Dynamics of fibrosis production and resorption in intestinal schistosomiasis of mice

A histological, morphometric and immunocytochemical study of schistosomal periovular granulomas in the liver and intestines of mice revealed that intestinal granulomas are smaller and contain less collagen than those in the liver. After curative treatment intestinal granulomas undergo a relatively more rapid resorption, although the general pattern of collagen degradation apparently does not differ from that observed in the liver. Tendency to form scattered, usually isolated granulomas that are only mildly fibrogenic, coupled with a well-balanced process of resorption appear as the explanation why intestinal fibrosis is not an outstanding feature of schistosomiasis as it is in the liver.

Fibrogenesis and collagen resorption in the heart and skeletal muscle of Calomys callosus experimentally infected with Trypanosoma cruzi: immunohistochemical identification of extracellular matrix components

Intense inflammatory lesions and early development of interstitial fibrosis of the myocardium and skeletal muscle with spontaneous regression, have been described in Calomys callosus infected with Trypanosoma cruzi. The genetic types of collagen present in this model were investigated through immunohistochemistry using specific antibodies, combined with histopathology and Picro-Sirius staining of collagen. Thirty-five calomys were infected with the Colombian strain of T. cruzi and sacrificed at 24, 30, 40, 60 and 90 days post-infection. Inflammatory lesions and fibrogenesis were prominent at the early phase of infection and significantly decreased during late infection. Immunoisotyping of the matrix components was performed by indirect immunofluorescence on 5 µm thick cryostat sections using specific antibodies against laminin, fibronectin and isotypes I, III and IV of collagen. In the early phase, positive deposits of all the matrix components were present, with predominance of fibronectin, laminin and collagens types I and III in the myocardium and of types III and IV in the skeletal muscles. From the 40th day, type IV collagen predominates in the heart. At the late phase of infection (60th to 90th day), a clear fragmentation and decrease of all the matrix components were detected. Findings of the present study indicate that a modulation of the inflammatory process occurs in the model of C. callosus, leading to spontaneous regression of fibrosis independent of the genetic types of collagen involved in this process.

Low-dose doxycycline prevents inflammatory bone resorption in rats

Matrix metalloproteinases (MMP) are considered to be key initiators of collagen degradation, thus contributing to bone resorption in inflammatory diseases. We determined whether subantimicrobial doses of doxycycline (DX) (<=10 mg kg-1 day-1), a known MMP inhibitor, could inhibit bone resorption in an experimental periodontitis model. Thirty male Wistar rats (180-200 g) were subjected to placement of a nylon thread ligature around the maxillary molars and sacrificed after 7 days. Alveolar bone loss (ABL) was measured macroscopically in one hemiarcade and the contralateral hemiarcade was processed for histopathologic analysis. Groups of six animals each were treated with DX (2.5, 5 or 10 mg kg-1 day-1, sc, 7 days) and compared to nontreated (NT) rats. NT rats displayed significant ABL, severe mononuclear cell influx and increase in osteoclast numbers, which were significantly reduced by 5 or 10 mg kg-1 day-1 DX. These data show that DX inhibits inflammatory bone resorption in a manner that is independent of its antimicrobial properties.

Occurrence and risk factors associated with infection by Toxoplasma gondii in goats in the State of Alagoas, Brazil

INTRODUCTION: Goats are considered very susceptible to infection by Toxoplasma gondii and when this occurs during pregnancy, it may cause fetal death with subsequent fetal resorption, abortion, mummification, stillborn or the birth of weak goats. The objective of this work was to determine the occurrence of and identify risk factors for T. gondii infection in goats in different mesoregions in the State of Alagoas. METHODS: The research was conducted on 24 goat breeding farms in 10 municipalities. A total of 454 blood samples were examined for anti-T. gondii antibodies by indirect immunofluorescence antibody test. To evaluate the risk factors of toxoplasmosis in goats, questionnaires were applied analyzing the farm's production system and nutritional, reproductive and sanitary management. RESULTS: Disease occurrence was 39% with 95.8% of farms presenting seropositive animals. Significant associations were observed for mesoregion (OR = 0.23; 95%CI = 0.09 - 0.57), age (OR = 0.36; 95%CI = 0.20 - 0.64), semi-intensive herd management (OR = 8.70; 95%CI = 1.87 - 40.43), access of cats to water provided for goats (OR = 3.38; 95%CI = 1.89-6.02) and cats feeding on placental remnants (OR = 2.73; 95%CI = 1.38 - 5.40). CONCLUSIONS: Toxoplasma gondii infection is disseminated in the State of Alagoas and the adoption of a program that monitors infection foci is required to reduce the risk factors identified in the present study.

ABORTIFACIENT EFFECTS OF Ananas ananassoides BAK. (Ananai) IN RATS

The tea made from the infrutescense (corresponding to the edible part plus its cover) of ananai (Ananas ananassoidesBAK.) was administered to pregnant rats, during the period of embryos implantation (5th - 6th day through pregnancy). The animals were slaughtered on the 14th - 15th day through the pregnancy and average rates of implantation and resorption were stimated.

Influence of Spironolactone on Matrix Metalloproteinase-2 in Acute Decompensated Heart Failure

Background: Matrix metalloproteinases (MMPs) are a family of enzymes important for the resorption of extracellular matrices, control of vascular remodeling and repair. Increased activity of MMP2 has been demonstrated in heart failure, and in acutely decompensated heart failure (ADHF) a decrease in circulating MMPs has been demonstrated along with successful treatment. Objective: Our aim was to test the influence of spironolactone in MMP2 levels. Methods: Secondary analysis of a prospective, interventional study including 100 patients with ADHF. Fifty patients were non-randomly assigned to spironolactone (100 mg/day) plus standard ADHF therapy (spironolactone group) or standard ADHF therapy alone (control group). Results: Spironolactone group patients were younger and had lower creatinine and urea levels (all p < 0.05). Baseline MMP2, NT-pro BNP and weight did not differ between spironolactone and control groups. A trend towards a more pronounced decrease in MMP2 from baseline to day 3 was observed in the spironolactone group (-21 [-50 to 19] vs 1.5 [-26 to 38] ng/mL, p = 0.06). NT-pro BNP and weight also had a greater decrease in the spironolactone group. The proportion of patients with a decrease in MMP2 levels from baseline to day 3 was also likely to be greater in the spironolactone group (50% vs 66.7%), but without statistical significance. Correlations between MMP2, NT-pro BNP and weight variation were not statistically significant. Conclusion: MMP2 levels are increased in ADHF. Patients treated with spironolactone may have a greater reduction in MMP2 levels.

Action of colchicine on hepatic schistosomal granuloma

Amorphous material and altered collagen fragments within dilated secretory vesicles and cisternae of fibroblast cytoplasm were the main ultrastructural changes seen in hepatic periovular granulomas formed in mice infected with Schistosoma mansoni and treated with colchicine. Despite promoting ultrastructural changes in the fibroblasts found in hepatic periovular granulomas, colchicine administration to infected mice did not significantly change the light microscopic appearance of the hepatic schistosomal lesions, did not diminish the amount of total hepatic collagen, and did not change the collagen isotypes in the granulomas, as observed after a comparative study with non-colchicine treated infected control mice. When administered to mice two weeks after curative treatment of schistosomiasis with praziquantel, colchicine did not seem to increase extracellular collagen degradation or to induce a more rapid resorption of hepatic periovular granulomas, although still promoting ultrastructura alterations in fibroblasts.

Host nutritional status as a contributory factor to the remodeling of schistosomal hepatic fibrosis

Weaning Swiss mice were percutaneously infected with 30 cercariae of Schistosoma mansoni and submitted to a shifting either from a deficient to a balanced diet or vice-versa, for 24 weeks. The nutritional status was weekly evaluated by measurements of growth curves and food intake. Hepatic fibrosis and periovular granulomas were studied by histological, morphometric and biochemical methods. All mice fed on a deficient diet failed to develop periportal "pipestem" fibrosis after chronic infection. An unexpected finding was the absence of pipestem fibrosis in mice on normal diet, probably related to the sample size. The lower values for nutritional parameters were mainly due to the deficient diet, rather than to infection. Liver/body weight ratio was higher in "early undernutrition" group, after shifting to the balanced diet. Volume density and numerical density of egg granulomas reached lowest values in undernourished animals. The amount of collagen was reduced in undernourished mice, attaining higher concentrations in well-fed controls and in "late undernutrition" (balanced diet shifted to a deficient one), where collagen deposition appeared increased in granulomas. That finding suggested interference with collagen degradation and resorption in "late" undernourished animals. Thus, host nutritional status plays a role in connective tissue changes of hepatic schistosomiasis in mice.

Mycobacterium leprae downregulates the expression of PHEX in Schwann cells and osteoblasts

Neuropathy and bone deformities, lifelong sequelae of leprosy that persist after treatment, result in significant impairment to patients and compromise their social rehabilitation. Phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) is a Zn-metalloendopeptidase, which is abundantly expressed in osteoblasts and many other cell types, such as Schwann cells, and has been implicated in phosphate metabolism and X-linked rickets. Here, we demonstrate that Mycobacterium leprae stimulation downregulates PHEX transcription and protein expression in a human schwannoma cell line (ST88-14) and human osteoblast lineage. Modulation of PHEX expression was observed to a lesser extent in cells stimulated with other species of mycobacteria, but was not observed in cultures treated with latex beads or with the facultative intracellular bacterium Salmonella typhimurium. Direct downregulation of PHEX by M. leprae could be involved in the bone resorption observed in leprosy patients. This is the first report to describe PHEX modulation by an infectious agent.

Retrospective study of sonographic findings in bone involvement associated with rotator cuff calcific tendinopathy: preliminary results of a case series

Abstract Objective: The present study was aimed at investigating bone involvement secondary to rotator cuff calcific tendonitis at ultrasonography. Materials and Methods: Retrospective study of a case series. The authors reviewed shoulder ultrasonography reports of 141 patients diagnosed with rotator cuff calcific tendonitis, collected from the computer-based data records of their institution over a four-year period. Imaging findings were retrospectively and consensually analyzed by two experienced musculoskeletal radiologists looking for bone involvement associated with calcific tendonitis. Only the cases confirmed by computed tomography were considered for descriptive analysis. Results: Sonographic findings of calcific tendinopathy with bone involvement were observed in 7/141 (~ 5%) patients (mean age, 50.9 years; age range, 42-58 years; 42% female). Cortical bone erosion adjacent to tendon calcification was the most common finding, observed in 7/7 cases. Signs of intraosseous migration were found in 3/7 cases, and subcortical cysts in 2/7 cases. The findings were confirmed by computed tomography. Calcifications associated with bone abnormalities showed no acoustic shadowing at ultrasonography, favoring the hypothesis of resorption phase of the disease. Conclusion: Preliminary results of the present study suggest that ultrasonography can identify bone abnormalities secondary to rotator cuff calcific tendinopathy, particularly the presence of cortical bone erosion.

Alendronato de sódio: metodologias para análise quantitativa

This paper presents a review of some published proposals for the analysis of sodium alendronate. The drug is an aminobisphosphonate compound used to inhibit the osteoclastic resorption of bone, and different methods were developed for its quantitative determination. These methodologies employed reversed-phase or ion-exchange HPLC analysis, both associated with different detectors: UV and fluorescence detection after derivatization of the drug, conductivity and refractive index detectors, as well as the indirect UV detection. Titrimetry and spectrophotometry (with previous complexation of the drug), which are simpler procedures, were also described, but they showed poor specificity when compared to liquid chromatography.

Bone changes caused by experimental Solanum malacoxylon poisoning in rabbits

The aim of this study was to describe the bone changes observed after a daily oral administration of the calcinogenic plant Solanum malacoxylon (syn. S. glaucophyllum) (Sm) during 9 days. The Sm-poisoned rabbits had an increase of bone resorption in the endosteal surface of the cortical zone and also in the surface covered by osteoblasts of the primary and secondary spongiosa of the trabecular bone compartment. Moreover, the epiphyseal growth plates in long bones appeared narrower than in the control rabbits, with reduction of the proliferative and hyperthrophic chondrocyte zones. The electron microscopic study revealed a significant decrease of proteoglycans in the hyperthrophic chondrocyte zone evidenced by a significant reduction of rutenium red positive granules in the poisoned rabbit. Altogether, these data suggest that cell differentiation may play a pivotal role in the pathogenesis of Sm-induced bone lesions.

Histopathological and histomicrobiological study of root canal therapy medication, comparison of calcium hydroxide versus gutta-percha with zinc oxide/eugenol in the teeth of dogs

The presence of microorganisms in dental structures with experimentally induced necrosis was evaluated. The materials were tested to evaluate their antimicrobial activity and tissue repair efficacy. Four dogs were used in this experiment, with a total of 64 roots of premolar teeth, divided into three groups. The root canals of Group I were filled with gutta-percha and zinc oxide/eugenol cement; Group II were filled with calcium hydroxide, and Group III were not filled. All animals were clinically and radiographically examined 15 days after surgery andthen again every subsequent 15 days until 120 days, when the teeth were extracted en bloc.Histopathological analysis showed inflammatory infiltration, cement and bone resorption andnecrotic tissue in the apical delta in different proportions. Histomicrobiological analysis showedthe presence of microorganisms inside the teeth structures, with different concentrationsaccording to the treatment used. There was statistical significance between the groups(p>0.05). Gutta-percha with zinc oxide/eugenol demonstrated good antimicrobial activity;calcium hydroxide was not efficient. The conclusion of this study is that gutta-percha withzinc oxide/eugenol is the better protocol for filling root canals in dogs.

Study of the embryofeto-toxicity of Crown-of-Thorns (Euphorbia milii) latex, a natural molluscicide

The crude latex of Crown-of-Thorns (Euphorbia milii var. hislopii) is a potent plant molluscicide and a promising alternative to the synthetic molluscicides used in schistosomiasis control. The present study was undertaken to investigate the embryofeto-toxic potential of E. milii latex. The study is part of a comprehensive safety evaluation of this plant molluscicide. Lyophilized latex (0, 125, 250 and 500 mg/kg body weight) in corn oil was given by gavage to Wistar rats (N = 100) from days 6 to 15 of pregnancy and cesarean sections were performed on day 21 of pregnancy. The numbers of implantation sites, living and dead fetuses, resorptions and corpora lutea were recorded. Fetuses were weighed, examined for external malformations, and fixed for visceral examination, or cleared and stained with Alizarin red S for skeleton evaluation. A reduction of body weight minus uterine weight at term indicated that E. milii latex was maternally toxic over the dose range tested. No latex-induced embryolethality was noted at the lowest dose (125 mg/kg) but the resorption rate was markedly increased at 250 mg/kg (62.5%) and 500 mg/kg (93.4%). A higher frequency of fetuses showing signs of delayed ossification (control: 17.4%; 125 mg/kg: 27.4% and 250 mg/kg: 62.8%; P<0.05 vs control) indicated that fetal growth was retarded at doses ³ 125 mg latex/kg body weight. No increase in the proportion of fetuses with skeletal anomalies was observed at the lowest dose but the incidence of minor skeletal malformations was higher at 250 mg/kg body weight (control: 13.7%; 125 mg/kg: 14.8%; 250 mg/kg: 45.7%; P<0.05 vs control). Since a higher frequency of minor malformations was noted only at very high doses of latex which are embryolethal and maternally toxic, it is reasonable to conclude that this plant molluscicide poses no teratogenic hazard or, at least, that this possibility is of a considerably low order of magnitude

Study of the effects of ß-myrcene on rat fertility and general reproductive performance

ß-Myrcene (MYR) is a monoterpene found in the oils of a variety of aromatic plants including lemongrass, verbena, hop, bay, and others. MYR and essential oils containing this terpenoid compound are used in cosmetics, household products, and as flavoring food additives. This study was undertaken to investigate the effects of MYR on fertility and general reproductive performance in the rat. MYR (0, 100, 300 and 500 mg/kg) in peanut oil was given by gavage to male Wistar rats (15 per dose group) for 91 days prior to mating and during the mating period, as well as to females (45 per dose group) continuously for 21 days before mating, during mating and pregnancy, and throughout the period of lactation up to postnatal day 21. On day 21 of pregnancy one-third of the females of each group were submitted to cesarean section. Resorption, implantation, as well as dead and live fetuses were counted. All fetuses were examined for external malformations, weighed, and cleared and stained with Alizarin Red S for skeleton evaluation. The remaining dams were allowed to give birth to their offspring. The progeny was examined at birth and subsequently up to postnatal day 21. Mortality, weight gain and physical signs of postnatal development were evaluated. Except for an increase in liver and kidney weights, no other sign of toxicity was noted in male and female rats exposed to MYR. MYR did not affect the mating index (proportion of females impregnated by males) or the pregnancy index (ratio of pregnant to sperm-positive females). No sign of maternal toxicity and no increase in externally visible malformations were observed at any dose level. Only at the highest dose tested (500 mg/kg) did MYR induce an increase in the resorption rate and a higher frequency of fetal skeleton anomalies. No adverse effect of MYR on postnatal weight gain was noted but days of appearance of primary coat, incisor eruption and eye opening were slightly delayed in the exposed offspring. On the basis of the data presented in this paper the no-observed-adverse-effect level (NOAEL) for toxic effects on fertility and general reproductive performance can be set at 300 mg of ß-myrcene/kg body weight by the oral route.