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Biomedical subjects

A Afonso

Publications and source records attributed to A Afonso.

At least 19 recordsLinked to original sources
PubMed2006

Histological and scanning electron microscopy analyses of bone/implant interface using the novel Bonelike synthetic bone graft.

Synthetic bone grafts provide an alternative to autografts and allografts. Bonelike is a patented synthetic bone graft that mimics the mineral composition of bone. The aim of the present work was to assess the biological behavior of Bonelike graft in humans, before using the material in orthopedic applications of bone regeneration, for example, in opening wedge high tibial osteotomies for medial knee osteoarthritis. Bonelike granules were implanted in cortical bone of 11 patients undergoing osteotomies, and new bone formation, osteoconductive properties, and resorption characteristics of the granules were analyzed. The granules ranged from 500 to 1000 microm and were implanted in the lateral aspect of the tibia. The patients' mean age was 59 years (range 48 to 70 years); there were eight women and three men, all suffering from medial compartment osteoarthritis of the knee. At surgery, a 1 x 1 x 1-cm cortical defect was created 3 cm distal to the entry point of the screws, in line with the long axis of tibia. The implanted Bonelike graft sample was extracted for analysis during removal of the metallic prosthesis after implantation times of 6, 9, and 12 months. Radiological follow-up, scanning electron microscopy, histological analysis, and histomorphometric measurements were conducted on the retrieved samples to assess bone regeneration in the defect area. Osteoconductive capacity was demonstrated by extensive mature bone formation around the implanted granules and high levels of percentage bone-to-graft contact (from 67-84%). Bonelike acted as an excellent bioactive scaffold, allowing the migration, proliferation, and differentiation of bone cells on its surface, and therefore regeneration of the defects was achieved in a rapid, controlled manner. Our results suggest that Bonelike graft is an excellent candidate for orthopedic applications where rapid new bone formation is a fundamental requirement.

Aged↗
PubMed2006

[Leishmania infantum/HIV co-infection: cutaneous lesions following treatment of visceral leishmaniasis].

BACKGROUND: The Mediterranean basin is an endemic region of leishmaniasis caused by Leishmania infantum. With the advent of human immunodeficiency virus (HIV) infection, the number of cases of visceral leishmaniasis has dramatically increased in this area over the last years, mainly in adults. Moreover, the presence of cutaneous lesions infested with Leishmania has been frequently reported in these patients. CASE-REPORT: A 35-year-old Portuguese woman, a former intravenous drug user HIV1-positive since 1997, developed visceral leishmaniasis in 2000, with several relapses in 2001 and 2002, treated successively with pentavalent antimonial salts (Glucantime), liposomal amphotericin B and Glucantime associated with itraconazole. Several weeks after therapy for the second relapse of visceral leishmaniasis, physical examination revealed asymptomatic erythematous papules on the face that later spread to the trunk and upper limbs. Histopathologic studies of a skin biopsy revealed a granulomatous infiltrate in the dermis with the presence of Leishmania amastigotes. After culture, the parasite was identified as L. infantum MON-1. In spite of improvement of the patient's visceral leishmaniasis with the above-mentioned treatment, the cutaneous lesions became increasingly numerous and infiltrated. After 2 months of therapy with intravenous pentamidine (4 mg/kg/3 times a week) and oral dapsone (100 mg b.i.d), the cutaneous lesions disappeared completely. Prevention with dapsone was successfully maintained for 6 months. Several weeks after discontinuation of treatment, further lesions appeared. The patient improved again on reintroduction of dapsone. DISCUSSION: This case confirmed the existence of a clinical form similar to post-kala-azar dermal leishmaniasis in a patient co-infected with L. infantum MON-1/HIV. The cutaneous lesions were resistant to classical antileishmanial drugs but disappeared on treatment with dapsone.

Adult↗
PubMed2006

Malaria parasites can develop stable resistance to artemisinin but lack mutations in candidate genes atp6 (encoding the sarcoplasmic and endoplasmic reticulum Ca2+ ATPase), tctp, mdr1, and cg10.

Resistance of Plasmodium falciparum to drugs such as chloroquine and sulfadoxine-pyrimethamine is a major problem in malaria control. Artemisinin (ART) derivatives, particularly in combination with other drugs, are thus increasingly used to treat malaria, reducing the probability that parasites resistant to the components will emerge. Although stable resistance to artemisinin has yet to be reported from laboratory or field studies, its emergence would be disastrous because of the lack of alternative treatments. Here, we report for the first time, to our knowledge, genetically stable and transmissible ART and artesunate (ATN)-resistant malaria parasites. Each of two lines of the rodent malaria parasite Plosmodium chabaudi chabaudi, grown in the presence of increasing concentrations of ART or ATN, showed 15-fold and 6-fold increased resistance to ART and ATN, respectively. Resistance remained stable after cloning, freeze-thawing, after passage in the absence of drug, and transmission through mosquitoes. The nucleotide sequences of the possible genetic modulators of ART resistance (mdr1, cg10, tctp, and atp6) of sensitive and resistant parasites were compared. No mutations in these genes were identified. In addition we investigated whether changes in the copy number of these genes could account for resistance but found that resistant parasites retained the same number of copies as their sensitive progenitors. We believe that this is the first report of a malaria parasite with genetically stable and transmissible resistance to artemisinin or its derivatives.

Amino Acid Sequence↗
PubMed2006

In vivo performance of biodegradable calcium phosphate glass ceramics using the rabbit model: histological and SEM observation.

Two MK5 (45CaO-45P(2)O(5)-5MgO-5K(2)O, in mol%) and MT13 (45CaO-37P(2)O(5)-5MgO-13TiO(2), in mol%) glasses are prepared in the meta- and pyrophosphate regions and crystallized to obtain MK5B and MT13B, respectively. MK5B was obtained by controlled crystallization, and MT13B by powder sintering. As a result of these heat treatment processes, the crystalline phases precipitated in the glassy matrix are KCa(PO(3))(3), beta-Ca(PO(3))(2), beta-Ca(2)P(2)O(7) and Ca(4)P(6)O(19) phases for MK5B and CaTi(4)(PO(4))(6), TiP(2)O(7), alpha- and beta-Ca(2)P(2)O(7) phases for MT13B. To assess the in vivo biological behavior of these glass ceramics, a mixed granulometry in the range 250-355 mum and 355-425 mum with a ratio of 1/1 was implanted for 2, 4, and 12 weeks in the tibiae of Japanese white rabbits. The results showed that the in vivo behavior was strongly affected by their solubility. All implanted materials, MK5B and MT13B, and beta-tricalcium phosphate (beta-TCP) as control material, showed signs of degradation in vivo. However, the levels of degradation were quite different throughout the implantation periods. The highest degradation was observed for MK5B glass ceramic and the lowest for MT13B with beta-TCP in-between. All implanted materials allow for new bone formation in the bone defect area. At the longest implantation period (12 weeks), the MT13B and beta-TCP materials were almost completely surrounded by new bone tissue, whereas MK5B showed some unfilled spaces. This behavior is discussed in terms of the high degradation observed in previous studies.

Absorbable Implants↗
PubMed2005

Side effects in sea bass (Dicentrarchus labrax L.) due to intraperitoneal vaccination against vibriosis and pasteurellosis.

Sea bass (Dicentrarchus labrax L.) were injected intraperitoneally with monovalent (Photobacterium damselae subsp. piscicida or Vibrio anguillarum) and divalent (Ph. damselae subsp. piscicida and V. anguillarum) vaccine formulations, with or without adjuvants (mineral oil, liposome or alginate), to evaluate the short and long-term pathological effects. Eight animals from each group were sampled one, two, four and 11 months after intraperitoneal injection. The acute peritoneal response and the progression to a chronic status were evaluated by analysing peritoneal leucocytes collected during the first days post-injection. To evaluate the chronic response, the late peritoneal leucocyte response was analysed and the peritoneal cavity was examined and the intra-abdominal lesion level scored based on a pre-defined scale. Correlation between leucocyte exudative response, tissue inflammatory response and the development of granuloma were sought. The acute leucocyte response was characterized by an early (24-48 h) mobilization of neutrophils and macrophages, with phagocyte numbers dependent on the formulation, but no significant variations were observed in lymphocytes/small cells and EGCs. Later on, a steady increase occurred in lymphocytes/small cells and EGCs and a high concentration in neutrophils and macrophages was maintained up to 30-60 days in groups i.p. injected with oil adjuvanted formulations with antigen. All the lesions observed were moderate, indicating that in sea bass, the pathological effects due to intraperitoneally injected vaccines are less severe than in other fish species. The divalent oil adjuvanted vaccine induced the most severe side effects, with macroscopic granulomas consistently present up to 11 months.

Adjuvants, Immunologic↗
PubMed2004

Normal-law quantile phase filters for mode conversion in single-mode fibers applied to wavelength blockers.

We propose the definition of a new family of complex-amplitude filters. These filters are optimal for mode conversion in single-mode fibers and give rise to a large variety of spatial designs. Among them, we focus on a few that are easy to manufacture and implement, in particular, in an array shape, and present some technical advantages such as tolerance to positioning. In the second part, we discuss their implementations by using various technologies and the effect of some technical constraints on filter shape and phase distribution. Finally, we illustrate their uses in the case of a dynamic wavelength blocker within the frame of wavelength-division-multiplexing network systems.

Journal Article↗
PubMed2003

Cutaneous infection due to Scedosporium apiospermum in an immunosuppressed patient.

Scedosporium apiospermum, the anamorphic form of Pseudallescheria boydii, is a filamentous fungus with low inherent virulence. Increasing numbers of cases of this infection have been reported probably related to the rising number of immunosuppressed persons. Apart from mycetoma, cutaneous and subcutaneous infection is rarely encountered in clinical practice. We describe a case of cutaneous infection caused by Scedosporium apiospermum in a subject with rheumatoid arthritis and diabetes mellitus who was submitted to long-term therapy with cyclosporin and corticosteroids. Histopathologic examination of a skin biopsy showed a granulomatous infiltrate with hyaline septate hyphae. Culture of two skin biopsies taken at two different observations of the woman, 3 weeks apart, allowed isolation of Scedosporium apiospermum. Therapy with itraconazole, 400 mg/day, for 3 months was effective in curing the infection.

Antifungal Agents↗
PubMed2003

Pyoderma gangrenosum or leukaemia cutis?

We report a case of atypical bullous pyoderma gangrenosum associated with acute myeloid leukaemia in which we found atypical myeloid cells within the skin lesion. Although there have been many reported cases of leukaemia-associated pyoderma gangrenosum, the finding of myeloblasts in the skin has rarely been described.

Antineoplastic Agents↗
PubMed2001

Psychoneuroendocrine characteristics of common obesity clinical subtypes.

OBJECTIVE: To relate psychological profiles, cerebral asymmetry and the hypothalamus-pituitary-adrenal axis (HPA) reactivity to clinical characteristics of common obesity. METHODS: Sixty consecutive adult female overweight and obese patients attending the outpatient endocrine department were included in this study. Clinical evaluation specifically selected a priori the following indexes: obesity age of onset, parenthood obesity, carbohydrate craving, binge eating with purging, obesity degree (defined by the body mass index (BMI)--weight (kg)/height (m(2))), body fat distribution (defined by the abdominal--thigh ratio (A/T)) and initial weight loss after medical treatment. Psychological evaluation was performed with the Minnesota Multiphasic Personality Inventory (MMPI). In the last 30 patients, the Edinburgh Inventory of Manual Preference (EIMP) and the corticotrophin-releasing hormone (CRH) test were also performed. RESULTS: Clinical characteristics defined a priori were independent variables as evaluated by contingency table analysis. Factorial analysis of variance (ANOVA) revealed a significantly different MMPI profile, according to parental obesity, with post-hoc significantly higher scores on the hypochondriasis (Hs), paranoia (Pa), psychasthenia (Pt) and schizophrenia (Sc) scales in patients with obese parents. Obese patients presented significantly higher dichotomized manual preference indexes in relation to overweight patients. Parental obesity, binge eating behaviour with purging, body fat distribution and the dichotomized manual preference index were independent significant factors for the ACTH response in the CRH test, together explaining 41% of the response variability. Age of onset of obesity and the dichotomized manual preference index were independent and significant factors for the cortisol response, together explaining 37% of its variability. A non-normal distribution was found for the ACTH response: high- and low-responders presented significantly different MMPI profiles, with high-responders presenting higher scores on all clinical scales except masculinity/femininity (Mf). CONCLUSION: Overweight/obese subjects with parental obesity present a distinctive personality profile and a higher ACTH response in the CRH test. Cerebral asymmetry may be a relevant factor for obesity development and is associated with the HPA reactivity. HPA reactivity is a sensitive index integrating clinical, psychological and neural asymmetric factors. International Journal of Obesity (2001) 25, 24-32

Adipose Tissue↗
PubMed2000

Glycogen granules in resting and inflammatory rainbow trout phagocytes--an ultrastructural study.

The ultrastructural image of glycogen granules in the cytoplasm of rainbow trout phagocytes in sections stained by the conventional lead or uranyl-lead stains is highly dependent on fixation conditions, the granules being visible only when adequate fixation protocols are used. Morphometry of samples processed for the detection of peroxidase or esterase activities (to specifically label neutrophils and macrophages, respectively), and simultaneously stained for the specific detection of glycogen, showed that inflammatory peritoneal neutrophils were richer in glycogen granules than resting neutrophils. This increase in glycogen content occurs after the migration from the haematopoietic tissues and peripheral blood to the inflamed foci. Glycogen granules could not be found in resting peritoneal macrophages but were found in inflammatory macrophages. The macrophage granules occurred in smaller amounts than in neutrophils, and consisted of granules identical to those of neutrophils together with significantly smaller granules. No evidence for the utilization of glycogen by neutrophils phagocytosing bacteria within the peritoneal cavity was found.

Animals↗
PubMed2000

Bacillary angiomatosis by Bartonella quintana in an HIV-infected patient.

Bacillary angiomatosis and bacillary peliosis are opportunistic infections caused by Bartonella henselae and Bartonella quintana, which occur in patients with late-stage infection. We report a case of bacillary angiomatosis in an HIV-infected patient with skin, bone, and probably liver involvement, The identification of the agent (B quintana ) was done by polymerase chain reaction in the skin specimen. The patient had complete regression of all lesions after a 6-month regimen of oral erythromycin.

AIDS-Related Opportunistic Infections↗
PubMed2000

Primary cutaneous CD30-positive large cell lymphoma.

Primary cutaneous CD30-positive large cell lymphoma is a recently described entity, recognized by immunohistochemical criteria. Spontaneous regression may occur and although relapses are frequent, most patients have a favourable prognosis. We describe a 83-year-old woman with a large ulcerated tumour on her right forearm, with 2 months evolution. Histological and immunohistochemical examination revealed a CD30-positive large cell lymphoma. Systemic involvement was not detected. The tumour regressed spontaneously. Cutaneous relapses occurred one year later, all with spontaneous regression. After a 2-year follow-up period, the patient is well, without concurrent extracutaneous disease. This case is in keeping with other reports of spontaneous regression and favourable outcome of this type of cutaneous lymphoma.

Aged↗
PubMed1999

Identification of pharmacokinetically stable 3, 10-dibromo-8-chlorobenzocycloheptapyridine farnesyl protein transferase inhibitors with potent enzyme and cellular activities.

Farnesyl protein transferase (FPT) is a promising target for the development of cancer chemotherapeutics because it is responsible for the farnesylation of oncogenic p21 Ras proteins which are found in nearly 30% of all human cancers and necessary for cellular development and growth. The recent discovery and progression to phase II clinical trials of trihalobenzocycloheptapyridine Sch-66336 as a potent inhibitor of FPT with oral, in vivo efficacy in mice have spawned extensive structure-activity relationship studies (SAR) of this class of compounds. Of the many trihalobenzocycloheptapyridine analogues prepared, we have identified several which inhibit FPT and cellular proliferation at single-digit nanomolar concentrations and which have good pharmacokinetic properties in mice.

Administration, Oral↗
PubMed1999

Analogs of 4-(3-bromo-8-methyl-10-methoxy-6,11-dihydro-5H-benzo[5,6]-cyclo hepta[1,2-b]pyridin-11-yl)-1-(4-pyridinylacetyl)piperidine N-oxide as inhibitors of farnesyl protein transferase.

A series of 3-substituted analogs 3 of 4-(3-bromo-8-methyl-10-methoxy-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2 b]pyridin-11-yl)-1-(4-pyridinylacetyl)piperidine N-oxide 2 was prepared and evaluated as FPT inhibitors. The objective of this study was to identify other substituents at C3 in this series of FPT inhibitors that would have the FPT potency enhancement similar to that found for a C3 bromo substituent. The 3-methyl analog 17b was found to be tenfold less active than 2, and other C3 substituents having more steric bulk were found to cause a further reduction in activity.

Alkyl and Aryl Transferases↗
PubMed1999

Analogues of 1-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo-[5,6]-cyclohepta [1,2-b]pyridin-11-yl)piperidine as inhibitors of farnesyl protein transferase.

The synthesis of several 4-pyridylacetyl N-oxide derivatives of 4-(3-bromo-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2-b]-pyridin-11-yl)pi perazine/piperidine 3 is described. This study was aimed at identifying fomesyl protein transferase (FPT) inhibitors in these two series of tricycles containing different phenyl ring substituents. The in vitro activity profile of the initial group of compounds 7a-7g led to the synthesis of the 8-methyl-10-methoxy and 8-methyl-10-bromo analogues 7i, 13i, and 13j. The 11R(-) enantiomers of these compounds were found to exhibit potent in vitro FPT inhibition activity.

Alkyl and Aryl Transferases↗
PubMed1999

Altered cytokine balance in the tear fluid and conjunctiva of patients with Sjögren's syndrome keratoconjunctivitis sicca.

PURPOSE: To compare epidermal growth factor (EGF) concentration in tear fluid and levels of inflammatory cytokines in the conjunctival epithelium of patients with Sjögren's syndrome keratoconjunctivitis sicca with those of normal controls. METHODS: Schirmer 1 tear testing, corneal fluorescein staining and conjunctival impression cytology for quantitation of goblet cell density were performed in ten patients with Sjögren's syndrome-associated keratoconjunctivitis sicca and ten asymptomatic normal controls. ELISA was used to detect the concentration of EGF in tear fluid and interleukin 6 in lysates of conjunctival cytology specimens obtained from all subjects. The levels of RNA transcripts encoding inflammatory cytokines [interleukin 1alpha_(IL-1alpha), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor alpha_(TNF-alpha), and transforming growth factor beta1 (TGF-beta1)] as well as a housekeeping gene (G3PDH) were evaluated in conjunctival cytology specimens taken from all subjects by semiquantitative competitive reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Decreased tear fluid EGF concentration was noted in Sjögren's syndrome patients (mean 0.68 +/- 0.59 ng/ml) compared to controls (mean 1.66 +/- 0.45 ng/ml, P = 0.004). Significantly increased levels of IL-1alpha, IL-6, IL-8, TNF-alpha and TGF-beta1 RNA transcripts were found in the conjunctival epithelium of Sjögren's syndrome patients compared to controls (P < 0.05), while the level of G3PDH was similar in both groups. The concentration of IL-6 protein was significantly higher in Sjögren's syndrome conjunctiva samples (P = 0.012). Tear EGF concentration correlated with Schirmer 1 scores (rho 0.767, P < 0.001), corneal fluorescein staining scores (rho -0.562, P = 0.01), conjunctival goblet cell density (rho 0.661, P = 0.001) and the levels of IL-1alpha_and IL-8 RNA in the conjunctival epithelium (rho -0.677 and -0.747, respectively, P = 0.001). Both IL-1alpha_and IL-8 RNA in the conjunctival epithelium increased as Schirmer 1 scores decreased (P </= 0.001). IL-8 RNA level correlated with corneal fluorescein staining (rho 0.690, P = 0.001) and conjunctival goblet cell density (rho -0.767, P < 0.001). A significant decrease in IL-8 RNA level, corresponding to improvement in irritation symptoms and ocular surface disease, was observed in six eyes after two weeks of topical corticosteroid therapy. CONCLUSIONS: The balance of cytokines in the tear fluid and conjunctival epithelium is altered in Sjögren's syndrome. The severity of keratoconjunctivitis sicca in this condition increases as tear fluid EGF concentration decreases and levels of inflammatory cytokines in the conjunctival epithelium increase. These findings provide new insight into the pathogenesis of keratoconjunctivitis and provide potential targets for therapy.

Adult↗
PubMed1999

Loss of heterozygosity on chromosome 13 is associated with advanced stage prostate cancer.

PURPOSE: In order to investigate the possible involvement of a tumor suppressor gene(s) on chromosome 13 in prostatic neoplasms, we performed loss of heterozygosity (LOH) analysis on normal and tumor pairs from 36 prostate cancer patients. MATERIALS AND METHODS: Pure DNA was obtained from carcinoma cells and normal epithelium by tissue microdissection. The DNA had previously been analyzed for LOH on chromosomes 8 and 16. After an initial pilot experiment to determine the region(s) of significant LOH from 9 loci on chromosome 13q, 3 loci at and near the Rb1 locus (D13S153, D13S1319, and D13S1303) were chosen for further study. RESULTS: The overall rate of LOH on chromosome 13 was 27.3%. Four tumors exhibited LOH at all 3 loci. Two tumors exhibited LOH at D13S153 but not at the other, more telomeric loci; two additional tumors had loss at D13S1303 or D13S1319 but not D13S153. These data suggest that a tumor suppressor gene involved in prostate cancer may be located just telomeric to Rb1. Analysis of clinical and pathological data from carcinomas with and without loss shows that chromosome 13q LOH is correlated with advanced stage prostate cancer. CONCLUSIONS: Our LOH data suggests that there may be a tumor suppressor gene telomeric to Rb1 that is potentially involved in prostate cancer progression. Identification of this gene may be valuable in providing diagnostic and prognostic information for prostate cancer patients.

Chromosome Mapping↗