Biomedical subjects

S B Garcia

Publications and source records attributed to S B Garcia.

8 recordsLinked to original sources

PubMed1999

Field cancerization, clonality, and epithelial stem cells: the spread of mutated clones in epithelial sheets.

There has been considerable debate about the origin of human tumours, whether they arise from a single cell and are clonal populations or whether there needs to be some sort of co-operativity between cells for the neoplastic process to begin. Current theories subscribe to the clonal view, where a series of mutations in one cell begins a process of selection and clonal evolution leading to the development of the malignant phenotype. This review approaches this problem by asking how mutated clones, once established, spread through tissues before becoming overtly invasive. While there is substantial evidence in favour of independent origins of each tumour from a unique mutated clone, there are instances where such clones expand and remain cohesive, often involving a large area of tissue. The main example is the movement of mutated clonal crypts through the colorectal epithelium, by the process of crypt fission. In passing, the clonal architecture of early, pre-invasive lesions is examined, often with some surprising results.

Animals↗

PubMed1999

Nitric oxide is involved in the lesions of the peripheral autonomic neurons observed in the acute phase of experimental Trypanosoma cruzi infection.

Our aim was to investigate the possible involvement of nitric oxide (NO) in peripheral denervation during the acute phase of murine experimental Trypanosoma cruzi infection. Wistar male rats were infected with the Y strain of T. cruzi. One group of animals was also treated with the NO synthase inhibitor N-nitro-l-arginine. A group of uninfected animals was the control. At the 18th day of infection the animals were sacrificed. Quantification of neurons in the colon and heart and tissue parasitism in the heart was performed. Serum concentration of nitrate was measured and a histochemical technique for assessing NADPH-diaphorase activity in the colon was also performed. The infected animals presented a statistically significant decrease in the number of peripheral neurons in the colon and heart and a 2-fold increase in serum NO(3) concentration compared with controls. The animals treated with N-nitro-l-arginine showed almost an absence of NO(3) concentration in the serum and did not show loss of neurons compared with controls. These treated animals displayed a 15-fold increase in tissue parasitism compared with nontreated infected animals. The NADPH-diaphorase activity was much more intense in the muscle layers of the colon of the infected animals than in those of the controls. Taken together, these data suggest that NO is involved in the peripheral denervation observed in the acute phase of experimental T. cruzi infection.

Acute Disease↗

PubMed1999

Intrinsic myenteric denervation: a new model to increase the intestinal absorptive surface in short-bowel syndrome.

INTRODUCTION: Short-bowel syndrome (SBS) is caused by resection of massive portions of the small intestine and is characterized by symptoms related to malabsorption, of which severe weight loss is the most apparent. Surgical treatments for SBS are not yet satisfactory. In rats, the myenteric denervation by benzalkonium chloride (BAC) leads to development of megaileum with visceral dilatation and mucosal hyperplasia and increases the intestinal transit time. Such operation in the remaining intestinal segment after massive small bowel resection could increase the duration of contact between luminal nutrients and ileal mucosal epithelium, and furthermore, it could increase the superficial area of the mucosa. Thus, our aim in this study was to evaluate the epithelial morphology and body weight changes of animals after intrinsic ileal denervation associated with extensive small intestine resection. MATERIAL AND METHODS: Wistar rats were submitted to resection of 80% of small intestinal length (Group R). Another group (B) of animals also received topical serosal application of BAC 0.3%. Control animals were submitted to simulated surgery (Group C). Animals were weighed weekly and sacrificed after 90 days. Intestinal walls were collected for histological procedure and morphometry. RESULTS: At the end of the experimental period all groups showed weight increase, which was reduced in the R group (P < 0.01). Interestingly, the denervated Group B showed a marked increase in weight, similar to the control animals. Morphometric analysis of the mucosal layer area showed a major increase in mucosal surface area, mainly in Group B. CONCLUSIONS: Our results showed that the ileal intrinsic denervation associated with massive intestinal resection induced an increase in the superficial absorptive area and was able to improve the postsurgical conditions for the animals, with accentuated weight increase. This procedure may be a useful model for further studies related to the role of the enteric nervous system on intestinal adaptations after extensive resections and may provide a new approach for the surgical treatment of short-bowel syndrome.

Animals↗

PubMed1999

Origins and morphogenesis of colorectal neoplasms.

Gastrointestinal stem cells are considered pivotal in colonic carcinogenesis. There is evidence to suggest that early microadenomas in the colon are polyclonal in origin. Adenomas, once initiated, enlarge by the process of crypt fission. It is also the main mechanism by which neoplastic clones spread through the colorectal epithelium. Both concepts are important for our understanding of the early events in colonic carcinogenesis.

Animals↗

PubMed1997

The relationship between myenteric neuronal denervation, smooth muscle thickening and epithelial cell proliferation in the rat colon.

The effects of myenteric neuronal denervation on smooth muscle thickening and epithelial cell proliferation were studied in the descending colon of rats treated by serosal application of 2 mM benzalkonium chloride (BAC) for 30 min. Control animals were treated with saline (0.9% NaCl). The animals were divided into six groups of 13 animals each and killed 10, 45 and 120 days after BAC treatment. A significant reduction in neuron number was observed in the myenteric plexus of animals treated with BAC, as well as smooth muscle thickening and an increase in crypt cell population, crypt cell production per crypt and a decrease in cell cycle time. These findings permit us to conclude that a relationship may exist between the increase of epithelial cell proliferation, smooth muscle thickening and myenteric neuron denervation in the descending colon caused by BAC, the latter probably playing an important role in the integration of the other two.

Animals↗

PubMed1996

The relationship between megacolon and carcinoma of the colon: an experimental approach.

'Carcinoma of the colon does not occur in cases of megacolon' is an axiom held by Brazilian physicians working in endemic areas for Chagas' disease. The objective of the present study was to test this axiom experimentally by submitting rats with experimental megacolon to a carcinogen which causes carcinoma of the colon. Eighty young male Wistar rats received serosal application of either saline (0.9% NaCl) or 2 mM benzalkonium chloride (BAC) to the distal colon. Ten months later randomly chosen saline and BAC rats were injected weekly with dimethylhydrazine (DMH) for 20 weeks. Non-DMH-treated rats from both original groups were maintained, for a total of four experimental groups. Three months after the injections all surviving rats were killed. At autopsy the presence of absence of carcinomas along the colon was recorded. The induction of megacolon was evaluated by morphometry of the wall from the distal colon and myenteric denervation was assessed by neuron counts. An increase of at least 2-fold in distal colon wall thickness confirmed the induction of megacolon in BAC-treated rats. Neuronal counts from BAC and control rats not treated with DMH showed an average denervation of 63%. The number of distal colon carcinomas in BAC+DMH-treated rats was significantly lower than that in DMH-treated rats. These findings appear to contradict the traditional concept of carcinogenesis of the colon. The clinical axiom was reproduced experimentally.

1,2-Dimethylhydrazine↗

PubMed1995

Mouse ear spleen grafts: a model for intrasplenic immunization with minute amounts of antigen.

The production of monoclonal antibodies to protein antigens which can only be obtained in tiny amounts has been a major task, since classical in vivo immunization procedures are not always efficient. In order to circumvent this problem, two methods have been developed: (1) in vitro immunization, in which the immunogen is presented directly to spleen cell cultures; (2) intrasplenic immunization, a technique in which the immunogen is deposited in the spleen tissue. The latter approach requires less laboratory work and the risk of contamination, often a problem with in vitro cultures (Nilsson and Larsson, Immunol. Today (1990) 11, 10), is greatly reduced. Here, we describe a novel method of grafting neonatal spleens in the pinna of the mouse ear. Histological and functional studies show that these spleen grafts have white and red pulp and contain normal percentages of functional T and B cells. The results indicate that this procedure is extremely efficient in priming mice for a secondary humoral immune response, since very small amounts of soluble antigen (ovalbumin) were required. The data are discussed in terms of the advantages of this new technique over current procedures for intrasplenic immunization.

Animals↗

PubMed1995

Experimental megaileum.

Typical megaileum occurred in young male Wistar rats three months after ileum myenteric plexus denervation. An average of 58.4% denervation of the Auerbach plexus was obtained by serosal application of benzalkonium chloride (0.2% v/v). Denervation was assessed by ganglion cell counts in an 8 nm ring-shaped histological sectfrom the midportion of the treated segment. A morphometric study showed that the increased thickness of the megaileum wall was due to muscle hypertrophy and mucosal hyperplasia. The potential usefulness of this model of megaileum is emphasized.

Animals↗