Phosphoinositide-3 kinases critically regulate the recruitment and survival of eosinophils in vivo: importance for the resolution of allergic inflammation

The phosphatidylinositol-3 kinase (PI3K) family of signaling enzymes plays a crucial role in leukocyte recruitment and activation and hence, likely regulates the induction and propagation phases of inflammation. However, little data have emerged showing a role for these processes in the resolution phase in models of in vivo inflammation. Here, we have evaluated the role of PI3K for the migration and survival of eosinophils in a model of allergic pleurisy in mice. Eosinophil accumulation in PI3Kgamma-deficient mice was inhibited at 48 h, as compared with wild-type mice but not at earlier time-points (6 and 24 h). Experiments with adoptive transfer of bone marrow showed that PI3Kgamma in eosinophils but not in non-bone marrow-derived cells was required for their accumulation. Systemic treatment with PI3K inhibitors before antigen challenge prevented the recruitment of eosinophils. This was associated with decreased Akt phosphorylation, interleukin-5 production, and eosinophil release from the bone marrow. Treatment with PI3K inhibitors 24 h after antigen challenge markedly cleared the accumulated eosinophils, an effect associated with inhibition of Akt phosphorylation and an increased number of apoptotic events. Altogether, our data demonstrate an important role of PI3Kgamma for the maintenance of eosinophilic inflammation in vivo, whereas other isoforms of PI3K may be relevant for the recruitment process.     

Developmental absence of maxillary lateral incisors in the Portuguese population

The aim of this study was to evaluate the prevalence and clinical manifestation of developmental absence of maxillary permanent lateral incisors in the Portuguese population. The study group comprised 16 771 patients observed between 1993 and 2000 at the Faculty clinic. Two hundred and nineteen patients were found to have missing upper lateral incisors (131 females and 88 males, with ages ranging between 3 and 71 years), a prevalence of 1.3 per cent in this population. Absence of these teeth was bilateral in 44.7 per cent of the patients; of the unilateral cases, 33 per cent occurred on the right side and 21.9 per cent on the left side. In children under 8 years of age (n = 12), two (0.26 per cent) also had developmental absence of the primary lateral incisors, one unilateral and the other bilateral. Among the 121 subjects with unilateral developmental absence, the contralateral maxillary lateral incisor was found to be microdont in 57.1 per cent (right lateral 23 per cent, left lateral 34.1 per cent), suggesting the possibility that microdontia represents a variable expression of the same developmental defect that results in absence.     

Positive Montenegro skin test among patients with sporotrichosis in Rio De Janeiro

Visceral leishmaniasis (VL) or kala-azar continues to persist as one of the major public health problems in many tropical countries. However, no effective treatment for radical cure of the disease is yet available. Miltefosine, an alkyl phospholipid compound, is the first orally effective drug, which has shown 98% cure rate of VL patients during phase III clinical trial in India. Since this drug requires long course of treatment and has long half-life, there are fairly good chances of emergence of resistance. Furthermore, this drug has produced severe side-effects in some of the cases.We therefore examined the possibility of minimizing these effects by applying miltefosine in lower doses in combination with picrloviv, an immunomodulator against Leishmania donovani in hamsters (Mesocricetus auratus). The picroliv per se showed no antileishmanaial potential. However, when given with suboptimal dose of miltefosine, it enhanced efficacy of the latter from 45 to 86% on day 7 post treatment and from 32 to 64% on day 28 post treatment. Interestingly, the efficacy of this combination was as good as the curative dose of miltefosine alone. Thus, this combination appears to offer a fruitful strategy for treatment of VL.     

Gestational diabetes management: a multidisciplinary treatment algorithm

Effective treatment of gestational diabetes is important as an attempt to avoid unfavorable maternal and fetal outcomes. The objective of this paper is to describe the available therapies to optimize gestational diabetes treatment and to suggest a multidisciplinary approach algorithm. Nutrition therapy is the first option for the majority of these pregnancies; light to moderate physical activity is recommended in the absence of obstetrical contraindications. Medical treatment is recommended if glycemic control is not achieved or if excessive fetal growth is detected by ultrasound. Insulin is the standard treatment although oral antidiabetic drugs have recently been considered an effective and safe option. The monitoring of gestational diabetes treatment includes capillary glucose measurements and evaluation of fetal abdominal circumference by ultrasound performed around the 28th gestational week.     

Orthodontic-orthognathic surgical treatment in a patient with Class II subdivision malocclusion: occlusal plane alteration

Despite the different orthodontic treatment options for patients with Class II subdivision malocclusions, the involvement of the skeletal structures is significant. It is desirable to combine orthodontic and surgical treatment to achieve a stable and better esthetic result, as illustrated in this case report. The occlusal plane was canted to the right as a part of the patient's facial asymmetry. Consequently, a 3-mm differential impaction of the maxilla on the left side allowed occlusal plane leveling. Mandibular rotation with advancement on the right side corrected the right Class II malocclusion. The successful attainment of the treatment goals was accomplished through teamwork and integration between the orthodontist and the maxillofacial surgeon.