Collateral methotrexate resistance in cisplatin-selected murine leukemia cells

Resistance to anticancer drugs is a major cause of failure of many therapeutic protocols. A variety of mechanisms have been proposed to explain this phenomenon. The exact mechanism depends upon the drug of interest as well as the tumor type treated. While studying a cell line selected for its resistance to cisplatin we noted that the cells expressed a >25,000-fold collateral resistance to methotrexate. Given the magnitude of this resistance we elected to investigate this intriguing collateral resistance. From a series of investigations we have identified an alteration in a membrane protein of the resistant cell as compared to the sensitive cells that could be the primary mechanism of resistance. Our studies reviewed here indicate decreased tyrosine phosphorylation of a protein (molecular mass = 66) in the resistant cells, which results in little or no transfer of methotrexate from the medium into the cell. Since this is a relatively novel function for tyrosine phosphorylation, this information may provide insight into possible pharmacological approaches to modify therapeutic regimens by analyzing the status of this protein in tumor samples for a better survival of the cancer patients.

Mediastinal and pulmonary entomophthoromycosis with superior vena cava syndrome: case report

The first case of mediastinal and pulmonary entomophthoromycosis with supe rior vena cava syndrome is reported. The patient presented with a history of edema of the face, neck and upper limbs as well as collateral circulation in the anterior wall of the chest. Histological examination of tissue from mediastinum revealed a granulomatous reaction with microabscesses surrounded by eosinophilic amorphous material and with broad hyphae in the center. Culture was not performed because a preliminary diagnosis of nonHodgkin's malignant lymphoma was made. Surgical correction of the obstructed area was performed and the patient was sucessfully treated with potassium iodide. The authors propose that mediastinal entomoph thoromycosis must be considered in the differential diagnosis of diseases causing superior vena cava syndrome in tropical and sub-tropical regions. This case enlarges the spectrum of clinical manifestations of the zigomycosis caused by Entomoph-thoraceae.

Transradial approach for coronary interventions

OBJECTIVE: To assess the feasibility and safety of coronary interventions performed through the radial artery. METHODS: We studied 103 patients with ages from 38 to 86 years (57±8.7), 90 (87%) males, and: radial pulse with a good amplitude, presence of ulnar pulse, a good collateral flow through the palmar arch assessed with the Allen's test. RESULTS: The vascular approach was obtained in 97 (94%) patients, 88 (91%) treated electively and 9 (9%) during acute myocardial infarction, for primary angioplasty; 56 (64%) unstable angina; 22 (25%) stable angina; 10 (11%) were asymptomatic, 6 referred for recanalization of chronic occlusion and 4 silent ischemia in the first week after acute myocardial infarction. We approached 107 arteries: anterior descending artery, 49 (46%); right coronary artery, 27 (25%); circumflex artery, 25 (23%); diagonal artery, 6 (6%); and 2 saphenous vein bypass grafts. We treated 129 lesions: 80 (62%) B2 type; 23 (18%) B1 type; 17 (13%) C type; and 9 (7%). A type. There were 70 stents , and 59 balloon angioplasties performed. Thirty-two (33%) patients used GP IIb/IIIa inhibitors. The mean duration of the elective procedure was 42.3±12.8 min. Success, correct stent deployment and residual lesion <20%, was reached in 100% of the lesions treated with stent implantation; arterial dilation with residual lesion <50% was obtained in 96% of the lesions treated with transluminal coronary angioplasty (TCA). Complications, were: 1 (1.0%) non-Q-wave acute myocardial infarction; 2 (2%) hematomas in the forearm; and 2 losses of radial pulse. CONCLUSION: Radial artery aproach is practical and safe for percutaneous coronary interventions there was a low incidence of complications.

A New Use for the Amplatzer Duct Occluder Device

We report a case in which the Amplatzer device for percutaneous occlusion of ductus arteriosus was successfully used for occluding a large systemic-pulmonary collateral vessel in a patient who had previously undergone surgery for correction of pulmonary atresia and ventricular septal defect (Rastelli technique), and was awaiting the change of a cardiac tube. In the first attempt, the device embolized to the distal pulmonary bed and, after being rescued with a Bitome, it was appropriately repositioned with no complications and with total occlusion of the vessel.

Schistosomal glomerular disease (a review)

In this review paper schistosomal glomerulopathy is defined as an immune-complex disease. The disease appears in 12-15 per cent of the individuals with hepatosplenic schistosomiasis. Portal hypertension with collateral circulation helps the by pass of the hepatic clearance process and the parasite antigens can bind to antibodies in the circulation and be trapped in the renal glomerulus. Chronic membranousproliferative glomerulonephritis is the most commom lesion present and the nephrotic syndrome is the usual form of clinical presentation. The disease can be experimentally produced, and schistosomal antigens and antibodies, as well as complement, can be demonstrated in the glomerular lesions. Specific treatment of schistosomiasis does not seem to alter the clinical course of schistosomal nephropathy.

Patogenesis of pipe-stem fibrosis of the liver (experimental observation on murine Schistosomiasis)

Mice infected with 30 cercariae of Schistosoma mansoni developed portal and septal fibrosis due to the massive and concentrated deposition of eggs in the periportal areas which occurred following the 16th week after infection. The lesion resembled pipe-stem fibrosis seen in human hepatosplenic schistosomiasis in the following characters: portal fibrosis interconnecting portal spaces as well as portal spaces and central canals; portal inflammation; periovular granulomas; vascular obstruction and telangiectasia. The liver parenchyma maintained its normal architecture. Vascular injection techniques with Indian ink and vinylite revealed that the portal system developed numerous dilated collateral venules coming from the large and medium-sized portal branches, about 10 weeks after schistosome infection. The lodging of schistosome eggs into these collaterals resulted in granulomatous inflammation and fibrosis along all the portal tracts, thus forming the pipe-stem lesion. Although not readily demonstrable grossly, the pipe-stem fibrosis of murine schistosomiasis has many similarities with the human lesion and can be considered to have the same basic pathogenesis.

Duplex Hemodinamic evaluation of hepatosplenic mansoni schistosomiasis

Conventional ultrasonography highly contributes to a non invasive diagnosis of HS schistosomiasis (Cerri et al., 1984). The introduction of Dopple allowed new advances in the knowledge of the portal dinamics of this disease (Taylor et al., 1985; Moriyasu et al., 1986). The aim of this paper was to analize the hemodinamic behavior of the portal vessels, considering caliper, maximum flow speed, direction of flow and preferential disposition of the collateral vessels. Thirty two patients with schistosomiasis mansoni with confirmed hepatosplenic form (HSSM), were analyzed. Fourteen patients with the intestinal form, have been analyzed as a control group. The results demonstrated that the maximum speed of the portal vein in the two groups has not been significantly diferent. Nevertheless, the diameter of the PV in the hepatosplenic group has been larger. The splenic vein presented speed and caliper larger than the superior mesenteric vein. The hepatic artery has been detectly in only 40% of the cases. The hepatic veins presented normal caliper and spectral pattern. The duplex proved to be an useful technich complementar and non-invasive, in the study of the HSSM.

Esquistossomose mansoni: tratamento medicamentoso

It is the specific treatment of mansoni schistosomiasis that aims to act directed on the parasite, through chemotherapy. Constitutes fundamental indication to the treatment of schistosomiasis active forms, that is, these determined by the presence of living eggs in the feces or in material from rectal biopsy, since eventual contra indications are respected. Two are the medicaments actually used: oxamniquine, used in the single dosage of 15mg/kg, V.O. for adults and 20mg/kg V.O. for children divided in two doses, offers a percentage of 30 to 40% of cures, evaluated by quantitative "oogram" and prazinquantel, in the single dose of 60 mg/kg V.O., presents a cure index of 30% however in seriate doses, of 60mg/kg during 3 days or 30mg/kg, 6 days, cure percentage is elevated to 95% evaluated by oogram. The evaluation of the treatment by quantitative or qualitative examination methods does not show the same sensibility. The percentage of cure according to feces examination, the quantitative of Kato-Katz or the qualitative (sedimentation), showed indexes from 90 to 100% for either one of the drugs, even in single dose, which evidences the difference of methodology of therapeutic evaluation. Tolorance to both medicaments is from good to regular, with collateral effects in 30 to 40% of the patients.

An Experimental Approach to the Pathogenesis of "Pipestem" Fibrosis (Symmers' Fibrosis of the Liver)

Pathogenesis of schistosomal hepatic fibrosis ("pipestem" fibrosis of the liver) was investigated by means of the murine model. Although worm load appears as the main pathogenetic factor, alone it is not sufficient to produce that characteristic lesion. By comparing the findings in animals with heavy and prolonged Schistosoma mansoni infection, which developed or not" pipestem" fibrosis, it was observed that the lesion was more frequent in intact animals than in the splenectomized one. However, the size of the spleen, the number of recovered worms, the number of eggs per gram of liver tissue, the level of serum idiotype and anti-idiotype antibodies, the size and volume of periovular granulomas formed in the liver, all that failed to show statistically significant differences between the two groups. After analysing all these data, other factors, that apparently have been hitherto negleted, rested to explain the findings. Among them, the timing and sequence of the egg-induced intrahepatic vascular changes seemed crucial. The sequential development of intrahepatic portal vein obstruction, followed by the opening of periportal collateral veins and the continous arrival of schistosome eggs going to be lodged into the latter, appeared as essential steps in the pathogenesis of "pipestem" fibrosis

Immunopathology in ocular toxoplasmosis: facts and clues

Although parasite-mediated host cell lysis is deemed to be an important cause of tissue destruction in ocular toxoplasmosis (OT), the severity of the disease is probably correlated with hypersensitivity and inflammation. Notwithstanding, the mechanisms that regulate the inflammatory process in recurrent OT are poorly understood. Recent evidence has identified interleukin (IL) 17 as a marker for disease severity. The ocular and cerebral presence of this cytokine is generally associated with the induction of autoimmune responses in the brain and the eye. Indeed, there are indications that autoimmunity may contribute to clinical variability in the activity of OT. IL-23, which induces the proliferation of IL-17-producing cells and IL-27, which is a counterplayer to IL-17, may regulate T(H)-1-cell-mediated responses in OT. The importance of these cytokines in experimental models of uveitis and encephalitis has been recently reported. CD25(+) regulatory T-cells may control the local inflammatory response and protect the host against collateral inflammatory tissue damage. The responses of these cells to OT may be suitably tailored to cope with either an acquired or a congenital aetiology. Knowledge relating to immunoreactivity in OT has grown impressively during the past few years. Its characteristic and variable features have been identified and the potential relevance of autoimmunity has been assessed. In light of this knowledge, potential future treatment options have been considered.

Serum hyaluronan and collagen IV as non-invasive markers of liver fibrosis in patients from an endemic area for schistosomiasis mansoni: a field-based study in Brazil

Non-invasive markers of fibrosis have been used to diagnose liver fibrosis in a variety of diseases. Hyaluronic acid (HA) and collagen IV (C-IV) levels were measured in the sera of patients from an endemic area for schistosomiasis in Brazil to diagnose and to rank the intensity of liver fibrosis. Seventy-nine adult patients with schistosomiasis, in the age range of 21-82 years (49 ± 13.4) were submitted to clinical and ultrasonographic examinations. Ultrasound was employed to diagnose and categorise liver fibrosis according to World Health Organization patterns. Serum HA and C-IV levels were measured using commercial ELISA kits. Ultrasound revealed six patients with intense liver fibrosis, 21 with moderate, 23 with light and 29 without. Serum HA was able to separate individuals with fibrosis from those without (p < 0.001) and light from intense fibrosis (p = 0.029), but C-IV was not (p = 0.692). The HA diagnostic accuracy for fibrosis was 0.89. The 115.4 ng/mL cut-off level diagnosed patients with fibrosis (sensitivity 0.98, specificity 0.64). HA correlated positively with portal hypertension. Periportal fibrosis (subjective evaluation), age and collateral circulation predicted HA increase. In conclusion, we propose that serum HA can be used to identify patients with liver fibrosis in an endemic area for schistosomiasis mansoni in Brazil.

Early detection of leprosy by examination of household contacts, determination of serum anti-PGL-1 antibodies and consanguinity

A cross-sectional clinical trial in which the serum anti-phenolic glycolipid (anti-PGL-1) antibodies were analysed in household contacts (HHC) of patients with leprosy as an adjunct early leprosy diagnostic marker was conducted. The families of 83 patients underwent clinical examination and serum anti-PGL1 measurement using enzyme-linked immunosorbent assay. Of 320 HHC, 98 were contacts of lepromatous leprosy (LL), 80 were contacts of borderline lepromatous (BL), 28 were contacts of borderline (BB) leprosy, 54 were contacts of borderline tuberculoid (BT), 40 were contacts of tuberculoid (TT) and 20 were contacts of indeterminate (I) leprosy. Consanguinity with the patients was determined for 232 (72.5%) HHC. Of those 232 contacts, 183 had linear consanguinity. Forty-nine HHC had collateral consanguinity. Fifty-eight contacts (18.1%) tested positive for anti-PGL1 antibodies. The number of seropositive contacts based on the clinical forms of the index case was 17 (29.3%) for LL, 15 (25.9%) for BL, one (1.7%) for BB, 14 (24.1%) for BT, three (5.2%) for TT and eight (13.7%) for I. At the one year follow-up, two (3.4%) of these seropositive contacts had developed BT leprosy. The results of the present study indicate that the serum anti-PGL-1 IgM antibody may be useful for evaluating antigen exposure and as a tool for an early leprosy diagnosis in HHC.

Oceanografia e Química: unindo conhecimentos em prol dos oceanos e da sociedade

The marine environment is certainly one of the most complex systems to study, not only because of the challenges posed by the nature of the waters, but especially due to the interactions of physical, chemical and biological processes that control the cycles of the elements. Together with analytical chemists, oceanographers have been making a great effort in the advancement of knowledge of the distribution patterns of trace elements and processes that determine their biogeochemical cycles and influences on the climate of the planet. The international academic community is now in prime position to perform the first study on a global scale for observation of trace elements and their isotopes in the marine environment (GEOTRACES) and to evaluate the effects of major global changes associated with the influences of megacities distributed around the globe. This action can only be performed due to the development of highly sensitive detection methods and the use of clean sampling and handling techniques, together with a joint international program working toward the clear objective of expanding the frontiers of the biogeochemistry of the oceans and related topics, including climate change issues and ocean acidification associated with alterations in the carbon cycle. It is expected that the oceanographic data produced this coming decade will allow a better understanding of biogeochemical cycles, and especially the assessment of changes in trace elements and contaminants in the oceans due to anthropogenic influences, as well as its effects on ecosystems and climate. Computational models are to be constructed to simulate the conditions and processes of the modern oceans and to allow predictions. The environmental changes arising from human activity since the 18th century (also called the Anthropocene) have made the Earth System even more complex. Anthropogenic activities have altered both terrestrial and marine ecosystems, and the legacy of these impacts in the oceans include: a) pollution of the marine environment by solid waste, including plastics; b) pollution by chemical and medical (including those for veterinary use) substances such as hormones, antibiotics, legal and illegal drugs, leading to possible endocrine disruption of marine organisms; and c) ocean acidification, the collateral effect of anthropogenic emissions of CO2 into the atmosphere, irreversible in the human life time scale. Unfortunately, the anthropogenic alteration of the hydrosphere due to inputs of plastics, metal, hydrocarbons, contaminants of emerging concern and even with formerly "exotic" trace elements, such us rare earth elements is likely to accelerate in the near future. These emerging contaminants would likely soon present difficulties for studies in pristine environments. All this knowledge brings with it a great responsibility: helping to envisage viable adaptation and mitigation solutions to the problems identified. The greatest challenge faced by Brazil is currently to create a framework project to develop education, science and technology applied to oceanography and related areas. This framework would strengthen the present working groups and enhance capacity building, allowing a broader Brazilian participation in joint international actions and scientific programs. Recently, the establishment of the National Institutes of Science and Technology (INCTs) for marine science, and the creation of the National Institute of Oceanographic and Hydrological Research represent an exemplary start. However, the participation of the Brazilian academic community in the latest assaults on the frontier of chemical oceanography is extremely limited, largely due to: i. absence of physical infrastructure for the preparation and processing of field samples at ultra-trace level; ii. limited access to oceanographic cruises, due to the small number of Brazilian vessels and/or absence of "clean" laboratories on board; iii. restricted international cooperation; iv. limited analytical capacity of Brazilian institutions for the analysis of trace elements in seawater; v. high cost of ultrapure reagents associated with processing a large number of samples, and vi. lack of qualified technical staff. Advances in knowledge, analytic capabilities and the increasing availability of analytical resources available today offer favorable conditions for chemical oceanography to grow. The Brazilian academic community is maturing and willing to play a role in strengthening the marine science research programs by connecting them with educational and technological initiatives in order to preserve the oceans and to promote the development of society.

Abordagem fisioterapêutica na dor pós-operatória: a eletroestimulação nervosa transcutânea (ENT)

This study provides an update on the use of Transcutaneous Eletric Nerve Stimulation (TENS) as a non-pharmacological resource of postoperative pain relief. National and international references regarding the use of TENS for the relief of postoperative pain had been selected, highlighting its mechanism of action, parameters of application, contraindications, side-effect and results. TENS is a non-pharmacological resource that has its mechanism of action based on the gate theory. It consists of a device that emits electric impulses in the skin through electrodes. It is a low cost technique, easily applicable, presents few collateral effects, good effectiveness related to the reduction of the painful perception, allowing early mobilization and reduced pharmacological analgesic consumption. TENS represents another option in the control of postoperative pain and should be inserted in a multiprofessional context.

A systematic study of the brain base arteries in the turkey (Meleagris gallopavo)

Thirty heads with neck segments of turkeys (Meleagris gallopavo) were dissected for a systematic study of the arteries. The frequency of the arteries found was: Cerebral carotid artery, intercarotid anastomosis and internal ophthalmic artery (100%). Caudal branch of the cerebral carotid artery to the right (R) vestigial artery (70%) and developed (30%) and to the left (L) developed (70%) and vestigial artery (30%). Ventral tectal mesencephalic artery in (70%) to R and (30%) to L was the direct branch of the cerebral carotid artery to L (70%) and to R (30%) collateral branch of the developed caudal branch. Basilar artery to L in (70%) and to R (30%) formed from the developed caudal branch; rostral ventral cerebellar artery present (86.7%) and absent (13.3%) to R and L. Caudal ventral cerebellar artery to R single (73.3%), double (23.3%) and triple (3.3%); caudal ventral cerebellar artery to L single (73.3%) and double (26.7%). Dorsal spinal artery branch of caudal ventral cerebellar artery to R (80%) and to L (73.3%). The rostral branch of cerebral carotid artery showed as collateral branches the single caudal cerebral artery to R (100%) and to L (96.7%) while in (3.3%) it was double. The middle cerebral artery was single to R and L (100%). Cerebroethmoidal artery to R and L (100%) with its collateral branch to single rostral cerebral artery (90%) to R and (86.7%) to L and double (10%) to R and (13.3%) to L. Ethmoidal artery to R and to L (100%) single. The cerebral arterial circle was rostrally and caudally opened, so that the cerebral blood supply was exclusively made by the carotid system.