Effects of mycophenolate sodium on mucociliary clearance using a bronchial section and anastomosis rodent model.

OBJECTIVE: To study the effects of mycophenolate sodium on mucociliary clearance. INTRODUCTION: Mycophenolate is one of the most commonly used immunosuppressive drugs in lung transplantation. Although its pharmacokinetic properties are well defined, its side effects on mucociliary clearance have not yet been studied. METHODS: Sixty rats were subjected to left bronchial section and anastomosis. The right bronchus was used as a control. After surgery, the rats were assigned to two groups based on whether they received saline solution (n = 30) or mycophenolate sodium (n = 30). After 7, 15, or 30 days of treatment, 10 animals from each group were sacrificed, and in vitro mucus transportability, in situ mucociliary transport velocity and ciliary beat frequency were measured. RESULTS: The analysis of mucus transportability revealed that neither mycophenolate nor bronchial section altered any transportability related property for up to 30 days of treatment after surgery (p>0.05). With regard to ciliary beat frequency, the operated left bronchi from the mycophenolate group showed a significant decrease on post-surgical day 30 (p = 0.003). In addition, we found a significant reduction in the in situ mucociliary transport velocity in the mycophenolate-treated group (p = 0.0001). DISCUSSION: These data add important information regarding mucociliary clearance dysfunction following mycophenolate therapy and suggest that mycophenolate might contribute to the high incidence of respiratory tract infections in lung transplant patients. Further studies are needed to investigate the combined action of mycophenolate with other immunosuppressive drugs and to establish methods to protect and recover mucociliary clearance, an important airway defense mechanism.

Effects of mycophenolate sodium on mucociliary clearance using a bronchial section and anastomosis rodent model

OBJECTIVE: To study the effects of mycophenolate sodium on mucociliary clearance. INTRODUCTION: Mycophenolate is one of the most commonly used immunosuppressive drugs in lung transplantation. Although its pharmacokinetic properties are well defined, its side effects on mucociliary clearance have not yet been studied. METHODS: Sixty rats were subjected to left bronchial section and anastomosis. The right bronchus was used as a control. After surgery, the rats were assigned to two groups based on whether they received saline solution (n = 30) or mycophenolate sodium (n = 30). After 7, 15, or 30 days of treatment, 10 animals from each group were sacrificed, and in vitro mucus transportability, in situ mucociliary transport velocity and ciliary beat frequency were measured. RESULTS: The analysis of mucus transportability revealed that neither mycophenolate nor bronchial section altered any transportability related property for up to 30 days of treatment after surgery (p>0.05). With regard to ciliary beat frequency, the operated left bronchi from the mycophenolate group showed a significant decrease on post-surgical day 30 (p = 0.003). In addition, we found a significant reduction in the in situ mucociliary transport velocity in the mycophenolate-treated group (p = 0.0001). DISCUSSION: These data add important information regarding mucociliary clearance dysfunction following mycophenolate therapy and suggest that mycophenolate might contribute to the high incidence of respiratory tract infections in lung transplant patients. Further studies are needed to investigate the combined action of mycophenolate with other immunosuppressive drugs and to establish methods to protect and recover mucociliary clearance, an important airway defense mechanism.

Spatial analysis of egg distribution and geographic changes in the spawning habitat of the Brazilian sardine Sardinella brasiliensis.

This paper establishes the spawning habitat of the Brazilian sardine Sardinella brasiliensis and investigates the spatial variability of egg density and its relation with oceanographic conditions in the shelf of the south-east Brazil Bight (SBB). The spawning habitats of S. brasiliensis have been defined in terms of spatial models of egg density, temperature-salinity plots, quotient (Q) analysis and remote sensing data. Quotient curves (Q(C)) were constructed using the geographic distribution of egg density, temperature and salinity from samples collected during nine survey cruises between 1976 and 1993. The interannual sea surface temperature (SST) variability was determined using principal component analysis on the SST anomalies (SSTA) estimated from remote sensing data over the period between 1985 and 2007. The spatial pattern of egg occurrences in the SBB indicated that the largest concentration occurred between Paranaguá and São Sebastião. Spawning habitat expanded and contracted during the years, fluctuating around Paranaguá. In January 1978 and January 1993, eggs were found nearly everywhere along the inner shelf of the SBB, while in January 1988 and 1991 spawning had contracted to their southernmost position. The SSTA maps for the spawning periods showed that in the case of habitat expansion (1993 only) anomalies over the SBB were zero or slightly negative, whereas for the contraction period anomalies were all positive. Sardinella brasiliensis is capable of exploring suitable spawning sites provided by the entrainment of the colder and less-saline South Atlantic Central Water onto the shelf by means of both coastal wind-driven (to the north-east of the SBB) and meander-induced (to the south-west of the SBB) upwelling.

Efeitos do micofenolato de sódio no aparelho mucociliar: estudo experimental em ratos / Effects of mycophenolate on mucociliary clearance: experimental study in rats

O transplante pulmonar tem se tornado a opção de tratamento para os pacientes com doença pulmonar terminal. Maiores problemas associados são a rejeição e a infecção; por isso, a importância de se estudar os mecanismos de defesa do aparelho respiratório e o efeito de drogas imunossupressoras sobre o mesmo. O micofenolato de sódio é uma droga imunossupressora que inibe a proliferação dos linfócitos, envolvidos no mecanismo de defesa celular. Objetivo: Avaliar os efeitos do micofenolato de sódio versus solução salina no aparelho mucociliar de ratos. Métodos: Foram utilizados 60 ratos machos Wistar. Todos foram submetidos à cirurgia de secção e anastomose brônquica esquerda. Distribuídos aleatoriamente em dois grupos, um grupo de 30 ratos que recebeu solução salina, pulmão direito controle (S) e pulmão esquerdo operado (SC); enquanto que o segundo grupo recebeu, também por gavagem, micofenolato, pulmão direito controle (M) e pulmão esquerdo operado (MC); até o sacrifício no 7º, 15º e 30º dia de tratamento. Avaliados a frequência do batimento ciliar (FBC), velocidade do transporte mucociliar in vivo (VTMC); e a velocidade de transporte mucociliar in vitro (PLT). Resultados: A FBC é menor no grupo MC em relação ao grupo M, no período de 30 dias (p= 0, 003); e dentro do grupo MC, ao compararmos o 7º e o 30º (p=0, 0001) dia e o 15º e o 30º dia (p=0, 026) de tratamento notamos uma piora da FBC. Em relação à VTMC houve uma melhora no grupo SC no 7º e 30º dia (p=0, 003) e 15º e 30 º dia (p= 0, 005) de tratamento. Comparando o grupo SC e MC no período de 30 dias, verificamos que esta VTMC é menor no segundo grupo (p= 0, 0001). No PLT não houve diferença estatística entre os grupos. Conclusões: O micofenolato associado à secção brônquica diminui a FBC no decorrer do tempo; a VTMC no grupo que recebeu solução salina associado ao procedimento cirúrgico apresentou uma recuperação no decorrer do tempo, o mesmo não foi observado quando associado ao procedimento...

The lung transplantation has become the treatment option for the patients with terminal lung illness. Major problems associated are rejection and infection; that´s the reason the importance of studying the mechanism of respiratory system defense and the immunosuppressive drugs effects about itself. The sodium Mycophenolate is an immunosuppressive drug that inhibits the proliferation of lymphocytes, involved in cellular defense mechanism. Purpose: evaluating the sodium Mycophenolate effects versus salt solution in the mucociliary system of rats. Methods: sixty male Wistar rats were used. Every rat was submitted to section surgery and left bronchial anastomosis. The rats were randomly divided: a group of 30 rats which received saline solution; Right lung control (S) and operated Left lung (SC); meanwhile the second group received also by gavage Mycophenolate, Right lung control (M) and Left operated lung (MC); until the sacrifice at the seventh, fifteenth and thirtieth day of treatment. Ciliary beat frequency (CBF) has been evaluated, mucociliary transport speed in vivo (MCTS); and the Velocity of Transport of the Mucociliary in vitro (PLT). Results: the CBF is smaller in the MC group than M group, in thirty days (p=0,003), and inside MC group, when comparing with the seventh and the thirtieth (p=0, 0001) day and the fifteenth and the thirtieth day (p= 0,026) of the treatment we noticed a worsening of CBF. About the MCTS there was an improvement in the SC group in the seventh and the thirtieth day (p=0,003) and the seventh and the thirtieth day (p=0,005) of treatment. The comparing the SC and the MC groups in thirty days we noticed that this MCTS is smaller in the second group (p=0, 0001). In the PLT there were no statistic differences between those groups. Conclusions: the Mycophenolate associated to bronchial section reduces the CBF over time; the MCTS in the group that received salt solution associated to surgical procedure showed recovery, the same...

Febre reumática: um modelo animal para uma vacina humana / Rheumatic fever: an animal model for a human disease

Avaliamos o papel da proteína M na indução de lesões similares às observadas na febre reumática (FR), utilizando o rato Lewis como modelo experimental. Identificamos a cepa M1 do S. pyogenes como a mais freqüentemente isolada em amostras locais. Produzimos a proteína M1 recombinante e, mostramos que a imunização usando esta proteína produziu lesões similares às lesões patognomônicas da FR em 50 por cento dos animais. Demonstramos resposta humoral e celular específica contra a proteína M1 e contra as regiões M1AB e M1C. Não observamos, entretanto, reações cruzadas com a miosina cardíaca. Células mononucleares infiltrantes do miocárdio de animais imunizados foram cultivadas, em presença de IL-2, mostrando que estas células foram sensibilizadas. Em conclusão, o modelo proposto ajudará a esclarecer a imunopatologia da FR...

We have evaluated M protein role in eliciting rheumatic fever-like lesions, using the Lewis rat as an animal model. We have identified S. pyogenes M1 strain as the most frequently isolated from local samples. We have produced M1 recombinant protein and shown that immunization using this protein led to rheumatic fever characteristic lesions in 50 per cent of the animals. We demonstrated a humoral and cellular specific response targeting M1 protein and M1AB and M1C regions. We did not observe, however, cross reactions with cardiac myosin. Mononuclear cells infiltrating myocardium of immunized animals were grown in presence of IL-2, showing that these cells were sensitized. In conclusion, the proposed model will help clarifying on the...

Isolation and isoenzyme characterization of Leishmania (Viannia) braziliensis from a case of human cutaneous leishmaniasis in northeast centre of the state of São Paulo

The diagnosis of human cutaneous leishmaniasis in small towns is sometimes made without the species identification of the Leishmania, even in areas without previous epidemiological surveys. Here we report the isolation of a Leishmania strain from a patient of Rincão, state of São Paulo, that was identified by isoenzyme characterization as L. (Viannia) braziliensis. Sand fly collections were made in the area where the patient live in order to investigate the likely vector species.

Isolation and isoenzyme characterization of Leishmania (Viannia) braziliensis from a case of human cutaneous leishmaniasis in northeast centre of the state of São Paulo.

The diagnosis of human cutaneous leishmaniasis in small towns is sometimes made without the species identification of the Leishmania, even in areas without previous epidemiological surveys. Here we report the isolation of a Leishmania strain from a patient of Rincão, state of São Paulo, that was identified by isoenzyme characterization as L. (Viannia) braziliensis. Sand fly collections were made in the area where the patient live in order to investigate the likely vector species.

Paradoxical embolism and aortic occlusion: a case report.

This is the case report of a 45-year-old woman who sustained a left popliteal artery embolism. Ten days after popliteal embolectomy, she developed sudden occlusion of the distal aorta. She required a bifemoral embolectomy. Transesophageal echocardiogram demonstrated an atrial septal aneurysm and a septal defect with a right to left shunt. A venogram showed deep venous thrombosis in the right leg as the potential source of the embolism. Paradoxical embolization should be considered when ever an unexplained arterial occlusion occurs, especially in younger patients.

Indication for surgery of asymptomatic carotid lesions.

The incidence of cerebrovascular diseases with transient or persistent neurologic dysfunction has increased significantly. Although patients with symptomatic carotid artery stenosis clearly benefit from operative therapy, the indication to prophylactic surgery of asymptomatic carotid lesions however is still controversial. Based on data from a recently completed prospective randomized study and on analysis of the literature the indication and results of surgical treatment of asymptomatic stenoses of the carotid arteries are discussed. From 1970 to 1990 a total of 744 uni-or bilateral reconstructions of the internal carotid artery were performed in 631 patients. The perioperative morbidity (permanent neurologic deficiency) and mortality was 1.1% (n = 8) resp. 0.8% (n = 6). During the follow up period up to 18 years another 9 patients suffered from stroke (1.2%). The annual stroke incidence amounted to 0.2%. An important prerequisite for surgery is the so called critical internal carotid artery stenosis, implying reduced cerebral vasomotor reactivity or high embolic risk of an ulcerative plaque. Proper selection of patients (exclusion of multiple concomitant diseases) and an experienced team of vascular surgeons with operative morbidity and mortality below 1-2% validates surgical treatment of asymptomatic carotid artery stenoses.

Extraanatomic bypass-prolongation after aorto-respectively ilio-femoral inflow repair.

Redo-operations in patients with a persistent or recurrent vascular insufficiency following a triad procedure (aorto-iliac inflow repair, profundaplasty and lumbar sympathectomy) may bring on problems from re-exposure of the groin with an increased risk of wound healing complications. A new technique for bypass-prolongation, i.e.g., an extraanatomic iliopopliteal bypass (group A: n = 16) is presented as an alternative to the conventional femoro-popliteal bypass prolongation (group B: n = 55). In both groups the effect of revascularisation was sufficient and comparable for definitive healing of distal ischemic lesions in more than 85%. The cumulative patency rate in both collectives after 1 and 5 years did not differ. Group A: 82 respectively 64% versus 75.6 respectively 59.5% in group B. However, the number of redo-operations could be significantly (p less than 0.05) reduced to 12.5% (n = 2) in group A, compared with 21.8% (n = 12) in case of an anatomical bypass-prolongation (group B). There were no wound healing complications in the groin after extranatomical reconstruction, compared with 5 after femoro-popliteal prolongation. The main advantage of this new approach, is 1. avoidance of a difficult femoral redissection in the groin with reduced risk of wound infection, 2. easy extraperitoneal exposure of the prosthetic limb at iliac level and 3. optimal healing in of the graft (ePTFE with external ringsupport). Since a significant reduction of wound healing complications could be achieved, the presented technique therefore is regarded as a superior alternative to the anatomical femoropopliteal bypass prolongation.

[Infrarenal aortic aneurysm in Behçet's disease. Case report and review of the literature]. / Infrarenales Aortenaneurysma bei Morbus Behçet. Fallbericht und Literaturübersicht.

A 55-year old Turkish male was admitted with a staged aortic rupture requiring emergent surgical resection of the infrarenal aorta. Anamnesis and typical clinical findings (aphthosis, genital ulcers, pustulosis, arthritis) allowed the postoperative diagnosis of Behçet's disease. This etiologically unclear disease rarely occurs in patients from western European countries. Main symptoms are concerning the skin, the mucous membranes, and the eyes. The vascular system may occasionally be involved. In patients presenting with inflammatory arterial aneurysms, arterial or venous occlusions, careful search for the main symptoms will provide adequate diagnosis. Acute arterial affections, especially aneurysms, often urge surgical treatment. Until now, there is no effective medical prophylaxis.

[Lumbar spinal nerve root compression syndrome as an atypical initial manifestation of a rare vascular disease]. / Lumbales Wurzelkompressionssyndrom als atypische Erstmanifestation einer seltenen Gefässerkrankung.

A 55 year old male Turkish patient developed L3/L4 root compression caused by a retroperitoneal hematoma after covered perforation of the infrarenal aorta. The aneurysm was resected and a tube interposition made. For more than 20 years the patient has suffered from oral and scrotal ulcers. These signs led to the diagnosis of Behçet's disease. A review of the literature revealed 200 arterial complications (aneurysms and occlusions) in 105 patients with Behçet's disease, only 19 of them had aneurysms of the infrarenal aorta.

[Arterial lesions following radiotherapy]. / Arterielle Gefässschäden nach Strahlentherapie.

From 1980 to 1990 twelve patients with vascular lesions attributable to irradiation were treated. The time interval between radiotherapy because of malignancy and onset of symptoms due to radiation-induced atherosclerosis was on an average 7 years (1 month-29 years). A typical morphological finding at angiography was the well-localised vascular lesion in the previous radiation area, its localisation clearly distinguishable from typical atherosclerotic lesions. 10 patients had other radiation damage with involvement of the skin and perivascular tissue frequently necessitating an extra-anatomic reconstruction (n = 6). 4 patients had an anatomical reconstruction, one had a PTA, one was treated conservatively. Due to absence of multifocal arteriosclerotic lesions, long-term results of vascular reconstruction are good and will certainly contribute to further improvement of life quality after curative therapy for malignant disease.

Aneurysma transformation in congenital venous angiodysplasias in lower extremities.

Based on a retrospective evaluation of 107 patients with congenital venous angiodysplasia of the Type Klippel-Trenaunay (n = 76) and Type Servelle-Martorell (n = 31) the frequency and pathogenesis of aneurysma formation in the venous system has been analysed. The vascular patterns include both cylindric ectasia and fusiform aneurysms with an incidence of approximately 40%. Preferred locations are subcutaneous drainage veins, the popliteal, external iliac vein and atypic communicating veins between the superficial and the deep venous system. Complications of the aneurysm such as local thrombosis, recurrent pulmonary embolism or bleeding from ruptur were not observed. The aneurysma formation in venous angiodysplasias results probably from the causative factors: congenital weakness of the venous wall and an abnormal hemodynamical stress situation. The latter is caused by concomitant malformations of the deep venous system. The persistent intermittent venous hypertension associated with a more or less pronounced increase of the venous volume in the affected venous system of the limb results in a deep venous insufficiency respectively venous reflux disease. The therapy of choice is predominantly conservative, i.e., external compression bandages or stockings to reduce the deleterious effects of a chronic deep venous insufficiency respectively venous reflux disease. Surgery is indicated under two conditions: a) in the presence of aneurysm complications or b) for the elimination of a pathological short circuit flow in some drainage veins. Antireflux surgery, i.e., venous valve transfer from the brachial vein, is up to recently still in a stage of experimental-clinical investigation.

[Congenital angiodysplasia of the limbs; diagnosis and therapy]. / Congenitale angiodysplasie van de ledematen; diagnose en therapie.

A complete check-up of vascular morphology and haemodynamics in patients resulted in a differentiation of three clinical entities: (I) type F. P. Weber: multiple active arteriovenous fistulas inducing overgrowth of the skeleton, (2) type Klippel-Trenaunay: venous angiodysplasia with the triad localized gigantism, varicose veins, naevus flammeus, (3) type Servelle-Martorell: systemic haemangiomatosis including the bone and soft tissues resulting in hypoplasia of the skeleton. Early diagnosis and differentiation of these different clinical types are needed for the assessment of the spontaneous course of the disease and choice of an optimal therapeutical approach. In the presence of active arteriovenous fistula (type F. P. Weber) the therapeutic principle should be focused on the normalisation of the shunt volume by surgery (skeletonisation) or catheter embolisation. In patients with venous angiodysplasias (type Klippel-Trenaunay or Servelle-Martorell) the therapy is aimed at prevention or reduction of deep venous insufficiency and is basically conservative by external compression bandages.

[Late vascular damage after unilateral leg amputation]. / Vaskulärer Spätschaden nach unilateraler Beinamputation.

The higher incidence of infrarenal aortic aneurysms in war-veterans with above knee amputations indicates that leg amputation besides arteriosclerotic risk factors constitutes a relevant pathogenetic factor for the late development of an abdominal aortic aneurysm. A retrospective study of 25 mainly young patients with above knee amputation showed that already one year after leg-loss a typical adaptive narrowing of the pelvic and leg arteries with significant reduction of the flow volume of 37% on the amputated side could be registered. Unilateral flow reduction resp. interruption causes an asymmetric flow pattern at the aortic bifurcation. The changed hemodynamics are probably the main cause for late damage to the aorto-iliac vessels. The clinical importance of these results is that patients with unilateral leg amputation should have regular follow up investigation in order to detect late sequelae on the aorto-iliac vessels and to perform elective surgery for abdominal aortic aneurysm. Ipsilateral occlusive arterial disease as well as abdominal aortic aneurysms must be regarded as secondary late damage after leg amputation justifying obligatory indemnification.

Aortic aneurysms as late sequelae of above-knee amputation.

The infrarenal aorta was examined by ultrasound in 329 men who had lost a leg in World War II and in 702 war veterans. The groups were similar in terms of age and risk factors for arteriosclerosis. Abdominal aortic aneurysms were found in 5.8% of the amputees compared with 1.1% of the non-amputees. Unilateral flow reduction after leg amputation causes an asymmetrical flow pattern at the aortic bifurcation, and this is probably the main cause of late damage to the aorta.