A Phase I clinical trial of lodenafil carbonate, a new phosphodiesterase Type 5 (PDE5) inhibitor, in healthy male volunteers

Lodenafil carbonate is a new phosphodiesterase Type 5 (PDE5) inhibitor used in treatment of erectile dysfunction. Objective: The present study was conducted to evaluate the safety, tolerability, and pharmacokinetics of lodenafil carbonate after administering ascending (1 - 100 mg) single oral doses to healthy male volunteers (n = 33). Methods: The study was an open-label, dose-escalation, Phase I clinical trial involving the administration of single oral doses of lodenafil carbonate. Lodenafil carbonate was administered sequentially, escalating in single doses of 1 mg - 100 mg with a washout period of at least 1 week between each dose. The progression to the next dose was allowed after clinical and laboratory exams, Ambulatory Monitoring of Arterial Pressure (AMAP) without relevant clinical modifications and adverse events without clinical relevancy. Blood samples were collected at pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 h post-dosing. Plasma samples for measurement of lodenafil carbonate and lodenafil were analyzed by liquid chromatography coupled to tandem mass spectrometry. Results: No serious adverse events were observed, and none of the subjects discontinued the study due to intolerance. The AMAP measurements, clinical and laboratory exams and ECG revealed no significant changes even at higher doses. Lodenafil carbonate was not detected in any samples, indicating that it acts as a prodrug. The mean lodenafil pharmacokinetic parameters for t(max) and t(1/2) were 1.6 (+/- 0.4) h and 3.3 (+/- 1.1) h, respectively. This study demonstrated that lodenafil carbonate was well tolerated and showed a good safety profile in healthy male volunteers.

Assessment of cavitated and active non-cavitated caries lesions in 3-to 4-year-old preschool children: a field study

Background. The prevalence of early childhood caries (ECC) is high in developing countries; thus, sensitive methods for the early diagnosis of ECC are of prime importance to implement the appropriate preventive measures. Aim. To investigate the effects of the addition of early caries lesions (ECL) into WHO threshold caries detection methods on the prevalence of caries in primary teeth and the epidemiological profile of the studied population. Design. In total, 351 3-to 4-year-old preschoolers participated in this cross-sectional study. Clinical exams were conducted by one calibrated examiner using WHO and WHO + ECL criteria. During the exams, a mirror, a ball-ended probe, gauze, and an artificial light were used. The data were analysed by Wilcoxon and Mc-Nemar's tests (a = 0.05). Results. Good intra-examiner Kappa values at tooth /surface levels were obtained for WHO and WHO + ECL criteria (0.93 /0.87 and 0.75 /0.78, respectively). The dmfs scores were significantly higher (P < 0.05) when WHO + ECL criteria were used. ECLs were the predominant caries lesions in the majority of teeth. Conclusions. The results strongly suggest that the WHO + ECL diagnosis method could be used to identify ECL in young children under field conditions, increasing the prevalence and classification of caries activity and providing valuable information for the early establishment of preventive measures.

Teaching of the Integrated Management of Childhood Illness strategy in undergraduate nursing programs

Objective: To describe and analyze the teaching of the Integrated Management of hildhood Illness (IMCI) strategy on Brazilian undergraduate nursing programs. Method: Integrating an international multicentric study, a cross-sectional online survey was conducted between May and October 2010 with 571 undergraduate nursing programs in Brazil Results: Responses were received from 142 programs, 75% private and 25% public. 64% of them included the IMCI strategy in the theoretical content, and 50% of the programs included IMCI as part of the students’ practical experience. The locations most used for practical teaching were primary health care units. The ‘treatment’ module was taught by the fewest number of programs, and few programs had access to the IMCI instructional manuals. All programs used exams for evaluation, and private institutions were more likely to include class participation as part of the evaluation. Teaching staff in public institutions were more likely to have received training in teaching IMCI. Conclusion: In spite of the relevance of the IMCI strategy in care of the child, its content is not addressed in all undergraduate programs in Brazil, and many programs do not have access to the IMCI teaching manuals and have not provide training in IMCI to their teaching staff.

Contextual and individual assessment of dental pain period prevalence in adolescents: a multilevel approach

Abstract Background Despite evidence that health and disease occur in social contexts, the vast majority of studies addressing dental pain exclusively assessed information gathered at individual level. Objectives To assess the association between dental pain and contextual and individual characteristics in Brazilian adolescents. In addition, we aimed to test whether contextual Human Development Index is independently associated with dental pain after adjusting for individual level variables of socio-demographics and dental characteristics. Methods The study used data from an oral health survey carried out in São Paulo, Brazil, which included dental pain, dental exams, individual socioeconomic and demographic conditions, and Human Development Index at area level of 4,249 12-year-old and 1,566 15-year-old schoolchildren. The Poisson multilevel analysis was performed. Results Dental pain was found among 25.6% (95%CI = 24.5-26.7) of the adolescents and was 33% less prevalent among those living in more developed areas of the city than among those living in less developed areas. Girls, blacks, those whose parents earn low income and have low schooling, those studying at public schools, and those with dental treatment needs presented higher dental-pain prevalence than their counterparts. Area HDI remained associated with dental pain after adjusting for individual level variables of socio demographic and dental characteristics. Conclusions Girls, students whose parents have low schooling, those with low per capita income, those classified as having black skin color and those with dental treatment needs had higher dental pain prevalence than their counterparts. Students from areas with low Human Development Index had higher prevalence of dental pain than those from the more developed areas regardless of individual characteristics.

Early transplantation of human immature dental pulp stem cells from baby teeth to golden retriever muscular dystrophy (GRMD) dogs: Local or systemic?

Background:The golden retriever muscular dystrophy (GRMD) dogs represent the best available animal model for therapeutic trials aiming at the future treatment of human Duchenne muscular dystrophy (DMD). We have obtained a rare litter of six GRMD dogs (3 males and 3 females) born from an affected male and a carrier female which were submitted to a therapeutic trial with adult human stem cells to investigate their capacity to engraft into dogs muscles by local as compared to systemic injection without any immunosuppression. Methods Human Immature Dental Pulp Stem Cells (hIDPSC) were transplanted into 4 littermate dogs aged 28 to 40 days by either arterial or muscular injections. Two non-injected dogs were kept as controls. Clinical translation effects were analyzed since immune reactions by blood exams and physical scores capacity of each dog. Samples from biopsies were checked by immunohistochemistry (dystrophin markers) and FISH for human probes. Results and Discussion We analyzed the cells' ability in respect to migrate, engraftment, and myogenic potential, and the expression of human dystrophin in affected muscles. Additionally, the efficiency of single and consecutive early transplantation was compared. Chimeric muscle fibers were detected by immunofluorescence and fluorescent in situ hybridisation (FISH) using human antibodies and X and Y DNA probes. No signs of immune rejection were observed and these results suggested that hIDPSC cell transplantation may be done without immunosuppression. We showed that hIDPSC presented significant engraftment in GRMD dog muscles, although human dystrophin expression was modest and limited to several muscle fibers. Better clinical condition was also observed in the dog, which received monthly arterial injections and is still clinically stable at 25 months of age. Conclusion Our data suggested that systemic multiple deliveries seemed more effective than local injections. These findings open important avenues for further researches.

Early diagnosis of Gorlin-Goltz syndrome: case report

The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by keratocystic odontogenic tumors (KCOT) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article paper reports the case of a patient, a 10-year-old boy with NBCCS, emphasizing its clinical and radiographic manifestations. This study highlights the importance of health professionals in the early diagnosis of NBCCS and in a preventive multidisciplinary approach to provide a better prognosis for the patient.

Dental fluorosis in the primary dentition and intake of manufactured soy-based foods with fluoride

Background & aims: To identify manufactured soy-based products more recommended by pediatricians and nutritionists; to determine fluoride concentrations in these products; to evaluate children concerning fluorosis in primary teeth and its association with the consumption of soy-based products. Methods: Pediatricians and Nutritionists answered a questionnaire about soy-based products they most recommended to children. Fluoride concentrations of the 10 products more cited were analyzed with the ion-specific electrode. Dental fluorosis exams were performed in 315 4e6-year-old children. Dean’s Index was used to assess fluorosis. Among the children examined, 26 had lactose intolerance. Their parents answered a questionnaire about children’s and family’s profile, besides permitting the identification of soy-based products use. Chi-squared and Multivariable Logistic Regression tests were used (p < 0.05). Results: Fluoride content in the analyzed products ranged from 0.03 to 0.50 mg F /mL. Dental fluorosis was detected in 11% of the children, with very mild and mild degrees. Dental fluorosis in primary teeth was associated with lactose intolerance (p < 0.05), but there was no significant association with the use of manufactured soy-based products. Conclusions: Isolated consumption of soy-based products recommended by health professionals to children do not offer risk of dental fluorosis in primary teeth, which had a low prevalence and severity.

Neurovascular anatomical variations in the anterior palate observed on CBCT images

Objective: This study aimed to assess the presence of additional foramina and canals in the anterior palate region, through cone beam computed tomography (CBCT) images, describing their location, direction, and diameter. Materials & Methods: CBCT exams of 178 subjects displaying the anterior maxilla were included and the following parameters were registered: gender; age group; presence of additional foramina in the anterior palate (AFP) with at least 1 mm in diameter; location and diameter of AFP; and direction of bony canals associated with AFP. Results: Twenty-eight patients (15.7%) presented AFP and in total 34 additional foramina were registered. No statistical differences between patients with or without AFP were found for gender or age. The average diameter of AFP was 1.4 mm (range from 1 to 1.9 mm). Their location was variable, with most of the cases occurring in the alveolar process near the incisors or canines (n = 27). In 18 cases, AFP was associated with bony canals with upward or oblique direction toward the anterior nasal cavity floor. In 14 cases, the canal presented as a direct extension of the canalis sinuosus, in an upward direction laterally to the nasal cavity aperture. In two cases, the canal was observed adjacent to the incisive and joined the nasopalatine canal superiorly. Discussion: CBCT images have a crucial role in the recognition of anatomical variations by allowing detailed tridimensional evaluations. Additional foramina and canals in the anterior region of the upper jaw are relatively frequent. Practitioners should be aware and trained to identify these variations. Conclusions: Over 15% of the population studied had additional foramina in the anterior palate, between 1 mm and 1.9 mm wide, with variable locations. In most cases the canals associated with these foramina either presented as a direct extension of the canalis sinuosus, or coursed towards the nasal cavity floor.

Long-term cardiac changes in patients with systemic lupus erythematosus

Abstract Background The aim of this study was evaluate the late-onset repercussions of heart alterations of patients with systemic lupus erythematosus (SLE) after a 13-year follow up. Methods A historical prospective study was carried out involving the analysis of data from the charts of patients with a confirmed diagnosis of lupus in follow up since 1998. The 13-year evolution was systematically reviewed and tabulated to facilitate the interpretation of the data. Results Forty-eight patient charts were analyzed. Mean patient age was 34.5 ± 10.8 years at the time of diagnosis and 41.0 ± 10.3 years at the time of the study (45 women and 3 men). Eight deaths occurred in the follow-up period (two due to heart problems). Among the alterations found on the complementary exams, 46.2% of cases demonstrated worsening at reevaluation and four patients required a heart catheterization. In these cases, coronary angioplasty was performed due to the severity of the obstructions and one case required a further catheterization, culminating in the need for surgical myocardial revascularization. Conclusion The analysis demonstrated progressive heart impairment, with high rates of alterations on conventional complementary exams, including the need for angioplasty or revascularization surgery in four patients. These findings indicate the need for rigorous cardiac follow up in patients with systemic lupus erythematosus.

Coronoid process hyperplasia: an unusual cause of mandibular hypomobility

A large number of disorders affecting the masticatory system can cause restriction of mouth opening. The most common conditions related to this problem are those involving the temporomandibular joint (TMJ) and the masticatory muscles, when facial pain also is an usual finding. Congenital or developmental mandibular disorders are also possible causes for mouth opening limitation, although in a very small prevalence. Coronoid process hyperplasia (CPH) is an example of these cases, characterized by an excessive coronoid process growing, where mandibular movements become limited by the impaction of this structure on the posterior portion of the zygomatic bone. This condition is rare, painless, usually bilateral and progressive, affecting mainly men. Diagnosis of CPH is made based on clinical signs of mouth opening limitation together with imaging exams, especially panoramic radiography and computerized tomography (CT). Treatment is exclusively surgical. This paper presents a case of a male patient with bilateral coronoid process hyperplasia, initially diagnosed with bilateral disk displacement without reduction, and successfully treated with intraoral coronoidectomy. It is emphasized the importance of differential diagnosis for a correct diagnosis and, consequently, effective management strategy.

A comparative analysis of outpatient costs in HIV treatment programs

OBJECTIVE: To analyze the costs of human immunodeficiency virus (HIV) outpatient treatment for individuals with different CD4 cell counts in the Brazilian public health system, and to compare to costs in other national health systems. METHODS: A retrospective survey was conducted in five public outpatient clinics of the Brazilian national HIV program in the city of São Paulo. Data on healthcare services provided for a period of one year of HIV outpatient treatment were gathered from randomly selected medical records. Prices of inputs used were obtained through market research and public sector databases. Information on costs of HIV outpatient treatment in other national health systems were gathered from the literature. Annual costs of HIV outpatient treatment from each country were converted into 2010 U.S. dollars. RESULTS: Annual cost of HIV outpatient treatment for the Brazilian national public program was US$ 2,572.92 in 2006 in São Paulo, ranging from US$ 1,726.19 for patients with CD4 cell count > 500 to US$ 3,693.28 for patients with 51 < CD4 cell count < 200. Antiretrovirals (ARVs) represented approximately 62.0% of annual HIV outpatient costs. Comparing among different health systems during the same period, HIV outpatient treatment presented higher costs in countries where HIV treatment is provided by the private sector. CONCLUSION: The main cost drivers of HIV outpatient treatment in different health systems were: ARVs, other medications, health professional services, and diagnostic exams. Nevertheless, the magnitude of cost drivers varied among HIV outpatient treatment programs due to health system efficiency. The data presented may be a valuable tool for public policy evaluation of HIV treatment programs worldwide.

Ovarian response of Suffolk ewes to estrous synchronization using short-term protocol

The efficacy of estrus synchronization using short-term protocol was evaluated by ultrasound exams in Suffolk ewes during the pre-breeding season. The control Group (n = 12) was synchronized by treatment for 12 days with vaginal sponges impregnated with medroxyprogesterone acetate, and 400 IU eCG at sponge withdrawal. Experimental groups I, II and III kept the sponge in place for 4 days, and 100 µg of PGF2a was administered at sponge withdrawal. Additionally, Group I (n = 12) had 0.1 mg of estradiol benzoate (EB) administered during sponge placement and 50 µg of GnRH 48 hours after sponge removal. Group II (n = 6) had 35 mg of progesterone (P4) injected, and 0.1 mg of EB administered during sponge placement, 400 IU eCG at withdrawal and 48 hours after, 50 µg GnRH were administrated. Group III (n = 12) had 35 mg of P4 and 0.2 mg of EB administered at sponge placement, 400 IU eCG at withdrawal, and 50 µg of GnRH was administrated after 56 hours. Ovaries were monitored through ultrasound scanning. Concerning the first wave, no difference was detected between the control group and the experimental groups. However, the characteristics of ovulatory wave were significantly different between the groups. The duration of the follicular wave was shorter for Group III than for Group II. The follicle in Group I reached its maximum diameter before the Group II. The diameter of the follicle at the sponge withdrawal in the control group was larger than in Group I. After sponge withdrawal, the follicular growth rate was smaller in the control group than in Group III. The maximum diameter of the follicle in Group II was larger than in the other groups. The short-term protocol in which estrogen was used did not synchronize the emergence of the wave of follicular development.

Extra and intradural spinal Hemangioblastoma

Hemangioblastomas of the central nervous system (CNS) are low-grade highly vascularized tumors that may be sporadic or associated with Von Hippel-Lindau disease. Extradural hemangioblastomas are uncommon and those located extra and intradurally are even rarer. This study uses an illustrative case and literature review to discuss the difficulties to consider the correct diagnosis and to select the best surgical approach. A 57 years-old white male patient presented with myelopathy and right C5 radiculopathy. The images showed a lobulated, hourglass shaped, highly enhanced extra/intradural lesion that occupied the spinal canal and widened the C4-C5 right intervertebral foramen. Total resection of the intradural lesion was achieved through a posterior approach, but the extradural part could only be partially removed. Complete improvement was observed after four months of follow-up and the residual tumor has been followed up clinically and radiologically. Even though the preoperative impression was of a spinal schwannoma, the histopathological examination revealed grade I hemangioblastoma as per WHO. Despite their rarity, current complementary exams allow considering the diagnosis of hemangioblastoma preoperatively. That is essential to a better surgical planning in view of the particular surgical features of this lesion.

Co-presentation of human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis and adult-onset infective dermatitis associated with HTLV-1 infection

Background  Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), infective dermatitis associated with HTLV-1 (IDH), and various other clinical conditions. Several of these diseases can occur in association. Objective  Report an association of diseases related to HTLV-1 infection, occurring in an unusual age group. Methods  Dermatological and laboratory exams were consecutively performed in HTLV-1-infected individuals from January 2008 to July 2010 in the HTLV Outpatient Clinic at the Institute of Infectious Diseases “Emilio Ribas” in São Paulo, Brazil. Results  A total of 193 individuals (73 HAM/TSP and 120 asymptomatic carriers) were evaluated, three of which were associated with adult-onset IDH and HAM/TSP. In all three cases, the patients were affected by IDH after the development and progression of HAM/TSP-associated symptoms. Limitations  Small number of cases because of the rarity of these diseases. Conclusion  We draw attention to the possibility of co-presentation of adult-onset IDH in patients with a previous diagnosis of HAM/TSP, although IDH is a disease classically described in children. Thus, dermatologists should be aware of these diagnoses in areas endemic for HTLV-1 infection.

Adhesion molecules of detrusor muscle cells are influenced by a hypercholesterolemic diet or bladder outlet obstruction in a wistar rat model

Abstract Background Cell adhesion molecules (CAMs) are essential for maintaining tissue integrity by regulating intercellular and cell to extracellular matrix interactions. Cadherins and catenins are CAMs that are located on the cell membrane and are important for adherens junction (AJ) function. This study aims to verify if hypercholesterolemic diet (HCD) or bladder outlet obstruction (BOO) promotes structural bladder wall modifications specific to alterations in the expression of cadherins and catenins in detrusor muscle cells. Methods Forty-five 4-week-old female Wistar rats were divided into the following three groups: group 1 was a control group that was fed a normal diet (ND); group 2 was the BOO model and was fed a ND; and group 3 was a control group that was fed a HCD (1.25% cholesterol). Initially, serum cholesterol, LDL cholesterol and body weight were determined. Four weeks later, groups 1 and 3 underwent a sham operation; whereas group 2 underwent a partial BOO procedure that included a suture tied around the urethra. Six weeks later, all rats had their bladders removed, and previous exams were repeated. The expression levels of N-, P-, and E-cadherin, cadherin-11 and alpha-, beta- and gamma-catenins were evaluated by immunohistochemistry with a semiquantitative analysis. Results Wistar rats fed a HCD (group 3) exhibited a significant increase in LDL cholesterol levels (p=0.041) and body weight (p=0.017) when compared to both groups that were fed a normal diet in a ten-week period. We found higher β- and γ-catenin expression in groups 2 and 3 when compared to group 1 (p = 0.042 and p = 0.044, respectively). We also observed Cadherin-11 overexpression in group 3 when compared to groups 1 and 2 (p = 0.002). Conclusions A HCD in Wistar rats promoted, in addition to higher body weight gain and increased serum LDL cholesterol levels, overexpression of β- and γ-catenin in the detrusor muscle cells. Similar finding was observed in the BOO group. Higher Cadherin-11 expression was observed only in the HCD-treated rats. These findings may be associated with bladder dysfunctions that occur under such situations.