Bronchodilators in asthma: bypassing controversies

Inhaled bronchodilators are used in acute asthma for relief of airway obstruction. Continuous monotherapy with beta 2 adrenergic can increase hyperresponsiveness because these drugs do not control inflammation. Asthma mortality and morbidity have been related to an increased beta 2-agonists use. Epidemiologic data however do not show a cause/effect relationship. Until controversies are cleared on, beta 2-agonists should be used for relieving acute asthma attacks, for preventing exercise-induced bronchospasm and eventually on an as needed basis. Long acting beta 2-agonists can be effective in moderate/severe asthma. Daily short acting beta 2 use by inhalation, a partial clinical response and its overuse in acute asthma suggest the need for antiinflammatory treatment.     

Time of appearance during development of differences in nigrostriatal tyrosine hydroxylase activity in two inbred mouse strains

The greater activity of tyrosine hydroxylase (TH) in substantia nigra and corpus striata of adult BALB/cJ than CBA/J mice, is attributable to differences in the number of dopamine neurons in the ventral midbrain tegmentum. To determine if strain differences in TH activity develop postnatally we have measured the development of TH in the midbrain (SN) and in the corpus striatum (CS). In the midbrain neonatal TH activity was 20% of adult levels. Thereafter, TH activity increased rapidly achieving adult levels by 11 days. A 25% "overshoot' above adult values at 15 days was followed by a gradual decrease to adult activity at 4 weeks. In the CS neonatal activity was about 10% of adult levels and increased slowly to reach adult values at 4 weeks. Striatal choline acetyltransferase (CAT) activity in the neonate was only 3.7% of adult values and at 21 days had only reached 70% of adult activity. Neonatal glutamic acid decarboxylase (GAD) activity was relatively high in both brain regions and increased gradually to adult activity by 4 weeks. Strain differences in TH activity were not present at birth but first appeared at 9 days in SN and 11 days in CS. Once established, the differences were maintained. These results suggest that strain differences in TH are most probably a consequence of differences in postnatal neuron survival, although the possibility that some neurons lose their phenotypic expression of TH cannot be excluded.     

Practices surrounding syringe acquisition and disposal: effects of Syringe Exchange Programmes from different Brazilian regions—the AjUDE-Brasil II Project

The study describes practices relating to syringe acquisition and disposal by Syringe Exchange Programme (SEP) participants. A cross-sectional multi-city study enrolled 857 injection drug users (IDUs) from six SEPs in different Brazilian regions, and assessed self-reported acquisition and disposal behaviours. Seven hundred and nine males (82.9%) and 146 females (17.1%) were recruited through outreach and interviewed, most from the streets or their neighbourhoods (54.1%). The average age was 28.5 years; 76.4% reported injecting cocaine in the past 6 months. Sources for acquiring new syringes differed significantly between time of injection drug use debut and the 6 months prior to interview. Fifty-three percent of IDUs reported acquiring their syringes in pharmacies when they initiated injection drug use, whereas most reported acquiring new syringes in the 6 months before interview from several simultaneous sources: 69% through SEPs; 58% through pharmacies; 36% from friends and/or sexual partners; and 17% from other health services. Across SEPs, acquisition and disposal varied widely. Most interviewees discarded their syringes on the streets, in open fields, or in the garbage or sewage. Restrictions on syringe availability and unsafe practices may be functioning as barriers to the public health recommendation of one-time use of sterile syringes for IDUs and discouraging community support to SEPs. Further increase in access to legal, inexpensive and timely sterile syringes, as well as counselling about the merits of one-time use and safer disposal must be reinforced as part of efforts to minimise high-risk behaviours and curb the spread of blood-borne infections.     

Accelerated flap prefabrication with vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) is a potent promoter of angiogenesis that has been shown to enhance revascularization of ischemic tissues, including skin flaps. This study was designed to investigate the value of a single topical application of recombinant human VEGF to accelerate flap viability in a rat model of a non-ischemic prefabricated flap. Prefabricated flaps were created in 48 Sprague-Dawley rats. An autologous tail artery loop was anastomosed to the femoral artery and vein, and implanted subcutaneously in the lower abdomen. Flaps were divided into two groups of 24 each. At the time of loop implantation the control group received 0.9 percent NaCl or a 16 percent vol/wet polyvinyl alcohol (PVA) solution: the treatment group received VEGF in 0.9 percent NaCl or VEGF in PVA. The PVA gel was used to facilitate topical application In each group, 3- x 4-cm flaps nurtured by the tail artery pedicle were elevated and resutured into place after 3, 4, and 5 weeks. The percentage of surviving skin of each flap was determined by planimetry 7 days after flap elevation. Mean skin survival areas at 3, 4, and 5 weeks were control group 0 percent. 8 percent and 17.5 percent; and VEGIF-treated group, 6 percent, 40 percent, and 66.7 percent respectively VEGF significantly improved flap survival by 5 weeks (p = 0.02). These results suggest that VEGF can accelerate maturation of prefabricated flaps. This approach could expand the application of flap prefabrication as a resource for reconstructive surgery.     

Acute cardiopulmonary alterations induced by fine particulate matter of S?o Paulo, Brazil.

The mechanisms involved in the association between air pollution and increased cardiovascular morbidity are not fully understood. The objective of this study was to test the hypothesis that fine particulate matter (PM(2.5)) induces systemic inflammation and vasoconstriction of small arteries in the lung and heart of rats. Thirty-eight healthy Wistar rats were anesthetized, intubated, and submitted to the instillation of 1 ml of distilled water diluted in the following solution: blank filter, 100 microg and 500 microg of PM(2.5). PM(2.5) was collected in glass fiber filters with a high-volume sampler. The animals were sacrificed 24 h after instillation when blood, heart, and lung samples were collected for morphological and wet-to-dry weight ratio analysis. PM(2.5) consisted of the following elements: sulphur, arsenic, bromine, chlorine, cobalt, iron, lanthanum, manganese, antimony, scandium, and thorium. Total reticulocytes significantly increased at both PM(2.5) doses (p < 0.05) while hematocrit levels increased in the 500 microg group (p < 0.05). Quantification of segmented neutrophils and fibrinogen levels showed a significant decrease, while lymphocytes counting increased with 100 microg of PM(2.5) (p < 0.05). A significant dose-dependent decrease of intra-acinar pulmonary arteriole lumen/wall ratio (L/W) was observed in PM groups (p < 0.001). Peribronchiolar arterioles L/W showed a significant decrease in the 500 microg group (p < 0.001). A significant increase in heart wet-to-dry weight ratio was observed in the 500 microg group (p < 0.001). In conclusion, fine environment particles in the city of S?o Paulo promote pulmonary and cardiac histological alterations. Pulmonary vasculature was markedly affected by particle instillation, resulting in significant vasoconstriction in healthy rats.     

Combining lung-protective strategies in experimental acute lung injury: The impact of high-frequency partial liquid ventilation.

OBJECTIVE: To evaluate the independent and combined effects of high-frequency oscillatory ventilation (HFOV) and partial liquid ventilation (PLV) on gas exchange, pulmonary histopathology, inflammation, and oxidative tissue damage in an animal model of acute lung injury. DESIGN: Prospective, randomized animal study. SETTING: Research laboratory of a health sciences university. SUBJECTS: Fifty New Zealand White rabbits. INTERVENTIONS: Juvenile rabbits injured by lipopolysaccharide infusion and saline lung lavage were assigned to conventional ventilation (CMV), PLV, HFOV, or high-frequency partial liquid ventilation (HF-PLV) with a full or half dose (HF-PLV1/2) of perfluorochemical (PFC). Uninjured ventilated animals served as controls. Arterial blood gases were obtained every 30 mins during the 4-hr study. Histopathologic evaluation was performed using a lung injury scoring system. Oxidative lung injury was assessed by measuring malondialdehyde and 4-hydroxynonenal in lung homogenates. MEASUREMENTS AND MAIN RESULTS: HFOV, PLV, or a combination of both methods (HF-PLV) resulted in significantly improved oxygenation, more favorable lung histopathology, reduced neutrophil infiltration, and attenuated oxidative damage compared with CMV. HF-PLV with a full PFC dose did not provide any additional benefit compared with HFOV alone. HF-PLV1/2 was associated with decreased pulmonary leukostasis compared with HF-PLV. CONCLUSIONS: The combination of HFOV and PLV (HF-PLV) does not provide any additional benefit compared with HFOV or PLV alone in a combined model of lung injury when lung recruitment and volume optimization can be achieved. The use of a lower PFC dose (HF-PLV1/2) is associated with decreased pulmonary leukostasis compared with HF-PLV and deserves further study.     

Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone

Orthostatic intolerance is the development of disabling symptoms upon assuming an upright posture that are relieved partially by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations because of excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurologic, and psychiatric evaluation, which usually fails to identify a specific abnormality. The authors investigated the autonomic and hemodynamic profile of patients with POTS and the effectiveness of bisoprolol and fludrocortisone. The authors evaluated 11 female patients with POTS before and after medical treatment with a cardioselective bisoprolol -blocker or fludrocortisone, or both, and 11 age-matched control patients. Variability of heart rate and systolic blood pressure was assessed by fast Fourier transform, and spontaneous baroreceptor gain was assessed by use of the temporal sequences slope and index. Modelflow was used to quantify hemodynamics. Symptoms in all patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol or fludrocortisone or both. These results need further confirmation in a controlled double-blind study. Proper medical treatment improves dramatically the clinical and autonomic-hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is the result of a hyperadrenergic activation or hypovolemia during orthostasis.     

Transdermal nitroglycerine enhances spinal neostigmine postoperative analgesia following gynecological surgery

BACKGROUND: Intrathecal neostigmine causes analgesia by inhibiting the breakdown of acetylcholine. Experimental data suggest that the production of endogenous nitric oxide is necessary for tonic cholinergic inhibition of spinal pain transmission. The purpose of this study was to determine whether association of transdermal nitroglycerine would enhance analgesia from a low dose of intrathecal neostigmine in patients undergoing gynecologic surgery during spinal anesthesia. METHODS: Forty-eight patients were randomized to one of four groups. Patients were premedicated with use of 0.05-0.1 mg/kg intravenous midazolam and received 15 mg bupivacaine plus 1 ml test drug intrathecally (saline or neostigmine, 5 microgram). Twenty to 30 min after the spinal puncture, a transdermal patch of either 5 mg nitroglycerin or placebo was applied. The control (Con) group received spinal saline and transdermal placebo. The neostigmine group received spinal neostigmine and transdermal placebo. The nitroglycerin group received spinal saline and a transdermal nitroglycerine patch. Finally, the neostigmine-nitroglycerin group received spinal neostigmine and transdermal nitroglycerine. Pain and adverse effects were evaluated using a 10-cm visual analog scale. RESULTS: Patients in the groups were similar regarding age, weight, height, and American Society of Anesthesiologists status. Sensory level to pin prick at 10 min, surgical duration, anesthetic duration, and visual analog scale score for pain at the time of administration of first rescue medication were statistically the same for all groups. The time to administration of first rescue analgesic (min) was longer in the neostigmine-nitroglycerin group (550 min; range, 458-1,440 min; median, 25-75th percentile) compared with the other groups (P < 0.001). The neostigmine-nitroglycerin group required fewer rescue analgesics in 24 h than did the control group (P < 0.0005), whereas the neostigmine group required less analgesics compared with the control group (P < 0.02). The incidence of perioperative adverse effects (nausea, vomiting, headache, back pain) was similar among groups (P > 0.05). CONCLUSION: Although neither intrathecal 5 microgram neostigmine alone nor transdermal nitroglycerine alone (5 mg/day) delayed the time to administration of first rescue analgesics, the combination of both provided an average of 14 h of effective postoperative analgesia after vaginoplasty, suggesting that transdermal nitroglycerin and the central cholinergic agent neostigmine may enhance each other's antinociceptive effects at the dose studied.     

Changes in social emotion recognition following traumatic frontal lobe injury

Changes in social and emotional behaviour have been consistently observed in patients with traumatic brain injury. These changes are associated with emotion recognition deficits which represent one of the major barriers to a successful familiar and social reintegration. In the present study, 32 patients with traumatic brain injury, involving the frontal lobe, and 41 ageand education-matched healthy controls were analyzed. A Go/No-Go task was designed, where each participant had to recognize faces representing three social emotions (arrogance, guilt and jealousy). Results suggested that ability to recognize two social emotions (arrogance and jealousy) was significantly reduced in patients with traumatic brain injury, indicating frontal lesion can reduce emotion recognition ability. In addition, the analysis of the results for hemispheric lesion location (right, left or bilateral) suggested the bilateral lesion sub-group showed a lower accuracy on all social emotions.