant lipid droplets, and swollen mitochondria in their cytoplasm. Necrotic and atrophied hepatocytes with scarce microvilli in the Disse space and biliary canaliculi could be seen. Parasitised red blood cells and parasite debris were found inside degenerated hepatocytes. Alterations were also noticed in microvasculature, including thickened endothelial cells with swollen mitochondria, lysosomes and autophagic vacuoles in their cytoplasm. Our results demonstrate that hepatocyte damage is an important finding associated with the advanced stages of P. berghei malarial infection, which may lead to liver dysfunction in this disease.

The ultrastructural study of adrenal cortex from Plasmodium berghei infected mice showed different degrees of capillary wall alterations including disruption and widening of the fenestrae, capillaries packed with parasitized erythrocytes, necrosis of cortical cells, parasitized erythrocytes outside capillaries and in some instances inside cortical cell cytoplasm. Lymphocytes were also observed in degenerated cortical cells. Our results suggest that adrenal cortex lesions may be relevant in the etiopathogenesis of severe malaria.