Teleantagonism: A pharmacodynamic property of the primary nociceptive neuron

Previous work from our group showed that intrathecal (i.t.) administration of substances such as glutamate, NMDA, or PGE₂ induced sensitization of the primary nociceptive neuron (PNN hypernociception) that was inhibited by a distal intraplantar (i.pl.) injection of either morphine or dipyrone. This pharmacodynamic phenomenon is referred to in the present work as “teleantagonism”. We previously observed that the antinociceptive effect of i.t. morphine could be blocked by injecting inhibitors of the NO signaling pathway in the paw (i.pl.), and this effect was used to explain the mechanism of opioid-induced peripheral analgesia by i.t. administration. The objective of the present investigation was to determine whether this teleantagonism phenomenon was specific to this biochemical pathway (NO) or was a general property of the PNNs. Teleantagonism was investigated by administering test substances to the two ends of the PNN (i.e., to distal and proximal terminals; i.pl. plus i.t. or i.t. plus i.pl. injections). We found teleantagonism when: (i) inhibitors of the NO signaling pathway were injected distally during the antinociception induced by opioid agonists; (ii) a nonselective COX inhibitor was tested against PNN sensitization by IL-1β; (iii) selective opioid-receptor antagonists tested against antinociception induced by corresponding selective agonists. Although the dorsal root ganglion seems to be an important site for drug interactions, the teleantagonism phenomenon suggests that, in PNNs, a local sensitization spreads to the entire cell and constitutes an intriguing and not yet completely understood pharmacodynamic property of this group of neurons.     

Spontaneous coronary artery dissection: A single-center case series and literature review

Background

Spontaneous coronary artery dissection (SCAD) is an unusual cause of acute coronary syndrome (ACS). Better recognition and diagnosis has raised awareness of this condition. However, the pathophysiology of SCAD and its prognosis are still little understood. We aimed to investigate the characteristics and prognosis of patients with SCAD, and subsequently performed a review of literature.

Reproductive Biology of Triatoma brasiliensis (Hemiptera,Triatominae) during the Imaginal Molt

The triatomines are vectors of the protozoan Trypanosoma cruzi, etiologic agent of Chagas disease. These insects are sexually active after the imaginal molt. Some aspects have been studied in Triatoma brasiliensis during the imaginal molt, such as autogeny in virgin females and the relationship between blood ingestion by fifth instar nymph and the realization of the imaginal molt. Thus, to aid in the understanding of reproductive biology and developmental physiology of these vectors, this article analyzes the spermatogenesis of T. brasiliensis during the imaginal molt. The analysis of the seminiferous tubules from males in the fifth instar during imaginal molt has demonstrated that T. brasiliensis has only a few spermatids and a plentiful quantity of sperm. Thus, we suggest that during imaginal molt the cell division is disrupted aiming to reduce energy costs and the differentiation into sperm is stimulated to ensure the paternity of the adult male.Chagas disease is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi and transmitted to humans by contact with feces of triatomine bugs, known as “kissing bugs.”¹ These vectors have a typical hemimetabolous life cycle, from eggs through five nymphal instars (N1, N2, N3, N4, and N5) to adult males and females. The transition from the fifth instar nymph to adult is named imaginal molt. During this process it occur some corporal changes, such as the emergence of wings,² exocrine glands (metasternal and Brindley''s glands)^3,4 and development of the reproductive system.^5–8Some aspects have been studied in Triatoma brasiliensis Neiva, 1911 during the imaginal molt, such as autogeny in virgin females⁹ and the relationship between blood ingestion by N5 and the realization of the imaginal molt.¹⁰ This triatomine species is the most important Chagas disease vector in the Brazilian northeast.^11,12 Thus, to aid in the understanding of the reproductive biology and developmental physiology of these vectors, this article analyzes the spermatogenesis of T. brasiliensis during the imaginal molt.Five males in the fifth instar nymphs of T. brasiliensis were isolated and during imaginal molt their testicles were removed and fixed in methanol: acetic acid (3:1). They had been assigned by the “Triatominae Insectarium” within the Department of Biological Sciences, in the College of Pharmaceutical Sciences, at Sao Paulo State University''s “Júlio de Mesquita Filho,” Araraquara campus. The colony was formed from T. brasiliensis collected in intradomiciliary region of the municipality Olho d''Água, State of Paraiba, Brazil in the day April 17, 2008.Seminiferous tubules were first shredded, smashed, and the microscope slides were set in liquid nitrogen. They were then stained with the lacto-acetic orcein cytogenetic technique.^13,14 On the basis of the analysis of slides, it was observed that the N5 nymphs, during imaginal molt, have only one of the phases of spermatogenesis, that is, the spermiogenesis. This is represented by the presence of spermatids (Figure 1A –C) and sperm (Figure 1D).Open in a separate windowFigure 1.Spermiogenesis in Triatoma brasiliensis. Note the elongation of spermatids (A–C) and sperm (D). Bar: 10 μm.Spermatogenesis is the process by which sperms are produced in the seminiferous tubules. It consists of three different phases: spermatocitogenesis, which is a phase of multiplication; meiosis, which is the division phase; and spermiogenesis, which is the differentiation phase.¹⁵Perez and others,¹⁶ reported that in some cases fifth instar nymph have mature gonads. Mello and collaborators,¹⁷ analyzed fifth instar nymph of Triatoma infestans and observed the presence of spermatogonia, spermatocytes (metaphase), spermatids, and sperms. However, during imaginal molt of T. brasiliensis there are only a few spermatids and a plentiful quantity of sperm were observed, and we suggest that during imaginal molt, the cell division is disrupted aiming to reduce energy costs, and the differentiation into sperm is stimulated to ensure the paternity of the adult male.There are some offensive mechanisms that increase the chances to ensure the paternity, such as the characteristics of the genitalia,¹⁸ the seminal fluid,¹⁹ and the courtship behavior.²⁰ Taking it into account, we suggest that the excessive increase of sperms during imaginal molt also increase the chances for the paternity.Thus, we suggest that during the imaginal molt T. brasiliensis showed changes in the reproductive biology of development and physiology to decrease the energy cost, ensuring that the molt occur and mainly to increase the chance of paternity in adults. These results provide important information for understanding the biology of this important vector of the Chagas disease. However, we highlight that new species and a larger number of triatomines should be analyzed to characterize whether this phenomenon occurs in all species of Triatominae subfamily.     

The influence of gender on symptoms associated with obstructive sleep apnea

Background

It has been reported that the clinical expression of obstructive sleep apnea (OSA) may differ in women and men.

Objective

The objective of this study was to evaluate the influence of gender on reported OSA-related symptoms in a large clinical population of patients.

Methods

The database from the sleep laboratory of a tertiary care center was examined. Adult patients who had undergone a diagnostic polysomnography and completed the Berlin questionnaire, a sleep questionnaire, and the Epworth sleepiness scale were selected. Multiple logistic regression analysis was performed to assess the relationship between OSA-associated symptoms and different potential explanatory variables.

Results

The study sample included 1084 patients, median age was 53 years, 46.5% (504) were women, 72.7% (788) had OSA (apnea/hypopnea index ≥?5), and 31.2% were obese. After adjusting for age, body mass index, and apnea/hypopnea index, men were more likely to report snoring (OR 4.06, p?<?0.001), habitual or loud snoring (OR 2.34, p?<?0.001; 2.14, p?<?0.001, respectively) and apneas (OR 2.44, p?<?0.001), than women. After controlling for multiple variables, female gender was an independent predictive factor for reported tiredness (OR 0.57, p 0.001), sleep onset insomnia (OR 0.59, p 0.0035), and morning headaches (OR 0.32, p?<?0.001). Reports of excessive daytime sleepiness, nocturia, midnight insomnia, and subjective cognitive complaints were not significantly associated with gender.

Conclusion

Women with OSA were more likely to report tiredness, initial insomnia, and morning headaches, and less likely to complain of typical OSA symptoms (snoring, apneas) than men.

     

Voriconazole Enhances the Osteogenic Activity of Human Osteoblasts In Vitro through a Fluoride-Independent Mechanism

Periostitis, which is characterized by bony pain and diffuse periosteal ossification, has been increasingly reported with prolonged clinical use of voriconazole. While resolution of clinical symptoms following discontinuation of therapy suggests a causative role for voriconazole, the biological mechanisms contributing to voriconazole-induced periostitis are unknown. To elucidate potential mechanisms, we exposed human osteoblasts in vitro to voriconazole or fluconazole at 15 or 200 μg/ml (reflecting systemic or local administration, respectively), under nonosteogenic or osteogenic conditions, for 1, 3, or 7 days and evaluated the effects on cell proliferation (reflected by total cellular DNA) and osteogenic differentiation (reflected by alkaline phosphatase activity, calcium accumulation, and expression of genes involved in osteogenic differentiation). Release of free fluoride, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) was also measured in cell supernatants of osteoblasts exposed to triazoles, with an ion-selective electrode (for free fluoride) and enzyme-linked immunosorbent assays (ELISAs) (for VEGF and PDGF). Voriconazole but not fluconazole significantly enhanced the proliferation and differentiation of osteoblasts. In contrast to clinical observations, no increases in free fluoride levels were detected following exposure to either voriconazole or fluconazole; however, significant increases in the expression of VEGF and PDGF by osteoblasts were observed following exposure to voriconazole. Our results demonstrate that voriconazole can induce osteoblast proliferation and enhance osteogenic activity in vitro. Importantly, and in contrast to the previously proposed mechanism of fluoride-stimulated osteogenesis, our findings suggest that voriconazole-induced periostitis may also occur through fluoride-independent mechanisms that enhance the expression of cytokines that can augment osteoblastic activity.     

Associations Between Sex Hormone Levels and Periodontitis in Men: Results From NHANES III

Background: Sex hormones are linked to inflammation and bone turnover. The goal of this study is to explore the association between sex hormone levels and periodontitis in men using data from the third National Health and Nutrition Examination Survey (NHANES III). Methods: Data from 755 men (aged ≥30 years), including serum levels of testosterone, estradiol, sex hormone binding globulin, and androstenediol glucuronide, were analyzed. Calculated bioavailable testosterone (CBT) and estradiol‐to‐testosterone ratio were calculated. Periodontitis was defined using the latest classification of extent and severity of periodontitis for NHANES data (≥2 interproximal sites with ≥3 mm attachment loss, ≥2 interproximal sites with probing depth [PD] ≥4 mm not on the same tooth, or one site with PD ≥5 mm). Sex hormones were evaluated as categorized and continuous variables. Correlations between the presence and severity of periodontitis and levels of sex hormones were determined and expressed as odds ratios (ORs). Results: When adjusted for confounding factors, high total testosterone (TT) and CBT levels correlated with both the prevalence (OR [95% confidence interval (CI)], 2.1 [1 to 4.5] and 3.9 [1 to 14.8], respectively) and severity (OR [95% CI], 2.1 [1 to 4.3] and 3.4 [1.2 to 9.8]) of periodontitis. When continuous variables were used, the ORs (95% CIs) for presence and severity of periodontitis were 1.4 (0.6 to 3.3) and 1.5 (0.6 to 3.6) for TT and 1.3 (0.9 to 1.9) and 1.3 (0.9 to 1.8) for CBT, respectively. Conclusions: These findings are consistent with the existence of an association of periodontitis with sex hormone levels, especially testosterone, in men.     

Postural education and behavior among students in a city in southern Brazil: student postural education and behavior

[Purpose] The aim of the present study was to assess the knowledge of the spine and posture among adolescent female students and to determine if they had access to postural education in or outside school. [Subjects and Methods] This was an epidemiological survey of a representative sample of 495 female students aged 14 to 18 years attending a regular secondary school in São Leopoldo, RS, Brazil. Data were collected through a questionnaire. [Results] The results showed that 16.8% of teens did not know what a spine was, 8.3% had no knowledge of posture, and 61% reported receiving no posture education. Posture awareness was associated only with posture while using a computer, while having postural education class was not associated with any postural behavior. [Conclusion] The results showed that, although most students are familiar with the spine and posture, a sizable group is not, and over half had no postural education. These findings suggest that inclusion of postural education programs in schools should be encouraged in order to promote health and prevent diseases related to the spine.Key words: Posture, Adolescent health, School health     

Outcomes of a Peritoneal Dialysis Program in Remote Communities Within Colombia

♦ Background and Objective: Colombia is a country of diverse geographic regions, some with mountainous terrain that can make access to urban areas difficult for individuals who live in remote areas. In 2005, a program was initiated to establish remote peritoneal dialysis (PD) centers in Colombia to improve access to PD for patients with end-stage renal disease who face geographic or financial access barriers.♦ Patients and Methods: The present study was a multi-center cohort observational study of prevalent home PD patients who were at least 18 years of age and were being managed by one of nine established remote PD centers in Colombia over a 2-year period. Data were collected from clinical records, databases, and patient interviews. Patient survival, incidence of peritonitis, and rate of withdrawal from PD therapy were assessed.♦ Results: A total of 345 patients were eligible for the study. The majority (87.8%) of patients lived on one to two times a minimum monthly salary (equivalent to US$243 – US$486). On average, patients traveled 1.2 hours and 4.3 hours from their home to their remote PD center or an urban reference renal clinic, respectively. The incidence rate of peritonitis was 2.54 episodes per 100 patient-months of therapy. A bivariate analysis showed a significantly higher risk of peritonitis in patients who were living on less than one times a monthly minimum salary (p < 0.05) or who had a dirt, cement, or unfinished wood floor (p < 0.05). The 1-year and 2-year patient survival rates were 92.44% and 81.55%, respectively. The 1-year and 2-year technique survival rates were 97.27% and 89.78%, respectively.♦ Conclusions: With the support of remote PD centers that mitigate geographic and financial barriers to healthcare, home PD therapy is a safe and appropriate treatment option for patients who live in remote areas in Colombia.     

Dental and skeletal changes in mild to moderate Class II malocclusions treated by either a Twin-block or Xbow appliance followed by full fixed orthodontic treatment

Objective:To compare the short-term skeletal and dental effects of two-phase orthodontic treatment including either a Twin-block or an XBow appliance.Materials and Methods:This was a retrospective clinical trial of 50 consecutive Class II cases treated in a private practice with either a Twin-block (25) or XBow (25) appliance followed by full fixed orthodontic treatment. To factor out growth, an untreated Class II control group (25) was considered.Results:A MANOVA of treatment/observation changes followed by univariate pairwise comparisons showed that the maxilla moved forward less in the treatment groups than in the control group. As for mandibular changes, the corpus length increase was larger in the Twin-block group by 3.9 mm. Dentally, mesial movement of mandibular molars was greater in both treatment groups. Although no distalization of maxillary molars was found in either treatment group, restriction of mesial movement of these teeth was seen in both treatment groups. Both treatment groups demonstrated increased mandibular incisor proclination with larger increases for the XBow group by 3.3°. The Wits value was decreased by 1.6 mm more in the Twin-block group. No sex-related differences were observed.Conclusions:Class II correction using an XBow or Twin-block followed by fixed appliances occurs through a relatively similar combination of dental and skeletal effects. An increase in mandibular incisor inclination for the XBow group and an increased corpus length for the Twin-block group were notable exceptions. No overall treatment length differences were seen.     

Relationship between foot posture measurements and force platform parameters during two balance tasks in older and younger subjects

[Purpose] The aim of this study was to compare age-related differences in balance and anthropometric posture measurements of the foot and to determine any relationship between them. [Subjects and Methods] Sixty-eight older and 42 younger adults participated in this study. Foot posture was tested for four domains: 1) hallux flexion and extension range of motion using a goniometer, 2) navicular height and 3) length of the foot using a pachymeter, and 4) footprint (width of forefoot, arch index and hallux valgus). Balance was tested under two conditions on a force platform: bipodal in 60-s trials and unipodal in 30-s trials. The sway area of the center of pressure and velocity in the anteroposterior and mediolateral directions were computed. [Results] Older individuals showed significantly poorer balance compared with younger adults under in the unipodal condition (center of pressure area 9.97 vs. 7.72 cm²). Older people presented a significantly lower hallux mobility and higher values for width of the forefoot and transverse arch index than younger adults. The correlations between all foot posture and center of pressure parameters varied across groups, from weak to moderate (r −0.01 to −0.46). Low hallux mobility was significantly related to higher center of pressure values in older people. [Conclusion] These results have clinical implications for balance and foot posture assessments.Key words: Posture, Aging, Foot