Reproductive evaluation of aqueous crude extract of Achillea millefolium L. (Asteraceae) in Wistar rats

The present study was conducted to evaluate the toxicity of the exposure to the aqueous extract from leaves (AE) of Achillea millefolium L. on reproductive endpoints in Wistar rats. Adult male rats were treated daily with yarrow extract (0.3, 0.6 and 1.2 g/kg/day) during 90 days by oral gavage. Endpoints including reproductive organ weights, sperm and spermatid numbers as well as sperm morphology were evaluated. No clinical signs of toxicity were detected over the treatment period, and body weight gain was similar in all groups. A significant increase in the percentage of abnormal sperm in the group treated with the highest dose of yarrow extract was detected with no other important changes in the other reproductive endpoints studied in the male rats. Furthermore, a possible estrogenic/antiestrogenic activity of the yarrow extract screened after a 3-day treatment of immature female rats which did not show any uterotrophic effects.     

Embryotoxicity in vitro with extract of Indigofera suffruticosa leaves

Aqueous extract of leaves of Indigofera suffruticosa (AELIs) were studied for adverse effects in preimplantation mouse embryos. Two-cell mouse embryos were cultured for 94 h in human tubal fluid medium (HTF), and AELIs at a concentration of 5 or 10 mg/ml. On Day 4 of culture, morulae and blastocysts were collected for morphological analysis of blastomeres. We found that embryos exposed to the higher concentration of AELIs (10 mg/ml) did not develop and all embryos persisted at the two-cell stage. Those embryos exposed to the lower concentration (5 mg/ml) showed development until morula, blastocyst and hatched blastocyst stages that were similar to the controls. These results suggest that use of AELIs may be hazardous to humans who make use of it in folk medicine.     

Comparison of the effectiveness of bacterial culture, 16S rDNA directed polymerase chain reaction, and checkerboard DNA-dNA hybridization for detection of Fusobacterium nucleatum in endodontic infections

Fusobacterium nucleatum is a Gram-negative, non-spore-forming, nonmotile, obligatory anaerobic rod that is normally isolated from the oral cavity. Epidemiological studies have shown that this species is one of the most prevalent in primary root canal infections. The purpose of this study was to compare the effectiveness of bacteriological culture, 16S rDNA directed polymerase chain reaction and checkerboard DNA-DNA hybridization for detection of F. nucleatum strains in infected teeth associated with periradicular lesions. Thirteen single-root teeth from adult patients, all having carious lesions, necrotic pulps, and radiographic evidence of periradicular bone loss were included in this study. Combining all methods, the results indicated that F. nucleatum was present in approximately 31% (4 of 13) of the specimens. Incidence of F. nucleatum in root canal infections, as evaluated in this study by polymerase chain reaction, culture, and DNA-DNA hybridization, was 15.4%, 15.4%, and 10.0%, respectively. Our data demonstrated that no method used herein could be considered superior for detecting F. nucleatum directly from clinical samples. However, the small number of samples examined and the low prevalence that was observed should be considered.     

Osteosarcoma of the temporomandibular joint: report of 2 cases

The aim of this article is to report 2 cases of osteosarcoma of the mandibular condyle, a rare pathological condition, and to emphasize and discuss the usefulness of different imaging modalities in the diagnosis and evaluation of osteosarcoma of the temporomandibular joint. In our assessment of the different imaging modalities, we found that 2-dimensional computed tomograms provide excellent detection of tumor calcification, cortical involvement, and in most instances, soft tissue and intramedullary extension, whereas 3-dimensional computed tomography vascular protocol can help to define the extension of the lesion, improving the visualization of the lesion's relationship to the adjacent anatomical structures. Magnetic resonance imaging is more effective in demonstrating the intramedullary and extraosseous tumor components on T2 weighted images. Because metastasis from body tumors to the maxillofacial region occurs occasionally, it is useful to examine the oral cavity when symptoms first appear and devote special attention to the subtle changes that may indicate early metastatic involvement.     

Analysis by mathematical model of haemodynamic data in the failing Fontan circulation

Several late complications jeopardize the clinical performance of recipients of the Fontan operation. The underlying causes have been referred to disturbed flow dynamics in the cavopulmonary connections. Presumably, the large pressure drops occurring in the inferior and superior connections play a pivotal role in the pressure level of the entire circulation, especially in the venous. To address this issue, we retrospectively reviewed catheterization data of six patients with failing Fontan circulation and compared them with those of six patients with functioning Fontan circulation. The impact on the systemic and pulmonary pressure of the increase in the cavopulmonary connection resistances was studied through a steady-state mathematical model of the univentricular closed-loop circulation. In the patients with failing Fontan, pressure in the venae cavae was found to be significantly higher, especially at the inferior cava (19.3 +/- 2.2 versus 12.5 +/- 2.3 mmHg) with the pressure drop at the inferior cavopulmonary connection significantly increased (4.7 +/- 3.1 versus 0.33 +/- 0.82 mmHg). The proposed mathematical model permits us to clearly relate the pressure increase in the venae cavae to an increased resistance in the cavopulmonary connections. Therefore, the present analysis confirms that, to avoid possible congestion of venous circulation, the definitive palliation of univentricular heart should not cause pressure drops at the cavopulmonary connections.     

The effect of oestrogen and testosterone on the urethral seam of the developing male mouse genital tubercle

OBJECTIVES: To describe the effects of exogenous oestrogens and androgens on urethral formation in the mouse, as the development of the mouse and human urethra have significant similarities, and understanding normal male urethral development may help to identify the causes of abnormal development, e.g. hypospadias. MATERIALS AND METHODS: Timed-pregnant C57/6 mice were exposed to synthetic oestrogens and androgens. The morphology of the genital tubercles was examined histologically and with three-dimensional computer reconstruction. Specific attention was focused on the developing urethral seam. RESULTS: Microscopic serial analysis confirmed the presence of an arrest in seam formation in about half of oestrogen-treated male fetuses. In contrast, there was acceleration of urethral fold fusion and a longer urethral tube in those treated with androgens. Oestrogen-treated fetuses had a thin periurethral spongiosa, in contrast to androgen-treated fetuses which developed a thicker periurethral spongiosa. The effect of oestrogens on seam area formation did not depend on the dose, but in contrast, in the androgen-treated fetuses it was. CONCLUSION: Oestrogens and androgens have a direct effect on the fusion of the urethral fold that leads to seam formation. Normal urethral development depends on the delicate balance of these complementary hormones.     

Antinociceptive and antiedematogenic properties and acute toxicity of Tabebuia avellanedae Lor. ex Griseb. inner bark aqueous extract

Background

The search for an optimal experimental model in pharmacology is recently focused on (mini)pigs as they seem not only to be an alternative source of cells and tissues for xenotherapy but also an alternative species for studies on drug metabolism in man due to similarities between (mini) pig and human drug metabolizing systems. The purpose of this work is to characterize minipig liver microsomal cytochromes P450 (CYPs) by comparing their N-terminal sequences with corresponding human orthologs.

Results

The microsomal CYPs exhibit similar activities to their human orthologous enzymes (CYP3A4, nifedipine oxidation; 2A6, coumarin 7-hydroxylation; 2D6, bufuralol 1'-hydroxylation; 2E1, p-nitrophenol hydroxylation; and 2C9, tolbutamide hydroxylation). Specific minipig CYP (2A, 2C and 3A) enzymes were partially purified and proteins identified by immunostaining (using antibodies against the respective human CYPs) were used for N-terminal amino acid sequencing. From comparisons, it can be concluded that the sequence of the first 20 amino acids at the N-terminus of minipig CYP2A is highly similar to human CYP2A6 (70% identity). The N-terminal sequence of CYP2C shared about 50% similarity with human 2C9. The results on the minipig liver microsomal CYP3A yielded identical data with those obtained for amino acid sequences of the pig CYP3A29 showing 60% identity with human CYP3A4.

Conclusions

Thus, our results further support the view that minipigs may serve as model animals in pharmacological/toxicological studies with substrates of human CYP enzymes, namely, of the CYP3A and CYP2A forms.     

Arterial baroreflex influence on heart rate variability: A mathematical model-based analysis

The influence of the arterial baroreflex on the heart rate variability is analysed by using a mathematical model of heart rate baroreceptor control. The basic mechanisms of the model, sufficient to elicit heart rate variability include: systemic circulation, a non-pulsatile cardiac pump and nonlinear negative feedback simulating arterial baroreflex closed-loop control of the heart rate (−3bpm/mmHg as maximum reflex sensitivity). The latter reproduces, through two distinct delayed branches (0.8 and 2.8 s), the short-term autonomic control effected respectively by sympathetic and parasympathetic divisions on the sinus node. By means of this model, two distinct self-sustained oscillatory components with incommensurate frequencies (0.1 and 0.26 Hz) are reproduced. Frequencies of these two oscillatory components closely agree with the main heart rate rhythms in humans (0.09±0.01 Hz and 0.26±0.01 Hz). When sympathetic-mediated regulation prevails over parasympathetic activity, simulated heart rate oscillation is characterised by a low frequency (∼0.1 Hz). On the other hand, a high-frequency oscillatory component (∼0.26 Hz) appears when enhanced vagal activation or partial inhibition of the sympathetic control is simulated. When both autonomic divisions are operative, both low- and high-frequency components are present and the heart rate oscillates quasi-periodically. This variability in heart rate at different frequencies is reproduced without including outside perturbations and is due to the nonlinear delayed structure of the closed-loop control. Bifurcation theory of nonlinear system is used to explain the high sensitivity of the heart rate oscillatory pattern to model parameter changes.     

Treatment of liver metastases with moderate peritoneal carcinomatosis by hepatectomy and cytoreductive surgery followed by immediate post-operative intraperitoneal chemotherapy: feasibility and preliminary results

BACKGROUND/AIMS: Peritoneal carcinomatosis (PC) discovered during hepatectomy is usually a contraindication to resection. A potentially efficient treatment of PC is the resection of the macroscopic disease and the treatment of the residual microscopic disease with immediate post-operative intraperitoneal chemotherapy (IPIC) (before the entrapment of cancer cells inside the fibrin deposit which rapidly cover the injured tissues). Feasibility and survival results of this treatment, combined with major hepatectomy, have never been evaluated. The purpose of this study is to report tolerance and preliminary results in patients with liver metastases synchronous to moderate PC, treated with hepatectomy, complete cytoreductive surgery, and IPIC. METHODOLOGY: Twelve patients with liver metastases and moderate PC from miscellaneous origins, underwent: 1) hepatectomy (9 of them were major hepatectomies); 2) complete cytoreductive surgery of the PC resecting between 20 and 150 nodules; and, 3) IPIC, for 5 days, according to histology. RESULTS: There was no mortality. Morbidity was mainly due to four transient biliary leakages (33%) and there was no systemic complication due to the chemotherapy. After a median follow-up of 14.4 months, there was no detectable recurrence of the PC. Preliminary results concerning survival are promising with 7 patients without recurrent disease. CONCLUSIONS: When a minimal or moderate PC is discovered during laparotomy for liver resection of metastases, the combination of hepatectomy with complete cytoreductive surgery of the peritoneal disease, followed with IPIC is logical and feasible. This aggressive treatment is well tolerated although the frequency of biliary leakage seems to be higher than that after standard hepatectomy. No recurrence of the peritoneal disease was detected and survival results are very promising.