Low dose of propranolol down-modulates bone resorption by inhibiting inflammation and osteoclast differentiation

BACKGROUND AND PURPOSE

Bones are widely innervated, suggesting an important role for the sympathetic regulation of bone metabolism, although there are controversial studies. We investigated the effects of propranolol in a model of experimental periodontal disease.

EXPERIMENTAL APPROACH

Rats were assigned as follows: animals without ligature; ligated animals receiving vehicle and ligated animals receiving 0.1, 5 or 20 mg·kg⁻¹ propranolol. After 30 days, haemodynamic parameters were measured by cardiac catheterization. Gingival tissues were removed and assessed for IL-1β, TNF-α and cross-linked carboxyterminal telopeptides of type I collagen (CTX) by elisa, or intercellular adhesion molecule 1 (ICAM-1), receptor activator of NF-κ B ligand (RANKL) and osteoprotegerin (OPG) by Western blot analysis. Sections from the mandibles were evaluated for bone resorption. Also, we analysed the ability of propranolol to inhibit osteoclastogenesis in vitro.

RESULTS

Propranolol at 0.1 and 5 mg·kg⁻¹ reduced the bone resorption as well as ICAM-1 and RANKL expression. However, only 0.1 mg·kg⁻¹ reduced IL-1β, TNF-α and CTX levels as well as increased the expression of OPG, but did not alter any of the haemodynamic parameters. Propranolol also suppressed in vitro osteoclast differentiation and resorptive activity by inhibiting the nuclear factor of activated T cells (NFATc)1 pathway and the expression of tartrate-resistant acid phosphatase (TRAP), cathepsin K and MMP-9.

CONCLUSIONS AND IMPLICATIONS

Low doses of propranolol suppress bone resorption by inhibiting RANKL-mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters.     

Intracranial aneurysms associated with a double origin of the posterior inferior cerebellar artery

The posterior inferior cerebellar artery (PICA) frequently has a variable course and target territory. However, double origin PICA is a rare finding. Its significance is uncertain, but it has been associated with intracranial aneurysms localized at the PICA proper or at a distant site. The presence of this variation imposes specific challenges. We describe two cases of double origin PICA, one of them associated with an ipsilateral PICA aneurysm. The role of this finding was critically reviewed. A literature search identified 23 cases of double origin PICA, including both cases reported in this paper. Intracranial aneurysms were strongly associated with double origin PICA (71% in 21 detailed cases of double origin PICA). The current patient harboring a PICA aneurysm was successfully treated by endovascular trapping. In the setting of double origin PICA aneurysms, this variation beneficially affects the treatment choice once the two limbs enable the safe sacrifice of the channel involved, with preservation of blood flow through the other channel.     

Use of parasitological culture to detect Leishmania (Leishmania) chagasi in naturally infected dogs

In Brazil, although the domestic dog is a major target for the control actions for visceral leishmaniasis, knowledge gaps of the Leishmania species present in those animals still exist in many endemic areas. The objective of this study was the use of parasitological culture as a diagnosis tool and identification of species of Leishmania and other trypanosomatids in the canine population in the city of Cuiaba/Mato Grosso. Biological samples such as blood, intact skin fragments, cutaneous ulcers, and bone marrow were collected during a cross-sectional study and cultured on biphasic medium (Novy-MacNeil-Nicolle [NNN]/Schneider's). Leishmania isolates were characterized through isoenzyme electrophoresis. Isolates were obtained from 11.2% (n=54) of the 482 animals studied considering the different anatomical sites investigated. Leishmania chagasi was confirmed in 8.3% (n=40) dogs and Trypanosoma caninum in 2.9% (n=14). The sample of intact skin presented a higher chance of isolation of L. chagasi in symptomatic dogs and bone marrow in asymptomatic dogs (p<0.05). The results presented in this study emphasize the value of culture and confirm, for the first time, the circulation of L. chagasi in the canine population in different neighborhoods of the city of Cuiaba and broaden the knowledge of the geographical distribution of T. caninum in Brazil.     

The decision of women for cesarean birth: a case study in two units of the supplementary health care system of the State of Rio de Janeiro

Cesarean section rates are very high in Brazil mainly in private hospitals, probably due to socioeconomic and cultural factors. The objective of this study was to describe socioeconomic, demographic, cultural and reproductive characteristics of women in the postpartum period and the factors that had determined their decision for caesarean section in two units of the supplementary health care system of the State of Rio de Janeiro. The study population was composed of 437 women that had vaginal or caesarean childbirths in the two selected units. Data were collected by means of interviews with mothers and consultation of hospital records. The factors associated with the decision for cesarean section as mode of delivery were evaluated using non-conditional logistic regression analysis and following the hierarchic models established at three definite moments. Although 70% of the women had no initial preference for cesarean section, 90% of them had this mode of birth. It was verified that, despite their initial desire, the interaction with the health services resulted in cesarean section as mode of birth. Educative actions directed to pregnant women and to the public at large as well as changes in the childbirth care model can be promising strategies for reverting this picture.     

Death Ideation in Cancer Patients: Contributing Factors

Advances in cancer research and therapy have improved prognosis and the quality of life of many patients. However, previous epidemiological studies in oncologic patients have shown an increased risk of suicide. Suicidal thoughts, relatively well known in those terminally ill, may be just as important for cancer patients who are survivors or are living with the disease. Nonetheless, there is a relative paucity of data about suicidality in this setting. The authors conducted a prospective observational study to identify death thoughts and to explore the factors associated with suicidal ideation in cancer patients. A sample of 130 patients referred for psychiatric consultation was obtained following informed consent and authorization from the local ethics committee. A semistructured interview assessed sociodemographic data, psychosocial support, and information regarding the cancer process and its treatment. Psychometric instruments were used to evaluate psychopathology, namely the Hospital Anxiety and Depression Scale, the Beck Hopelessness Scale, and the Beck Scale for Suicide Ideation. Psychiatric diagnoses were obtained through the application of the Mini International Neuropsychiatric Interview. Death ideation was identified in 34.6% of patients, yet only 10% had active suicidal thoughts. Risk of suicide was associated with female gender, a psychiatric diagnosis (major depressive disorder, panic disorder, or dysthymia), difficult interpersonal relationships, associated pain, high hopelessness, and depressive and anxiety symptoms. Although suicidal thoughts are frequent in cancer patients at different stages of disease, most are transitory. Risk factors for suicidal ideation have been identified, such as depression, hopelessness, uncontrolled pain, and difficult interpersonal relationships. Further assessment is necessary to identify those at higher risk of attempting suicide, and underlying psychiatric disorders should be vigorously treated.     

Nerve growth factor restores mRNA levels and the expression of neuropeptides in the suprachiasmatic nucleus of rats submitted to chronic ethanol treatment and withdrawal

Chronic ethanol treatment and withdrawal from alcohol decrease the synthesis and expression of neuropeptides in the hypothalamic suprachiasmatic nucleus. Given the existing evidence that neurotrophins modulate the synthesis and expression of neurotransmitters/neuromodulators in the mature brain, we have hypothesized that such alterations might result from the reduced biological activity or brain content of neurotrophic factors. To test this possibility, nerve growth factor (NGF) was delivered intraventricularly, over a 4-week period, to rats submitted to ethanol treatment for 6 months and to withdrawn rats. Vasopressin (AVP) and vasoactive intestinal polypeptide (VIP), and the respective mRNAs were detected by immunocytochemistry and in situ hybridization histochemistry, and their levels estimated using stereological methods and densitometry. In ethanol-treated and withdrawn rats, NGF produced increases in the number of AVP- and VIP-immunostained neurons to values identical to those of controls. Corresponding variations were detected in AVP and VIP mRNA levels, which indicates that NGF restored the expression of AVP and VIP by enhancing neuropeptide synthesis. These findings show that NGF can correct the changes induced by chronic ethanol treatment and withdrawal in the gene expression and protein content of the neuropeptides synthesized by suprachiasmatic neurons. They also reveal that NGF plays an important role in the maintenance of the neurochemical phenotype of the suprachiasmatic nucleus in the adult rat. Because suprachiasmatic neurons do not express trkA, NGF might have exerted its effects either through direct signalling of suprachiasmatic neurons via p75^NTR activation or, indirectly, by enhancing the activity of the cholinergic and/or glutamatergic afferents to the suprachiasmatic nucleus, or both.     

Morphometric study of the frontal cortex in subacute sclerosing panencephalitis

In biopsic material collected from the frontal cortex of 6 patients with subacute sclerosing panencephalitis (SSPE) and 5 patients with posterior fossa tumors, we estimated the neuronal and synaptic numerical densities as well as the mean volume of the neurons from layers II and III. The thickness of these layers was also determined. The evaluation of the layer's thickness suggested that there was no difference in the shrinkage in SSPE as compared to controls. No differences were found between the neuronal numerical densities and the neuronal soma sizes from SSPE and controls. Conversely the synaptic numerical density was reduced in SSPE. Given the maintenance of the neuronal numerical density in the frontal cortex of patients with SSPE, the presence of a decreased density of synapses must be regarded as a consequence of the dendritic and axonal degeneration that we previously described in this condition. It must then be borne in mind that SSPE's functional and behavioral changes might spring from alterations of the frontal cortex neuronal circuitry.