Histopathology of experimental myiasis in mice as a result of infestation and experimental implantation of Dermatobia hominis larvae.

A laboratory model of myiasis as a result of Dermatobia hominis (L.) larvae was developed using mice as hosts. Mice in three groups were each infested with one newly hatched larva and skin biopsies processed for histopathology at 4, 12, and 20 d postinfestation (dpi). Mice in three other groups were each subjected to implantation of one larva collected from an infested (donor) mouse at 4, 12, and 20 dpi. Skin lesions of these receptor mice were then assessed at 10, 14, and 6 d postimplantation (dpimp), respectively. The inflammatory process in infested mice at 4 dpi was discrete, consisting of a thin necrotic layer around the larva, edema, many neutrophils, few eosinophils, mast cells, and proliferation of fibroblasts. At 12 dpi, there was a thicker necrotic layer, edema, many neutrophils and eosinophils, few mast cells, neoformation of capillaries, proliferation of the endothelium and fibroblasts, and early stages of fibrosis. These histopathological characteristics together with fibrosis were observed over a large area of the lesion at 20 dpi. Mice submitted to larval implantations demonstrated similar skin histopathology to that seen in the infested rodents, 10 dpimp corresponding to 12 dpi and 6 or 14 dpimp to 20 dpi. In all mice, the progressive acute inflammatory process followed a sequence linked to factors such as size of larvae and presence of secretory-excretory products. Both infested mice and those implanted experimentally with D. hominis larvae were shown to be suitable models for the study of the parasite-host relationship in this important zoonotic myiasis.

Soluble inflammatory markers as predictors of liver histological changes in patients with chronic hepatitis C virus infection.

Host immune response seems to be mainly responsible for the progression of liver disease among patients with hepatitis C virus (HCV) infection. Immune activation involves the release of cytokines and their receptors that can be measured in plasma samples. The study aimed to evaluate the association between plasma levels of chemokines and soluble tumor necrosis factor receptors (sTNFR) and liver histological changes among patients with chronic HCV infection. Seventy-one treatment-naive patients were included. Plasma levels of CCL2, CCL3, CCL11, CCL24, CXCL9, CXCL10, sTNFR1, and sTNFR2 were measured and liver histological findings were reviewed. Plasma levels of CXCL9, sTNFR1, and sTNFR2 were significantly associated with liver fibrosis, with higher median levels found among patients with moderate/severe fibrosis (F >or= 2) if compared to those with no or mild fibrosis (p = 0.014; p = 0.012; p = 0.009, respectively). Plasma sTNFR2 levels were significantly associated with necroinflammatory activity, with higher median levels among patients with moderate/severe activity (A >or= 2) if compared to those with no or mild activity (2.34 ng/mL vs. 1.99 ng/mL; p = 0.019). In conclusion, plasma levels of CXCL9, sTNFR1, and sTNFR2 were independently associated with liver histological changes, suggesting a role of TNF activation and Th1-type cell-mediated immune response in the pathogenesis of HCV infection.

Lymphadenopathy and expression of nodal mast cells and eosinophils in the myiasis by human bot fly.

Wistar rats (Rattus norvegicus) infested with Dermatobia hominis (L. Jr., 1781) had their axillary lymph nodes removed and histopathologically processed. Follicular hyperplasia in the germinal center was noted from 2 d postinfestation (dpi), exhibiting a high number of centerblasts, mitotic and apoptotic cells, and a thin parafollicular area. The paracortex showed hyperplasia rich in dendritic cells, immunoblasts, and endothelial venules, with diapedesis seen from 4 dpi onward. Hyperplasia of the medullar sinus also was first observed at this point, as well as dilated lymphatic sinus, lymph, macrophages, neutrophils, mast cells, and eosinophils. Medullar strings were expanded and filled with immunoblasts, mitotic cells, and plasmocytes. Lymphadenitis was not observed. The expression of mast cells was similar for both myiasis-affected and control rats but increased significantly (mastocytosis) at 7 and 15 d postlarval emergence (dple). Eosinophilia was observed at 4, 10, 15, 20, and 28 dpi as well as at 2, 7, and 15 dple, particularly on the last three observations of dpi and the earliest dple. This experimental approach allowed progressive tissue reactions in the lymph nodes to be monitored during myiasis, particularly those involving mast cells and eosinophils. These reactions abated and complete repair was observed at 60 dple.

Experimental skin lesions from larvae of the bot fly Dermatobia hominis.

Skin biopsies from larvae of Rattus norvegicus, experimentally infested with Dermatobia hominis (Linnaeus Jr) (Diptera: Cuterebridae), were processed for histopathological studies. Two days after infestation, the first-stage larvae (L1) were located deep in the dermis, surrounded by an inflamed area infiltrated predominantly by neutrophils. On the fourth day a thin necrotic layer could be seen close to the larvae, surrounded by large numbers of neutrophils, lymphocytes, macrophages with a few eosinophils and mast cells. A small warble was formed after the fourth day, increasing in size until the seventh day, when the L1 moulted to the second-stage larva (L2). The inflammatory process continued with increasing numbers of neutrophils, macrophages, lymphocytes, eosinophils and mast cells invading the area, as well as the proliferation of fibroblasts and endothelial cells and the appearance of a few localized haemorrhages. After 18-20 days, the L2 moulted to the third-stage larva (L3), when a few plasma cells could be seen in the inflamed area. At 25-30 days there was a reduction in the necrotic layer, as well as in the number of neutrophils and lymphocytes, although large amounts of eosinophils, plasma cells, and collagen fibres were seen. The L3 usually left the host after 30 days. Two days later, the larval cavity was reduced, mast cells infiltrated the region and collagen fibre production were increased. After 7 days, an intense infiltration of plasma cells and scattered necrotic areas could be seen. A scar formed after 10 days. This study showed the laboratory rat to be a suitable model for studies of D. hominis infestation.

An unusual case of papillary carcinoma of the thyroid with cutaneous and breast metastases only.

Cutaneous metastases of thyroid carcinoma are infrequent and, when present, are usually located in the vicinity of a widespread primary tumor. Breast metastases from these tumors are even less common. We report the case of a 64-year-old female with a toxic multinodular goiter in whom a fine-needle biopsy, performed in 1985 at the age of 52, was suggestive of papillary carcinoma of the thyroid. Total thyroidectomy for a papillary carcinoma, follicular variant, was performed in 1988. Four months after surgery, a cutaneous metastasis was discovered in the right thigh. Surgical excision of the lesion followed by treatment with radioactive iodine decreased serum Tg levels from 7495 to 3.3 micrograms/l. Under suppressive therapy with L-thyroxine, serum Tg remained undetectable for the next 4 years. Then, serum Tg levels rose to 3.9-5.6 micrograms/l and a second cutaneous metastasis was removed from the abdominal wall. The patient was again treated with radioactive iodine and the post-treatment whole-body scan did not show any area of increased uptake of the radionuclide. However, serum Tg levels under suppression with L-thyroxine remained elevated at 4-20 micrograms/l for the next 2 years. In August 1995, a 1.5 cm nodule was found in the right breast. Cytological examination was suggestive of a breast metastasis from thyroid carcinoma and the lesion was removed by enucleation. This proved to be a metastasis from a papillary carcinoma of the thyroid. Elevated (19-44 micrograms/l) serum Tg levels persisted postoperatively. A third cutaneous metastasis was revealed by 131I scintigraphy in the right buttock and surgically removed in December 1996. Serum Tg levels have remained undetectable since then. To the best of our knowledge, this is a unique case of a papillary carcinoma of the thyroid with a propensity to metastasize only to the skin and breast during a follow-up of 11 years.

Oncocytic adenocarcinoma of the ovary.

A rare case of ovarian adenocarcinoma with extensive oncocytic differentiation is presented. Light and electron microscopy examination and a specific stain for mitochondria (chromotrope-alcian blue) confirmed the diagnosis. The tumour cells revealed abundant granular and eosinophilic cytoplasm containing a large number of mitochondria. The tumour had a malignant infiltrative pattern and cellular atypia.

Hepatic extracellular matrix in BALB/c mice infected with Leishmania donovani.

The development of the extracellular matrix (ECM) in the liver of the BALB/c mouse infected with Leishmania donovani was observed by histology, immunocytochemistry and electron microscopy at 1, 2, 4, 8, 14 and 20 weeks after infection. Collagen III and proteoglycan were detected in granulomas and in the portal spaces from 4 to 20 weeks after infection. Laminin was not detected in granulomas but was observed in the basement membrane of new small blood vessels in the granulation tissue around the portal spaces from 8 to 20 weeks after infection. The ECM components in the space of Disse showed no changes in distribution throughout the entire period of study. Systemic fibrosis in the hepatic lobule was not evident in the BALB/c mice. This mouse strain does not appear to be an appropriate model to study the role of ECM in chronic visceral leishmaniasis.

Mammary adenocarcinoma of viral genesis in CF-1 mice

No biotério de pequenos animais da Fundaçäo Ezequiel Dias verificou-se em camundongos frequência mensal média de 0,83 por cento de nódulos tumorais subcutâneos, entre abril de 1991 e julho de 1992. Os achados macroscópicos e à microscopia óptica e eletrônica foram compatíveis com o quadro de adenocarcinoma mamário de origem viral do tipo MuMTV (Murine Mammary Tumor Virus)

Morphological and morphometric study of atrial specific granules and other secretory components in dogs experimentally infected with Trypanosoma cruzi.

Changes in blood volume can induce morphometric and morphological alterations in the secretory complex of the myoendocrine cells due to the stretching of atrial walls. These alterations were studied by electron microscopy, using dogs infected intraperitonially with Trypanosoma cruzi and necropsied during the acute phase of the infection when congestive heart failure was present. Several changes were observed in the myoendocrine cells of the heart: hypertrophy and hyperplasia of rough endoplasmic reticulum and Golgi complex, increase in telenuclear secretory complex, increase in fusion of type B atrial specific granules (ASG), decrease of the total number of ASG, enlargement of the maximum diameter of type A ASG and a relative increase in the number of type B ASG. These alterations suggest a larger secretory activity of the atrial myoendocrine cells with a larger secretion of atrial natriuretic peptide (ANP).

Scorpion sting-induced pulmonary oedema: evidence of increased alveolocapillary membrane permeability.

A 16-year-old boy died with acute pulmonary oedema and shock after Tityus serrulatus scorpion sting. The patient showed evidence of cardiac dysfunction and damage, an increase in tracheobronchial aspirate/plasma protein concentration, light microscopic features of the lung compatible with the adult respiratory distress syndrome and electron microscopic findings compatible with acute lung injury and increased alveolocapillary membrane permeability.

Sea-blue histiocytosis in a family with Niemann-Pick disease. A clinical, morphological and biochemical study.

Four siblings of a large Brazilian kindred are shown to have a variant of Niemann-Pick disease masquerading as the sea-blue histiocyte syndrome. They show a very similar clinical and laboratory picture: massive hepatosplenomegaly, low height for age, diffuse interstitial pulmonary infiltration, high levels of serum acid phosphatase and sea-blue histiocytes in the bone marrow. The neurological examination, as well as the retinae and maculae are normal. The high-density lipoprotein serum cholesterolemia ranged from 8.6 to 13.9 mg/dl, much lower than the 5th centile of normal distribution. The AI apolipoprotein concentrations in two siblings (0.29 and 0.44 g/l) were also below the minimal reference level of 0.90 g/l. The histochemical reactions demonstrated that sphingomyelin and ceroid are the accumulating substances in the marrow histiocytes. Electron microscopically, the cytoplasmatic granules of the histiocytes are phagolysosomes which contain scarce amorphous material, loose arranged lamellae, or dense well-organized structures with a fingerprint or fine network pattern. The sphingomyelinase activity in leucocyte extracts ranged from 4.9 to 8.6% and in cultured fibroblast extracts from 7.7 to 10% of simultaneous controls. The activity of other lysosomal enzymes was normal. Accordingly, this variant of Niemann-Pick disease should be classified as chronic nonneuronopathic sphingomyelinase-deficient type. The present data suggest that this variant is inherited as an autosomal recessive character. Our findings support the view that the sea-blue histiocyte syndrome is not an independent entity.

Etoposide in the treatment of six children with Langerhans cell histiocytosis (histiocytosis X)

Six children received etoposide as the single agent for treatment of Langerhans cell histiocytosis (LCH; histiocytosis X). Five were less than 2 years old at diagnosis. All had multiorgan involvement; one had liver and pulmonary dysfunction. Two infants also had clinical signs of immune deficiency. Complete response was observed in five. There was no major toxicity. Although three of four evaluable patients relapsed, the drug was considered useful in moving the children from a symptomatic to an asymptomatic clinical status. Etoposide may become a "first-line" drug in the treatment of systemic LCH, especially when the side effects of steroid therapy are considered unacceptable.

Ultrastructure of a spiral micro-organism from pig gastric mucosa ("Gastrospirillum suis").

The ultrastructural features of a helical-shaped bacterium occurring in the stomach of pigs, within the mucus on the mucosal surface of antral pits, were examined. The bacterial cell had three to eight spiral turns, flattened and truncated ends and was approximately 4.0 microns long and 0.6 microns wide. In some sections, up to six flagella, about 22 nm in diameter, were seen arising from each pole. The cytoplasm contained sparse, irregular granules, numerous ribosomes and large single-layered membrane-bound granules. In the flagella insertion area, there was a highly electron-dense component, the "polar membrane". This micro-organism differed from similar bacteria described in cats, dogs and monkeys, and may cause inflammation in the antral mucosa of pigs similar to Helicobacter pylori infection in man. Furthermore, it was morphologically similar to the spiral micro-organism distinct from H. pylori which has been described recently in human antral mucosa from patients with gastritis and may be of potential significance as a pathogen in man. The name "Gastrospirillum suis" is proposed for this bacterium.

Very low levels of high density lipoprotein cholesterol in four sibs of a family with non-neuropathic Niemann-Pick disease and sea-blue histiocytosis.

Very low serum levels of high density lipoprotein cholesterol ranging from 8.6 to 13.9 mg/dl were detected in four out of 12 sibs of a Brazilian kindred with the non-neuropathic form of Niemann-Pick disease. Hepatosplenomegaly, interstitial infiltration of the lungs, absence of neurological signs, sea-blue histiocytes in the bone marrow and liver, and high values for serum acid phosphatase (18 to 32 U/l) were common to all affected children. Leucocyte acid sphingomyelinase activity ranged from 3.6 to 6.5% of mean control values, and fibroblast activity from 9 to 13% of mean controls. The parents had low-normal levels. The relationship between these findings is unclear and deserves further investigation.

[Optical and electron microscopic study of the kidney of dogs naturally and experimentally infected with Leishmania (Leishmania) chagasi]. / Estudo, ao microscópio óptico e eletrônico, do rim de cães natural e experimentalmente infectados com Leishmania (Leishmania) chagasi.

Two naturally infected dogs (male and female) from Teófilo Otoni (MG-Brazil) were maintained for 18 months in our laboratory. Two other dogs, two months old males were infected with 1 x 10(6) promastigotes of MHO/BR/70/BH46 Leishmania (Leishmania) chagasi strain, endovenous route, and autopsied after 10 months and two years. The main findings concerning the kidney were: (1) focal or diffuse mesangial glomerulonephritis with proliferative and enlargement of mesangial cells; (2) increase in thickness of basement membrane with electron-dense deposits; (3) chronic interstitial nephritis with intense exudation of plasmocytes; (4) cloud swelling of renal tubules. The authors discuss the probable pathogenetic mechanisms.

Effect of scorpion toxin on the enterochromaffin-like cells in normal and trypanosoma cruzi-infected rats: a morphological study

A injeçäo intravenosa de toxina escorpiônica ( Tityus serrulatus) en ratos normais e infectados pelo Trypanosoma cruzi näo causou alteraçöes morfológicas ultra-estruturais das células enterocromafins-like (ECL) do estômago, embora tenha induzido a aumento significativo da secreçäo do suco gástrico

Effect of scorpion toxin on the enterochromaffin-like cells in normal and Trypanosoma cruzi-infected rats: a morphological study.

Intravenous injection of scorpion toxin (Tityus serrulatus) in normal and Trypanosoma cruzi infected rats did not cause ultrastructural morphologic changes on enterochromaffin-like (ECL) cells of the stomach, although it induced a significant increase of the gastric secretion. Our data seem to indicate that gastric ECL cells structure is not affected by stimulation with scorpion toxin or by acute infection with T. cruzi in the rat.