Naphthaquinones of Diospyros batocana

Root bark of West African tree DIOSPYROS BATOCANA H IERN, Ebenaceae, was examined. On the basis of chromatographic and spectral analysis it was shown to contain the naphtaquinones 7-methyljuglone, 2-methylnaphthazarin, biramentaceone, rotundiquinone, mamegakinone, diospyrin, diosquinone, isodiospyrin and batocanone. This last compound proved to be the (-)-enantiomer of isodiospyrin-2', 3'-epoxide. The probable existence of beta-dihydrodiospyrin, of a batocanone isomer and of an isodiospyrin diepoxide in this material is mentioned. The partial synthesis of two isomeric isodiospyrin di-epoxides is described.     

The most frequent neurologic disturbances. A contribution to the definition of topics for the programmatic content to the program of neurology in medical graduation

INTRODUCTION: Knowledge accumulation is overfilling the thematic content of medical graduation. Medical Schools must be alert to define a minimal content related with the most frequent disturbs. We intent to suggest topics for the minimal content, to the program of Neurology in medical graduation. METHOD: 1. To identify the places where young doctors are working outside the School Hospital (SH): we analysed the answers of the letters sent to 6415 resident - doctors (RD) in S?o Paulo's State and we made personal interview with 201 RD. 2. To verify the most frequent neuropsychiatric disturbs (ND) in the population: we made the analysis of the patient's diagnostic records in emergency room of three institutions: Municipal of Taubaté-SP, Municipal of S?o José dos Campos-SP and Faculty of Medicine of S?o Paulo Santa Casa de Misericórdia. RESULTS: 1. The RD are young and, outside the SH, they work in other emergency services. 2. The most frequent diagnosis in institutions were listed: alcoholism, cerebrovascular disease, coma, cranial trauma, dementia, dizziness, epilepsy, facial paralysis, faint, headache, hemiplegia or paraplegia, meningitis, others paralysis, periferical neuropathy and psychiatric disorders. CONCLUSIONS: Those diagnostics most frequent are relevant topics of the programmatic content to the program of Neurology in medical graduation.     

NEOPLASTIC DISEASE AND DELETION 22q11.2: A MULTICENTRIC STUDY AND REPORT OF TWO CASES

Deletion 22q11.2 is a chromosomal abnormality detected in young patients with clinical manifestations of the DiGeorge/velocardiofacial syndrome. Conotruncal heart defects are also associated with del22q11.2. An association of these cardiac malformations with neoplasias has been observed. Our series includes two cases of malignancies, a hepatoblastoma and a renal-cell carcinoma, arising in children with complex cardiac malformations. The aim of the study was to determine if the deletion at 22q11.2 was present and could be responsible for both pathological processes. Del22q11.2 was identified in both cases. Comparative genomic hybridization revealed terminal gains on chromosomes 1q and Xq and terminal loss on 1p in the hepatoblastoma, and gains in 1p, 12q, 16p, 20q, 22q, and whole chromosome 19 and loss of Xq in the renal-cell carcinoma. Our results confirm a common genetic basis for cardiac malformations, and del22q11.2 presents a risk factor for the development of pediatric tumours.     

An assessment of fructose-1,6-bisphosphate as an antimicrobial and anti-inflammatory agent in sepsis.

Tissue lesion mechanisms provoked by sepsis include the infectious process, inflammation, and cellular energy deficit. We chose to test fructose-1,6-bisphosphate (FBP) because of its possible anti-inflammatory and antimicrobial actions. Wistar rats were used and divided into three experimental groups: a control group (n=10), in which a capsule was introduced into the peritoneum of the animals; a septic group (n=10), in which a capsule containing non-sterile fecal matter was introduced together with Escherichia coli (1.5 x 10(9)CFU); and a septic group treated with FBP 500 mg/kg (n=10). The blood cell tests revealed that levels of leukocytes increased significantly in the septic group when compared to both the septic group treated with FBP and the control group. The blood cultures were 100% positive in both the septic group and the septic group treated with bisphosphorylated sugar. The antibiogram only revealed an inhibitory halo in the case of the antibiotic ampicillin, there was no such indication for FBP. The anti-inflammatory power of FBP remained at 60% for 5 h in the rats that received the carrageenan injection. What is more, the sugar reduced the levels of ionic calcium in relation to the control group. This data proves the validity of using FBP in the treatment of sepsis, possibly due to its anti-inflammatory rather than antimicrobial action.     

Estrogen-regulated progestin receptors are found in the midbrain raphe but not hippocampus of estrogen receptor alpha (ER alpha) gene-disrupted mice

Estrogen and progesterone may modulate serotonergic function through intracellular receptors, alpha (ER alpha) and/or beta (ER beta), and the progestin receptor (PR). Studies in macaque and rat suggest species differences in steroid action. Presently, we examined the mouse. To identify whether ER alpha is involved in estrogen induction of PR in midbrain raphe, we studied the ER alpha gene-disrupted (alpha ERKO) mouse. The hippocampus was examined as another estrogen/progestin-sensitive brain area reported to express ER alpha, ER beta, and PR. Female and male homozygous alpha ERKO and wildtype mice were gonadectomized and given estradiol benzoate or vehicle. Dual-label immunocytochemistry was performed for PR or ER alpha and the serotonin-synthesizing enzyme, tryptophan hydroxylase (TPH). Cells exhibiting PR immunoreactivity (PR-ir) or ER alpha-ir were observed in dorsal and median raphe and hippocampus in both sexes. No ER alpha-ir cells were observed in alpha ERKO brains. In raphe, PR-ir or ER alpha-ir often colocalized with TPH-ir. Thus, estrogen and progesterone may directly modulate gene expression in select serotonergic neurons via ER alpha and PR in female and male mice. Estrogen significantly increased the number of PR-ir cells, and the percentage of PR-ir cells colocalizing TPH-ir in both raphe nuclei, regardless of sex and genotype. Although less among alpha ERKO mice, the significant estrogen induction of PRs implicates the involvement of another ER, perhaps ER beta. In hippocampus, distinct estrogen-induced PR-ir cells were observed only in wildtype animals, demonstrating an ER alpha-mediated event in this forebrain region. Collectively, these findings suggest that estrogen can regulate the expression of one gene (the PR) via multiple mechanisms, based upon brain region.     

Do women fare worse: a metaanalysis of gender differences in traumatic brain injury outcome

OBJECT: The purpose of this metaanalysis was to investigate possible gender differences in traumatic brain injury (TBI) sequelae. The case fatality rates in patients after TBI have previously been shown to be significantly higher in women as compared with men. METHODS: A quantitative review of published studies of TBI outcome revealed eight studies (20 outcome variables) of TBI, in which outcome was reported separately for men and women. CONCLUSIONS: Outcome was worse in women than in men for 85% of the measured variables, with an average effect size of -0.15. Although clinical opinion is often that women tend to experience better outcomes than men after TBI, the opposite pattern was suggested in the results of this metaanalysis. However, this conclusion is limited by the fact that, in only a small percentage of the total published reports on TBI outcome, was outcome described separately for each sex. A careful, prospective study of sex differences in TBI outcome is clearly needed.     

Purification and characterization of a novel peptide with antifungal activity from Bothrops jararaca venom.

Different peptides have been isolated from a wide range of animal species. It is has become increasingly clear that due to the development of antibiotic-resistant microbes, antibacterial and antifungal peptides have attracted the attention in recent years, in order to find new therapeutic agents. In this work, a novel peptide with high inhibitory activity against fungi growth have been isolated from the venom of the Brazilian snake Bothrops jararaca. A Sephacryl S-100 gel filtration column was employed for further separation of proteins. The FV fraction with high antifungal activity was named Pep5Bj, pooled and submitted to reverse-phase chromatography in HPLC. The fraction containing the isolated peptide inhibited the growth of different phytopathogenic fungi (Fusarium oxysporum and Colletotrichum lindemuthianum) and yeast (Candida albicans and Saccharomyces cerevisiae). The peptide minimal inhibitory concentration is comparable to other known antifungal peptides, like insect defensins and cecropins, found in the last years in a large diversity of animals. We investigate F. oxysporum cells membrane permeabilization using SYTOX Green uptake, an organic compound that fluoresces upon interaction with nucleic acids after penetration in cell with compromised plasma membranes. When viewed under fluorescence optical microscopy, F. oxysporum cells exposed to Pep5Bj display strong SYTOX Green fluorescence in the cytosol, especially in the nuclei. The SYTOX Green data suggested that this effect is related to membrane permeabilization. The molecular masses of this peptide was obtained by MALDI-TOF spectrometry and corresponded to 1370Da.     

Effect of reminder cards on compliance with antihypertensive medication

Objective Poor compliance to antihypertensive medications has been identified as a primary cause of uncontrolled blood pressure (BP), with consequent increases in hypertension‐related morbidity and mortality. Therefore, any measure known to improve compliance should be encouraged. This study assessed the impact of reminder cards on compliance to antihypertensive therapy. Method A field trial was undertaken in pharmacies located in the districts of Lisbon and Porto. Eligible participants comprised those aged 30–74 years, prescribed an angiotensin‐converting enzyme inhibitor (ACEI) in monotherapy, and taken on a once‐daily regimen. Patients were allocated to control group (CG) or intervention group (IG), the latter being provided with a reminder card, an alarm‐type device due to remind the patient of the time to take his medication. Patients were monitored monthly during 3 months for compliance and blood pressure control. Key findings Seventy‐one patients participated in the study (intervention: 35; control group: 36). Compliance was similar between the groups in the first 2 months of follow‐up (97.1% IG vs 94.9% CG at first follow‐up and 97.5% IG vs 94.2% CG at second follow‐up) and higher in the intervention group at the end of the study (97.3% IG vs 87.3% CG; P = 0.011). There were no mean blood pressure differences between compliant and non‐compliant subjects at the end of the study (P value for differences in systolic BP (P_syst) = 0.580; and P value for differences in diastolic BP (P_dlast) = 0.175). Conclusion This small‐scale study indicates a possible positive impact on patients' compliance resulting from the use of reminder cards. However, this needs confirming in larger scale studies with longer monitoring periods.     

Anti-inflammatory effects of fructose-1,6-bisphosphate on carrageenan-induced pleurisy in rat.

In the present study, we evaluated the effect of fructose-1,6-bisphosphate (FBP), a high energy intermediate metabolite of glycolysis, in an acute model of lung injury. Injection of carrageenan into the pleural cavity of rats elicited an acute inflammation response characterized by a fluid accumulation in the pleural cavity which contained a large number of polymorphonuclear neutrophils. FBP (500mg/kg) attenuated the inflammation parameters: exudate volume, total leukocytes and the number of polymorphonuclear leukocytes, but the protein concentration in the exudate was not significantly affected by treatment with FBP. The precise site and mechanism of the anti-inflammatory effect was not addressed, considering the diverse pharmacological actions of FBP. This drug has anti-inflammatory actions suggesting that it may represent a novel strategy for the modulation of inflammatory response.