Anandamide injected into the lateral ventricle of the brain inhibits submandibular salivary secretion by attenuating parasympathetic neurotransmission

Our objective was to determine the effect of arachidonylethanolamide (anandamide, AEA) injected intracerebroventricularly (icv) into the lateral ventricle of the rat brain on submandibular gland (SMG) salivary secretion. Parasympathetic decentralization (PSD) produced by cutting the chorda tympani nerve strongly inhibited methacholine (MC)-induced salivary secretion while sympathetic denervation (SD) produced by removing the superior cervical ganglia reduced it slightly. Also, AEA (50 ng/5 µL, icv) significantly decreased MC-induced salivary secretion in intact rats (MC 1 µg/kg: control (C), 5.3 ± 0.6 vs AEA, 2.7 ± 0.6 mg; MC 3 µg/kg: C, 17.6 ± 1.0 vs AEA, 8.7 ± 0.9 mg; MC 10 µg/kg: C, 37.4 ± 1.2 vs AEA, 22.9 ± 2.6 mg). However, AEA did not alter the significantly reduced salivary secretion in rats with PSD, but decreased the slightly reduced salivary secretion in rats with SD (MC 1 µg/kg: C, 3.8 ± 0.8 vs AEA, 1.4 ± 0.6 mg; MC 3 µg/kg: C, 14.7 ± 2.4 vs AEA, 6.9 ± 1.2 mg; P < 0.05; MC 10 µg/kg: C, 39.5 ± 1.0 vs AEA, 22.3 ± 0.5 mg; P < 0.001). We showed that the inhibitory effect of AEA is mediated by cannabinoid type 1 CB1 receptors and involves GABAergic neurotransmission, since it was blocked by previous injection of the CB1 receptor antagonist AM251 (500 ng/5 µL, icv) or of the GABA A receptor antagonist, bicuculline (25 ng/5 µL, icv). Our results suggest that parasympathetic neurotransmission from the central nervous system to the SMG can be inhibited by endocannabinoid and GABAergic systems.

Functional evidence that the central renin-angiotensin system plays a role in the pressor response induced by central injection of carbachol

We investigated the effects of losartan, an AT1-receptor blocker, and ramipril, a converting enzyme inhibitor, on the pressor response induced by angiotensin II (ANG II) and carbachol (a cholinergic receptor agonist). Male Holtzman rats (250-300 g) with a stainless steel cannula implanted into the lateral ventricle (LV) were used. The injection of losartan (50 nmol/1 &micro;l) into the LV blocked the pressor response induced by ANG II (12 ng/1 &micro;l) and carbachol (2 nmol/1 &micro;l). After injection of ANG II and carbachol into the LV, mean arterial pressure (MAP) increased to 31 &plusmn; 1 and 28 &plusmn; 2 mmHg, respectively. Previous injection of losartan abolished the increase in MAP induced by ANG II and carbachol into the LV (2 &plusmn; 1 and 5 &plusmn; 2 mmHg, respectively). The injection of ramipril (12 ng/1 &micro;l) prior to carbachol blocked the pressor effect of carbachol to 7 &plusmn; 3 mmHg. These results suggest an interaction between central cholinergic pathways and the angiotensinergic system in the regulation of arterial blood pressure

Effect of injection of L-NAME on drinking response

The drinking behavior responses to centrally administered NG-nitro-L-arginine methyl ester (L-NAME; 10, 20 or 40 µg/µl), an inhibitor of nitric oxide synthase, were studied in satiated rats, with cannulae stereotaxically implanted into the lateral ventricle (LV) and subfornical organ (SFO). Water intake increased in all animals after angiotensin II (ANG II) injection into the LV, with values of 14.2 ± 1.4 ml/h. After injection of L-NAME at doses of 10, 20 or 40 µg/µl into the SFO before injection of ANG II (12 ng/µl) into the LV, water intake decreased progressively and reached basal levels after treatment with 0.15 M NaCl and with the highest dose of L-NAME (i.e., 40 µg). The water intake obtained after 40 µg/µl L-NAME was 0.8 ± 0.01 ml/h. Also, the injection of L-NAME, 10, 20 or 40 µg/µl, into the LV progressively reduced the water intake induced by hypertonic saline, with values of 5.3 ± 0.8, 3.2 ± 0.8 and 0.7 ± 0.01 ml/h, respectively. These results indicate that nitric oxide is involved in the regulation of drinking behavior induced by centrally administered ANG II and cellular dehydration and that the nitric oxide of the SFO plays an important role in this regulation.

Antidipsogenic effects of central adenosine-5'-triphosphate

Besides other physiological functions, adenosine-5'-triphosphate (ATP) is also a neurotransmitter that acts on purinergic receptors. In spite of the presence of purinergic receptors in forebrain areas involved with fluid-electrolyte balance, the effect of ATP on water intake has not been investigated. Therefore, we studied the effects of intracerebroventricular (icv) injections of ATP (100, 200 and 300 nmol/µL) alone or combined with DPCPX or PPADS (P1 and P2 purinergic antagonists, respectively, 25 nmol/µL) on water intake induced by water deprivation. In addition, the effect of icv ATP was also tested on water intake induced by intragastric load of 12% NaCl (2 mL/rat), acute treatment with the diuretic/natriuretic furosemide (20 mg/kg), icv angiotensin II (50 ng/µL) or icv carbachol (a cholinergic agonist, 4 nmol/µL), on sodium depletion-induced 1.8% NaCl intake, and on food intake induced by food deprivation. Male Holtzman rats (280-320 g, N = 7-11) had cannulas implanted into the lateral ventricle. Icv ATP (300 nmol/µL) reduced water intake induced by water deprivation (13.1 ± 1.9 vs saline: 19.0 ± 1.4 mL/2 h; P < 0.05), an effect blocked by pre-treatment with PPADS, but not DPCPX. Icv ATP also reduced water intake induced by NaCl intragastric load (5.6 ± 0.9 vs saline: 10.3 ± 1.4 mL/2 h; P < 0.05), acute furosemide treatment (0.5 ± 0.2 vs saline: 2.3 ± 0.6 mL/15 min; P < 0.05), and icv angiotensin II (2.2 ± 0.8 vs saline: 10.4 ± 2.0 mL/2 h; P < 0.05), without changing icv carbachol-induced water intake, sodium depletion-induced 1.8% NaCl intake and food deprivation-induced food intake. These data suggest that central ATP, acting on purinergic P2 receptors, reduces water intake induced by intracellular and extracellular dehydration.

Short-term follow-up of patients after aneurysmectomy of the left ventricle

OBJECTIVE: Left ventricular aneurysm is a complication of myocardial infarction that can best be treated by reconstructive surgeries that can restore ventricular geometry. We analyzed immediate results in a group of consecutive patients who underwent surgical correction of left ventricular aneurysms. METHODS: From January '90 to August '99, 94 patients - mean age 58.4 (ranging from 36 to 73 years), 65 (69.1%) males and 9 ( 30.8%) females - were operated upon. Pre-operative ejection fraction ranged from 0.22 to 0.58 (mean = 0.52), and the aneurysm was located in the antero-lateral area in 90.4% of the cases. Functional class III and IV (NYHA) was present in 82 (87.2%) patients, and 12 (12.7%) were in functional class I and II. Congestive heart failure was the most frequent cause (77.6%), occurring in isolation in 24.4% or associated with coronary artery diseases in 53.2%. RESULTS: Short-term follow-up showed a 7.4% mortality, and low cardiac output was the main cause of death. Coming off pump was uneventful in 73 patients (77.6%), with a 3.2% mortality and with the use of inotropics in 20 (21.3%). One patient (1%) did not come off the pump. CONCLUSION: Surgical correction was adequate in the immediate follow-up of operated patients, and mortality was higher in patients with higher functional class.

Mitral Valve Replacement and Remodeling of the Left Ventricle in Dilated Cardiomyopathy with Mitral Regurgitation: Initial Results

OBJECTIVE: This study evaluated the effects of a new method of mitral valve replacement on left ventricular (LV) remodeling and heart failure functional class. METHODS: Eight patients (6 men) with severe mitral regurgitation from end-stage dilated cardiomyopathy underwent surgery. Five patients were in functional class (FC) IV, 2 were in FC III and 1 was in FC III/IV. Age ranged from 33 to 63 years. Both the anterior and posterior leaflets of the mitral valve were divided into hemileaflets. The resultant 4 pedicles were displaced under traction toward the left atrium and anchored between the mitral annulus and an implanted valvular prosthesis. The beating heart facilitated ideal chordae tendineae positioning. RESULTS: All patients survived and were discharged from the hospital. After a mean follow-up period of 6.5 months (1-12 m), 5 patients were in FC I; 2 in FC I/II; and 1 in FC II. The preoperative ejection fraction ranged from 19% to 30% (mean: 25.7±3.4 %), and the postoperative ejection fraction ranged from 21% to 40% (mean: 31.1± 5.8%). Doppler echocardiography showed evidence of LV remodeling in 4 patients, including lateral wall changes and a tendency of the LV cavity to return to its elliptical shape. CONCLUSION: This technique of mitral valve replacement, involving new positioning of the chordae tendineae, allowed LV remodeling and improvement in FC during this brief follow-up period.

Aplicação de toxina botulínica tipo A para reduzir a saliva em pacientes com esclerose lateral amiotrófica

OBJETIVO: Demonstrar o efeito da aplicação local Botox® em glândulas salivares de pacientes com diagnóstico de esclerose lateral amiotrófica (ELA), seguindo nosso protocolo institucional de tratamento da sialorréia de 2002. FORMA DE ESTUDO: Clínico prospectivo. MATERIAL E MÉTODO: Cinco pacientes com ELA avaliados na Clínica de Otorrinolaringologia da AACD (Associação de Assistência à Criança Deficiente) foram submetidos à aplicação tópica de Botox® nas glândulas salivares e acompanhados por um ano. O protocolo consiste num questionário clínico sobre as habilidades de deglutir saliva e as repercussões na qualidade de vida. Os pacientes deveriam ter tratamento odontológico prévio, intolerância aos efeitos adversos dos anti-colinérgicos, e ausência de aplicação de. Botox® em outros sítios por pelo menos seis meses. A aplicação foi guiada por ultra-sonografia para as glândulas submandibulares e a dose administrada foi de 30U em um ponto, e 20U em cada glândula parótida distribuída em dois pontos, após anestesia tópica com prilocaína. RESULTADOS: Cinco pacientes com ELA, com idade entre 45 e 59 anos foram submetidos ao tratamento de redução de saliva pela aplicação de Botox® em glândulas salivares. Nós observamos que os sintomas de sialorréia melhoraram dramaticamente em quatro pacientes. Três pacientes permaneceram quatro meses sem queixas, com acentuada melhora na qualidade de vida. Nenhum paciente apresentou efeitos colaterais locais ou sistêmicos com a aplicação de Botox® em glândulas salivares. Nós observamos que os sintomas de sialorréia melhoraram dramaticamente em quatro pacientes. Três pacientes permaneceram quatro meses sem queixas, com acentuada melhora na qualidade de vida. Nenhum paciente apresentou efeitos colaterais locais ou sistêmicos com a aplicação de Botox® em glândulas salivares.

Estudo comparativo de pacientes submetidos à cauterização submucosa com ou sem fratura lateral do corneto inferior

OBJETIVO: Comparar os efeitos da cauterização submucosa do corneto inferior com e sem a fratura lateral. FORMA DE ESTUDO: Clínico prospectivo. MATERIAIS E MÉTODOS: Foram selecionados 20 pacientes aleatoriamente com diagnóstico de hipertrofia crônica dos cornetos nasais, e divididos em dois grupos. O primeiro foi submetido à cauterização submucosa com fratura lateral do corneto, e o segundo sem a fratura. Foram avaliados cinco quesitos, comparando-se os dois métodos: dor, sangramento nasal, cicatrização, formação de crostas e perviedade nasal. O seguimento pós-operatório foi realizado no 1º, 7º, 14º e 30º dias. RESULTADOS: Quanto à dor, sangramento nasal e formação de crostas o resultado foi semelhante para ambos os grupos. Em relação à cicatrização, houve melhores resultados no grupo submetido à fratura lateral nas primeiras duas semanas do seguimento. Quanto à perviedade nasal, 80% dos pacientes submetidos à cauterização submucosa com a fratura lateral referiram boa perviedade. Por outro lado, 30% dos pacientes não submetidos à fratura lateral relataram boa perviedade. CONCLUSÃO: A realização da cauterização submucosa do corneto inferior associada à fratura lateral é mais eficaz que a realização da cauterização isoladamente.

LATERAL FLOW ASSAY FOR CRYPTOCOCCAL ANTIGEN: AN IMPORTANT ADVANCE TO IMPROVE THE CONTINUUM OF HIV CARE AND REDUCE CRYPTOCOCCAL MENINGITIS-RELATED MORTALITY

SUMMARYAIDS-related cryptococcal meningitis continues to cause a substantial burden of death in low and middle income countries. The diagnostic use for detection of cryptococcal capsular polysaccharide antigen (CrAg) in serum and cerebrospinal fluid by latex agglutination test (CrAg-latex) or enzyme-linked immunoassay (EIA) has been available for over decades. Better diagnostics in asymptomatic and symptomatic phases of cryptococcosis are key components to reduce mortality. Recently, the cryptococcal antigen lateral flow assay (CrAg LFA) was included in the armamentarium for diagnosis. Unlike the other tests, the CrAg LFA is a dipstick immunochromatographic assay, in a format similar to the home pregnancy test, and requires little or no lab infrastructure. This test meets all of the World Health Organization ASSURED criteria (Affordable, Sensitive, Specific, User friendly, Rapid/robust, Equipment-free, and Delivered). CrAg LFA in serum, plasma, whole blood, or cerebrospinal fluid is useful for the diagnosis of disease caused by Cryptococcusspecies. The CrAg LFA has better analytical sensitivity for C. gattii than CrAg-latex or EIA. Prevention of cryptococcal disease is new application of CrAg LFA via screening of blood for subclinical infection in asymptomatic HIV-infected persons with CD4 counts < 100 cells/mL who are not receiving effective antiretroviral therapy. CrAg screening of leftover plasma specimens after CD4 testing can identify persons with asymptomatic infection who urgently require pre-emptive fluconazole, who will otherwise progress to symptomatic infection and/or die.

Persistence of the embryonic lateral marginal vein: report of two cases

PURPOSE: Congenital venous malformations of the lower limbs represent a particular challenge for the vascular surgeon. Persistence of fetal veins is a rare malformation, and the most common is the persistence of the lateral marginal vein usually observed in patients with Klippel-Trenaunnay Syndrome. The persistence of this embryonic vein as an isolated venous malformation without the other characteristics of the Klippel-Trenaunnay Syndrome has not yet been reported. This paper describes two cases. METHODS: Two patients, a 17-year-old male patient and a 16-year-old female, have had since their birth a large venous trunk in the lateral aspect of the right leg and thigh. The limbs underwent duplex scanning and phlebography. The surgical removal of the lateral marginal vein was performed. RESULTS: Surgical treatment resulted in very good functional and aesthetic results. Follow-up at 26 months showed no evidence of varicose vein recurrence. CONCLUSIONS: To achieve good results, surgical intervention may be indicated in cases of orthopedic deformity, hemorrhage, symptomatic, and unaesthetic lesions.

Myocardial perfusion by contrast echocardiography. Establishment of normal pattern of intracoronary injection and safety in humans

OBJECTIVE: To establish the normal pattern and safety of echocardiographic contrast in patients with no significant obstruction of epicardial coronary arteries. METHODS: 67 patients with normal coronary arteries or obstructions < 50% were selected from 277 patients who underwent coronary angiography (CA). Mean age was 56 ± 11years and 36 were males. At the end CA, echocardiographic contrast was selectively injected into each coronary artery. The parasternal short axis of the left ventricle (LV) was divided into six segments: anterior (A), antero-lateral (AL), postero-lateral (PL), posterior (P), infero-septal (IS) and antero-septal (AS). Anterolateral (ALPM) and posteromedial papillary muscles (PMPM) were also considered. The pattern and intensity of the appearance of the myocardial contrast was visually analyzed. RESULTS: The right coronary artery (RCA) was dominant in 60 patients. Contrast appearance was sudden and simultaneous in the 3 muscle layers. All segments could be contrasted after the injection in both coronary arteries. 100% of the AS, A and AL segments, 97% of the PL and 98% of the ALPM were perfused by the left coronary artery (LCA). P and IS segments were perfused by the RCA in 85% and 82%, respectively, and by a dominant LCA in 71% of the cases. The PMPM was perfused by a dominant RCA in 77% and by a dominant LCA in 86%. There were no symptoms. CONCLUSION: Intracoronary injection of the sonicated solution is a safe procedure that allows for an excellent opacification of the myocardium and can potentially be used during routine CA.

Double outlet right ventricle with anterior and left-sided aorta and subpulmonary ventricular septal defect

Double outlet right ventricle (DORV) is a heterogeneous group of abnormal ventriculoarterial connections where, by definition, both great arteries (pulmonary artery and aorta) arise primarily from the morphologically right ventricle. This condition affects 1-1.5% of the patients with congenital heart diseases, with a frequency of 1 in each 10,000 live births. We report the case of an 18-day-old infant with DORV and extremely rare anatomical features, such as anterior and left-sided aorta and subpulmonary ventricular septal defect (VSD). In addition to the anatomic features, the role of the echocardiogram for guiding the diagnosis and the surgical therapy of this congenital heart disease are discussed.