Antiplatelet and antithrombotic activities of essential oil from wild Ocotea quixos (Lam.) Kosterm. (Lauraceae) calices from Amazonian Ecuador.

Ocotea quixos essential oil was shown to possess significant inhibitory activity of platelet aggregation and clot retraction in rodent plasma. This study is aimed at fully characterizing the antiplatelet activity of the whole essential oil and its main components trans-cinnamaldehyde and methyl cinnamate also in human plasma, at investigating the mechanism underlying such activity and at evaluating the potential antithrombotic activity of subacute treatment of mice with Ocotea essential oil. In vitro Ocotea essential oil and trans-cinnamaldehyde inhibited arachidonic acid-, U46619-, ADP-, phorbol12-myristate13-alcetate-, collagen-induced platelet aggregation and thrombin-induced clot retraction in human and rodent plasma; Ocotea oil and trans-cinnamaldehyde competitively antagonized contractions induced by thromboxane A2 receptor agonist U46619 in rat isolated aortic ring (K(B) = 18 and 3.2 microg ml(-1), respectively). In vivo Ocotea oil, orally administered in a subacute treatment (30-100 mg kg(-1) day(-1) for 5 days) to mice, prevented acute thrombosis induced by collagen-epinephrine intravenous injection. This antithrombotic activity was not accompanied by pro-haemorragic side effect, as detected by the inactivity in bleeding test, thus showing a favourable safety profile compared to the conventional antiplatelet agent, acetylsalicylic acid. Present findings indicate that Ocotea essential oil possesses potent and safe antithrombotic activity attributable to its antiplatelet and vasorelaxant effects. The main constituent trans-cinnamaldehyde seems to be the primary responsible for this activity through a putative mechanism involving the inhibition of thromboxane A2 receptors.     

Symptom profile of DSM-IV major and minor depressive disorders in first-ever stroke patients.

OBJECTIVE: Depressive disorders are very common in stroke patients. However, vegetative and cognitive symptoms primarily derived from brain damage could hypothetically be indistinguishable from those directly derived from neuropsychiatric disorders, and this could invalidate the diagnostic assessment. Thus, authors aimed to detect the frequency of clinically-rated DSM-IV depressive symptoms and the diagnostic validity of depressive disorders in stroke patients suffering from major depressive disorder (MDD), minor depressive disorder (MIND), and those free of any neuropsychiatric disorders (NODEP). METHODS: First-ever stroke patients (N=200) were approached within 3 months of the acute stroke and were interviewed with the SCID-P and administered the Hamilton Rating Scale for Depression (Ham-D), the Beck Depression Inventory (BDI), the Barthel Index, and the Mini-Mental State Exam. RESULTS: Fifty patients (25%) had MDD, 62 (31%) had MIND, and 88 (44%) had NODEP. Global cognitive level, functional impairment, total scores, and psychic and somatic subscores of the Ham-D and the BDI were different among the three groups. The only symptom that did not differ among patients with MDD, MIND, and NODEP was Feelings of Guilt; all the other eight DSM-IV symptoms were significantly different. In particular, the frequency of Depressed Mood, Diminished Interest or Pleasure, Fatigue or Loss of Energy, Insomnia, and Psychomotor Agitation/Retardation was higher in MIND patients than in NODEP patients. CONCLUSIONS: During the diagnostic procedure for depressive disorders in stroke patients, clinicians should consider equally important vegetative, cognitive, and psychological depressive symptoms, despite their nature.     

Temporal lobe dual pathology in malignant migrating partial seizures in infancy.

A child had the characteristic clinical and EEG pattern of migrating partial seizures in infancy with left temporal lobe atrophy, hippocampal sclerosis and cortical-subcortical blurring.Seizures were drug-resistant, with recurring episodes of status epilepticus. The child developed microcephaly with arrest of psychomotor development. Focal brain lesions, in the context of migrating partial seizures, have not been previously reported.[Published with video sequences].     

Endodontic surgery using 2 different magnification devices: preliminary results of a randomized controlled study.

PURPOSE: The introduction of microsurgical instruments and magnification devices has brought advantages in root-end management and the application of root-end filling materials. The main purpose of this prospective clinical study was to monitor the outcome of ultrasonic root-end preparation using magnification loupes or an endoscope. Tooth location and the presence of post restoration were also examined as potentially affecting the outcome. MATERIALS AND METHODS: Teeth treated surgically showed a periradicular lesion of strictly endodontic origin. A total of 59 patients were included in the study, according to specific selection criteria. Following the reflection of a full mucoperiosteal tissue flap, residual soft tissues were curetted, root ends were resected, and root-end cavities were prepared ultrasonically with a zirconium nitrate tip, and zinc oxide EBA-reinforced cement root-end fillings were placed. Thirty-two root-end management procedures were performed using magnification loupes and 39 using an endoscope. All cases followed for a period of 1 year were classified into 3 groups (success, uncertain healing, and failure) according to radiographic and clinical criteria. RESULTS: Of the 71 teeth evaluated at 1-year follow-up, 67 teeth (92.95%) successfully healed, 3 teeth had uncertain healing, and 2 failed. In the group using endoscopy, 94.9% of successful healing was achieved, while for the other group, 90.6% was recorded. We found no statistically significant differences in treatment results related to the arch (P = .20), post restoration (P = .21), or type of magnification device (P = .08). CONCLUSIONS: In the present study, adherence to a strict endodontic surgical protocol and the use of modern surgical endodontic procedures, together with visual magnifications, resulted in an overall high success rate.     

Significance of cyclin D1 expression in meningiomas: a preliminary study.

Forty-four evaluable patients with intracranial meningiomas were assessed for the expression of the cell-cycle regulator cyclin D1 and of proteins involved in proliferation and apoptosis such as PCNA, MIB-1, p53 and bcl-2. Analyses were carried out by western blot and immunohistochemistry after immediate processing of fresh tumor specimens. By western blot, expression of cyclin D1 significantly correlated with p53 (p=0.02) and with proliferative activity, as assessed by PCNA expression (p=0.0009). By immunohistochemistry, a significant relationship between cyclin D1 and the proliferation marker MIB-1 was confirmed (p=0.05), whereas significance with bcl-2 expression was not found (p=0.01). Moreover, although the association with tumor grade appeared of borderline statistical significance (p=0.07), all the grade II/III meningiomas showed increased expression of cyclin D1 and high proliferative activity. In conclusion, data from this preliminary study seem to suggest a potential value of the combined expression of cyclin D1 and proliferation indicators in defining subgroups of meningiomas with a more aggressive biological behavior.     

Idarubicin metabolism and pharmacokinetics after intravenous and oral administration in cancer patients: a crossover study

The pharmacokinetics and metabolism of 4-demethoxydaunorubicin (idarubicin, IDA) were studied in 21 patients with advanced cancer after i.v. (12 mg/m2) and oral (30-35 mg/m2) treatment according to a balanced crossover design. Patients were divided into four groups: subjects who showed normal liver and kidney function (group N), those who presented with normal kidney function and liver metastases (group L), those with kidney dysfunction (creatinine clearance, less than or equal to 60 l/h; group R), and those with both liver and kidney dysfunction (group LR). Five patients showed variations in liver or kidney function after the first treatment and were considered to be nonevaluable for the crossover study but evaluable for the liver/kidney function study; some of them appeared in different groups for the i.v. as opposed to p.o. treatments. After i.v. administration, IDA plasma levels followed a triphasic decay pattern. The main metabolite observed in all patients was the 13C-reduced compound (IDAol), which attained plasma levels 2-12 times higher than those of the parent compound. IDA pharmacokinetics was not dependent on the presence of liver metastases but was related to the integrity of kidney function. Analysis of variance indicated a significant correlation between IDA plasma clearance and creatinine clearance; it was also found that IDA plasma clearance was lower in patients whose creatinine clearance was less than 60 ml/min [group N, 122.8 +/- 44.0 l/h; group L, 104.4 +/- 27.7 l/h (P = 0.58) vs group R, 83.4 +/- 18.3 l/h (P = 0.037)]. The IDAol terminal half-life and mean residence time (MRT) were significantly increased in patients with impaired kidney function [MRT: group N, 63.6 +/- 10.8 h; group L, 69.9 +/- 10.2 h (P = 0.27) vs group R, 83.2 +/- 10.9 h (P = 0.025) and t1/2 gamma: group N, 41.3 +/- 10.1 h; group L, 47.0 +/- 7.4 h (P = 0.31) vs group R, 55.8 +/- 8.2 h (P = 0.025)]. After oral treatment, drug absorption occurred during in the first 2-4 h after IDA administration; a biphasic decay pattern was observed thereafter. The main metabolite observed in all patients was again IDAol. The AUC of IDAol was greater after oral administration than after i.v. treatment in proportion to the AUC of IDA (i.v.: AUC-IDAol/AUC-IDA, 2.4-18.9; p.o.: AUC-IDAol/AUC-IDA, 4.1-21.4). Following oral dosing, a substantial amount of 4-demethoxydaunomycinone (AG1) was found in 11/21 patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Relationship between maternal- and fetal-specific IgE

AIM: A positive correlation between maternal and cord-blood IgE levels is well documented for total IgEs, but not for specific IgEs. The difficulty in detecting specific cord-blood IgEs is due to their low concentrations, which hinder their dosage by low-sensitivity methods. The study aimed to correlate maternal and foetal specific IgEs against individual cow's milk proteins, detected by highly sensitive and specific techniques. METHODS: Cow's milk specific IgE detection was performed by chemiluminescence on 52 specimens of maternal and cord blood after cow's milk protein separation by 1D and 2D gel electrophoresis. Cow's milk protein (CMP) antigens were identified by mass spectrometry techniques. RESULTS: Specific IgEs for CMPs were found in 25/52 (48.1%) of maternal sera and in 19/52 (37%) of cord-blood sera. In order of decreasing frequency, the proteins found were BSA, IgG heavy chain, caseins and, in a single case, b-lactoglobulin. Positive cord-blood sera in all cases corresponded to a positive maternal result, and maternal and foetal immunoreactivity patterns were closely correlated. Moreover, in no case was there a positive cord-blood response with a negative maternal response. CONCLUSION: The study demonstrates a close relationship between maternal and cord-blood specific IgE patterns. The phenomenon observed could provide a model to elucidate the general production method of foetal IgEs, which might only be produced in the presence of both the corresponding maternal IgE and the related allergen.     

Telomerase activity in prognostic histopathologic features of melanoma.

BACKGROUND: Telomerase activity (TA) is believed to play a role in the regulation of senescence and to limit the number of cell divisions. The deregulation of telomerase appears to contribute to oncogenesis and the formation of immortal cell lines. As a result, it is believed that it could be used as a prognostic marker in melanoma. METHODS: TA was assayed by the polymerase chain reaction PCR-ELISA-based telomeric repeat amplification protocol (TRAP assay). One hundred and eight samples were distributed in four histological groups: 30 samples from primary cutaneous melanomas, 24 from peritumoural skin sites, 28 from benign melanocytic lesions, and 26 from normal skin sites as a control. RESULTS: TA was different among the four tested groups (Kruskall-Wallis test p<0.001), and increasing values of TA were observed progressing from normal skin to benign and then to malignant lesions. Among melanoma samples, there was a significant association between TA and ulceration (p=0.025), TA and vascular invasion (p=0.018) and TA and mitotic rate (p=0.029) (Mann-Whitney test). A linear regression analysis showed significant associations between the increase of TA with Breslow thickness (p=0.004) and the presence of satellites (p=0.002). CONCLUSIONS: We observed that TA had increased from control skin to peritumoural skin, and then to benign melanocytic lesions and finally to melanoma, suggesting tumour progression. TA showed higher values in the presence of some important histopathologic parameters related to poor prognosis in cutaneous melanoma such as ulceration, vascular invasion, satellites, high rates of mitosis, and in thicker tumours.