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Biomedical subjects

M Rodrigues

Publications and source records attributed to M Rodrigues.

At least 19 recordsLinked to original sources

Pharmacological assay of Cordia verbenacea V: oral and topical anti-inflammatory activity, analgesic effect and fetus toxicity of a crude leaf extract.

Cordia verbenacea D.C. (Borraginaceae) is a perennial bush plant that grows widely along the southeastern coast of Brazil. Its leaves have been used in folk medicine for their anti-ulcer, anti-inflammatory and cicatrizing activities. We have already described the anti-inflammatory properties of C. verbenacea and its low toxicity in different acute animal models. In the present study, we investigated the anti-inflammatory activity in sub-chronic animal models of a crude leaf lyophilized extract when administered by oral route or topically applied, and concomitantly, its analgesic potency and toxicity to the fetus. Topical administration of the extract inhibited nystatin-induced edema proportionally to the doses used, and this effect at a dose of 4.56 mg/kg body wt. was similar to that observed with 6.0 mg/kg body wt. of naproxen. In miconazole-induced edema, the leaf extract at a dose of 1.24 mg/kg body wt., orally administered, has a very similar effect as compared to nimezulide (2.5 mg/kg body wt.) and dexamethasone (0.2 mg/kg body wt.). At an oral dose of 2.48 mg/kg body wt. the extract showed a very low analgesic effect, and total absence of fetus toxicity at doses of less than 7.44 mg/kg body wt.

Administration, Cutaneous↗

Dipyridamole increases the cytotoxicity of cisplatin in human larynx cancer cells in vitro.

This paper describes the effect of dipyridamole (DIP) on the cytotoxicity of cisplatin in HEp-2 human larynx cancer cells in vitro and the nature of the interaction between cisplatin and dipyridamole. Cytotoxic assays were performed to obtain the IC50 for cisplatin. The cells were treated with 0, 20, 40, 80, 120 or 200 microM cisplatin, with or without a single concentration of DIP and incubated for 60 min at 37 masculine C and 5% CO2 for 3 days and then counted with a hemocytometer. The accumulation of cisplatin in the cells was measured by atomic absorption and fluorescence was used to determine the membrane binding constant of DIP. In the presence of 10, 20 and 30 microM DIP, the IC50 of cisplatin was reduced by 25, 60 and 82% in HEp-2 cells. Combination index analysis revealed that cisplatin and DIP interact synergistically. In larynx cancer cells, the accumulation of cisplatin increased by 13, 27 and 65% as the DIP concentration was increased from 10 to 20 and 30 microM, respectively. The binding constant of DIP to the cell membrane was estimated to be 0.36 +/- 0.12 mg/ml(-1) (N = 2) by fluorescence and cisplatin did not suppress DIP fluorescence. These results suggest that DIP significantly enhances cisplatin cytotoxicity in HEp-2 cells by increasing cisplatin accumulation, probably by altering the cell membrane as suggested by its binding constant. The results obtained reinforce the importance of combination therapy to reduce the doses of chemotherapeutic drugs and therefore the side effects of chemotherapy.

Antineoplastic Agents↗

New approaches in nuclear medicine for early diagnosis of Alzheimer's disease.

Dementia, Alzheimer's disease (AD) being the most common cause of it, is a major and growing medical and social problem, particularly in the advanced age, with the highest rate in the population over 75 y. Recent sophisticated therapeutic measures require more sensitive diagnostic tests to recognize early stages of the disease. In this paper, the current neuronuclear imaging literature is reviewed with regard to early and differential diagnosis of dementia. Functional imaging with single photon emission computed tomography (SPECT) and positron emission tomography (PET) could provide the clinician with additional information complementary to morphological assessments, thus contributing to achieve a more adequate diagnosis, and also with information regarding prodromal stages of AD.

Alzheimer Disease↗

Sentinel lymph node detection with large human serum albumin colloid particles in breast cancer.

Detection of metastatic involvement of lymph nodes is essential for management and prognostic evaluation in breast cancer patients. The success of lymphatic mapping depends on identifying the sentinel lymph node(s) draining the primary tumour. However, when mapping is performed with a radiocolloidal agent, the number of hot lymph nodes varies with the agent and its size, among other factors. In this study, we evaluated prospectively the detection rate of sentinel lymph nodes in breast cancer when injecting large particles (100-600 nm) of human serum albumin colloids (Senti-Scint). In 128 consecutive breast cancer patients without palpable lymph nodes, pre-operative static lymphoscintigraphic mapping of the breast was performed after subcutaneous injection of 15 MBq of the radiocolloid. Lymphoscintigrahic results were compared with intra-operative surgical gamma detection probe and blue dye mapping data. Pre-operative lymphoscintigraphy and surgical gamma detection probe both correctly detected 203 sentinel lymph nodes in 122/128 patients (95%), while blue dye mapping showed only 183 sentinel lymph nodes in 82% of the patients. Only one or two sentinel lymph nodes were identified in each patient, which allowed the surgeon easily to find the sentinel lymph node(s) intra-operatively. In conclusion, lymphoscintigraphy with large particles of human serum albumin colloids is a helpful and reliable procedure for the surgical management of breast cancer.

Adult↗

Identification of antibodies to Leishmania silent information regulatory 2 (SIR2) protein homologue during canine natural infections: pathological implications.

Dogs are the domestic reservoir of zoonotic visceral Leishmaniasis caused by Leishmania infantum in the Mediterranean basin and thus constitute an important health problem in both human and veterinary medicine. Until vaccines become available, conventional measures such as epidemiological surveillance including reservoir control will be among the practical options for prevention and containment of the disease. We have recently characterised novel Leishmania sp. genes encoding parasite proteins named (LmS3a: homologous to mammalian ribosomal protein S3a; LmSIR2: homologous to the silent information regulatory 2 protein family; LimTXNPx: homologous to the peroxiredoxin family with N-terminal mitochondrial leader sequence) that may contribute to the host immune dysfunction in murine experimental Leishmaniasis. In the present study we have investigated the humoral responses against the parasite antigens in groups of L. infantum-infected dogs with different clinical status: symptomatic and asymptomatic with DTH positive or negative test. The determination of immunoglobulin (Ig) isotypes revealed high levels of total IgG in both symptomatic and asymptomatic animals when compared to IgM. Furthermore, the IgG2 appeared to be the predominant subclass of Ig present in the sera of infected animals particularly in the case of symptomatic dogs. The IgG subclass reactivity analysis revealed a broad specific recognition range of parasite recombinant antigens. Interestingly, differential profiles of IgG1 and IgG2 antibody reactivity were observed in asymptomatic and symptomatic dogs. The LmSIR2 protein was found to be a highly reactive molecule with IgG2 from most of the asymptomatic and symptomatic animals. Considering the fact that LmSIR2 secreted by the parasites can be bound and taken up by neighbouring cells, the latter could be a target for anti-LmSIR2 antibodies and this may contribute to the immunopathological alterations and host tissue damage. The implications of these observations in the pathogenesis of Leishmaniasis are discussed.

Animals↗

Metabolic impairment of brain metabolism in patients with Lewy body dementia.

A reliable assessment of dementia is essential for a differentiated treatment. Recent studies have demonstrated a poor accuracy of clinical criteria for diagnosis of Lewy body dementia. Diffuse Lewy body disease (LBD) is the second most common cause of senile degenerative dementia and is characterized histologically by the occurrence of Lewy bodies in allocortical, neocortical and subcortical structures. Seven male patients (mean age 81 years) with clinically suspected diffuse LBD were investigated with 18F-fluorodeoxyglucose (FDG)-PET using a Siemens ECAT-ART PET-scanner. The 18F-FDG-PET showed a diffuse glucose hypometabolism in the entire cerebral cortex with relative sparing of the primary sensory-motor cortex in all patients. This diffuse metabolic impairment in the entire cortex with relative sparing of central region seems to be a typical pattern for LBD, distinct from Alzheimer's disease.

Aged↗

Postnatal depression and infant growth and development in low income countries: a cohort study from Goa, India.

BACKGROUND: Postnatal depression is a recognised cause of delayed cognitive development in infants in developed countries. Being underweight is common in South Asia. AIMS: To determine whether postnatal depression contributes to poor growth and development outcomes in Goa, India. METHODS: Cohort study for growth outcomes with nested case-control study for developmental outcomes. A total of 171 babies were weighed and measured at 6-8 weeks following birth. The following measures were used: Edinburgh Postnatal Depression Scale for maternal mood, and sociodemographic and infant health variables. Outcome measures were: weight (<5th centile), length (<5th centile), and Developmental Assessment Scale for Indian Infants scores at six months. RESULTS: Postnatal depression was a strong, and independent, predictor of low weight and length and was significantly associated with adverse mental development quotient scores. CONCLUSIONS: This study provides evidence for the first time that postnatal depression, a potentially treatable disorder, is a cause of poor growth and development in South Asia.

Adult↗

Leishmania infantum MON-98: infection in a dog from Alto Douro, Portugal.

We report the isolation of Leishmania infantum zymodeme MON-98 in Portugal, its first known occurrence outside the focus of El Agamy, Egypt. One dog found to be infected with Acanthocheilonema dracunculoides during a survey of canine filariosis in the Alto Douro region, north-east Portugal, was also discovered to have Leishmania in bone marrow. The isolated strain was identified by isoenzyme analysis. A search for other possible cases of L. infantum MON-98 infection in dogs, vectors and particularly humans is necessary to establish the real epidemiological importance of this zymodeme in the endemic region of Alto Douro.

Animals↗

Decision-making capacity and surrogate designation in French ICU patients.

OBJECTIVE: To evaluate the capacity and willingness of French-speaking patients to designate a surrogate within 24 h of their ICU admission. French laws fail to indicate what should be done when an otherwise legally competent patient transiently loses his decision-making capacity. DESIGN: Surrogate designation was prospectively evaluated during two study periods. Only conscious patients were assessed using the Glasgow Come Score in the first study period, and all admitted patients were assessed in the second period. Decision-making capacity was evaluated using the Mini Mental Status Examination (MMSE) in the second study period. SETTING: Twenty six-bed intensive care unit (ICU) in a French teaching hospital. PATIENTS AND PARTICIPANTS: Over a 8-month period 495 patients were included in the study, 415 in the first study period and 80 in the second. MEASUREMENTS AND RESULTS: Of the 495 patients 185 (37.3%) were interviewed, and 62.7% designated a surrogate. The surrogate was the spouse in 50% of cases and a child in 28.4%. Only 25.8% were considered to have decision-making capacity; 78.1% of competent patients and 28% of the patients without decision-making capacity agreed to designate a surrogate. CONCLUSIONS: Surrogate designation by a patient should be evaluated in the light of the decision-making capacity of the patient. The traditional French paternalism still practiced by many French physicians appears out of tune with the wishes of their patients. We suggest that there is a need for developing a simple and effective tool for assessing decision-making capacity in ICU patients.

Aged↗

In vitro adsorption of 99Tc(m)-MIBI, 99Tc(m)-tetrofosmin, 99Tc(m)-furifosmin and 99Tc(m)O4- onto tubes.

Adsorption of radiopharmaceuticals onto disposable syringes has been reported to amount to levels of almost 50%. Data on adsorption of radiopharmaceuticals onto materials used for in vitro studies are extremely limited. We assessed the extent of adsorption of 99Tc(m) hexakis(2-methoxyisobutylisonitrile) (99Tc(m)-MIBI), 99Tc(m)-tetrofosmin, 99Tc(m)-furifosmin and 99Tc(m)O4 onto tubes used for in vitro measurement of cellular uptake of these radiopharmaceuticals. The influence on adsorption of different incubation media, temperature and time of incubation was evaluated. Total (not corrected for adsorption) uptake was compared with corrected, net cellular uptake in SK-BR-3, MCF-7 and liposarcoma cell lines. Values of adsorption ranging from 0.94+/-0.13% to 7.07+/-0.46% were found. The extent of adsorption of all the radiopharmaceuticals varied with the type of incubation medium and the incubation temperature. With 99Tc(m)-furifosmin, adsorption was dependent on the incubation time as well on the incubation temperature and some of the incubation media investigated. Our findings indicate that systematic investigations to evaluate the adsorption of radiopharmaceuticals onto materials used during in vitro studies of cellular uptake should be considered a mandatory aspect of quality control.

Adsorption↗

Verapamil decreases accumulation of 99Tcm-MIBI and 99Tcm-tetrofosmin in human breast cancer and soft tissue sarcoma cell lines.

99Tcm-methoxyisobutylisonitrile (99Tcm-MIBI) and 99Tcm-tetrofosmin are cationic tracers recognized by the efflux pump P-glycoprotein (Pgp). Verapamil has been shown to be a competitive inhibitor of Pgp, and was one of the first multidrug-resistant reversing agents identified. The aim of this preclinical in vitro study was to evaluate the effects of verapamil on the accumulation of 99Tcm-MIBI and 99Tcm-tetrofosmin in the human breast cancer cell lines MCF-7 and SK-BR-3 and in the human soft tissue sarcoma cell lines SW 982 and SW 1353, in comparison with respective control cells, i.e. without preincubation with verapamil. After preincubation with 10 or 100 microM of verapamil for 15 or 30 min, the 99Tcm-MIBI and 99Tcm-tetrofosmin accumulation in cells was assessed at 10, 30 and 60 min after incubation with these tracers. Addition of verapamil caused a decline in the accumulation of the two tracers at all incubation times, as compared with control cells. These effects of verapamil were neither dose- nor preincubation time-dependent in most cells. Our data indicate that verapamil is not a promising agent for increasing the sensitivity of scintigraphy with 99Tcm-MIBI or 99Tcm-tetrofosmin, or for evaluating Pgp tumour status in these types of tumours.

Adenocarcinoma↗

Developmental milestones of vertically HIV infected and seroreverters children: follow up of 83 children.

The aim of the study was to detect neurological abnormalities in human immunodeficiency virus (HIV) infected children. This was achieved by a prospective evaluation, from November/1995 to April/2000, of 43 HIV infected children (group I) and 40 HIV seroreverters children (group II) through neurological exam and neurodevelopmental tests: Denver Developmental Screening Test (DDST) and Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS). A control group (III), of 67 children, were evaluated by CAT/CLAMS. Hyperactivity, irritability and hypotonia were the findings on neurological examination, without statistical differences between group I and II. On CAT/CLAMS, the group I developmental quotient (DQ) was significantly lower than the other groups. The same occurred in DDST, with group I presenting significantly more failures than group II. Nineteen HIV children of group I had brain computed tomographic scan, with abnormalities in three of them (basal ganglia calcification, white matter hypodensity and asymmetry of lateral ventricles). We conclude that in HIV infected children a neurodevelopment delay occur early in the disease, and it can be detected by screening tests.

Child↗

[Rett syndrome: retrospective and prospective study of 28 patients].

From November 1982 to May 1999, 28 children with Rett syndrome were followed-up for a medium period of 6 years and 2 months. Regression of developmental milestones started at the age between 5 and 20 months. Nineteen cases of typical Rett syndrome had uneventful pre and perinatal periods, loss of previously acquired purposeful hand skills, mental and motor regression and developed hand stereotypies; sixteen had head growth deceleration and 12 gait apraxia. Nine patients were atypical cases, 2 formes frustres, 2 congenital, 3 with early seizure onset, 1 preserved speech and 1 male. Epilepsy was present in 21 patients, predominantly partial seizures and the drug of choice was carbamazepine (15 patients). In the initial evaluation most patients were distributed on Stages II and III and on follow-up on Stages III and IV. Three children died.

Adolescent↗

Effects of intravitreal corticosteroids in the treatment of Bacillus cereus endophthalmitis.

OBJECTIVE: To investigate whether intravitreal corticosteroid therapy reduces the extent of inflammatory intraocular tissue damage caused by Bacillus cereus endophthalmitis. METHODS: New Zealand white rabbits were inoculated with 1 x 10(6) B cereus organisms and randomized to receive no treatment (control eyes; n=14), intravitreal vancomycin hydrochloride (n=13), or a combination of intravitreal vancomycin and dexamethasone sodium phosphate (n=13) after 24 hours. The eyes were examined and graded for clinical signs of infection and inflammation on days 7 and 14, followed by enucleation for histopathologic analysis. RESULTS: Both treated groups had significantly less clinical sequelae than controls on day 7. By day 14, eyes given combination treatment had significantly less clinically graded corneal (P=.03) and conjunctival (P=.007) inflammation than eyes treated with vancomycin. Histopathologic analysis revealed a significant decrease in inflammatory changes between all treated eyes and controls at day 14. The only statistically significant difference between eyes given combination treatment and eyes given vancomycin alone was in the retina (P=.03). CONCLUSIONS: Intravitreal corticosteroids may enhance the recovery from B cereus endophthalmitis when given in conjunction with intravitreal antibiotics. The beneficial effect of corticosteroids is noted clinically, but not histologically, by day 14 after single-dose treatment in rabbits. CLINICAL RELEVANCE: This study provides evidence that the use of intravitreal corticosteroids with antibiotics for the treatment of B cereus endophthalmitis may lead to an improvement compared with the use of antibiotics alone. Arch Ophthalmol. 2000;118:803-806

Animals↗

Influence of drugs on myocardial iodine-123 metaiodobenzylguanidine uptake in rabbit myocardium.

About 15 years ago, iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging was introduced for the evaluation of myocardial sympathetic nerve function. Two uptake mechanisms for MIBG have so far been identified: uptake type I, a saturable, energy-dependent mechanism, and uptake type II, a non-saturable, energy-independent mechanism. We incubated isolated rabbit myocardial tissue samples with 123I-MIBG in order to assess the uptake characteristics and the influence of varying incubation conditions. Furthermore, we examined the effects of several drugs and uptake inhibitors on the myocardial uptake of MIBG. The in vitro myocardial uptake of MIBG reached a steady plateau at 23.87%+/-3.63% after 1 h, i.e. a concentration gradient of 10, in a thermo-independent manner within a concentration range from 1.5 to 1500 microM. This indicates an unsaturable uptake process in the tested concentrations. Preincubation with the following drugs caused a significant inhibitory effect on myocardial MIBG uptake: haloperidol, levomepromazine, metoprolol, labetalol and clomipramine. According to our findings, the uptake mechanism seems to be an unspecific process, but the concentration gradient of 10 makes passive diffusion unlikely. Further studies with uptake-II-blocking substances as well as with isolated myocardial cells will be needed to clarify the nature of the myocardial MIBG uptake mechanism.

3-Iodobenzylguanidine↗

Odontoid fractures: high complication rate associated with anterior screw fixation in the elderly.

This study is a retrospective analysis of patients older than 65 years with odontoid fractures. The series consisted of 29 consecutive patients with odontoid fractures (18 women, mean age 78, range 66-99 years). Twenty-six patients were neurologically intact, Frankel E, whereas three had neurological symptoms: two Frankel D and one Frankel C. Eleven patients were treated with anterior screw fixation according to Böhler, seven with a posterior C1-C2 fusion. Ten patients with either minimally displaced fractures or with complicating medical conditions were treated conservatively. At follow-up, 7/7 patients with posterior fusion had healed without any problems, whereas 8/11 patients treated with anterior screw fixation, and 7/10 conservatively treated patients were either failures or had healed, but after a complicated course of events. We conclude that anterior screw fixation according to Böhler is associated with an unacceptably high rate of problems in the elderly. Probable causes may be osteoporosis with comminution at the fracture site, or stiffness of the cervical spine preventing ideal positioning of the screws. As non-operative treatment also often fails, the method of choice seems to be posterior C1-C2 fusion.

Aged↗

[Intravenous immunoglobulin in children with Guillain-Barré syndrome].

We report our experience with intravenous immunoglobulin (IVIG), plasmapheresis and supportive care in 13 patients with the Guillain-Barré syndrome. Seven of 13 patients received IVIG, 2 plasmapheresis and 4 supportive care. At 15th day after IVIG administration, all patients in this group had improved at least one disability grade. In the plasmapheresis group, 1 improved at 5th day after the procedure. Two of the 4 patients that received supportive care improved at 20th day of evaluation. In the IVIG group, the final scores were lower and had no relapses. These results suggest faster clinical improvement with IVIG when compared with supportive measures.

Child↗