Medicinal electrochemistry: integration of electrochemistry, medicinal chemistry and computational chemistry.

Over the last centuries, there were many important discoveries in medicine that were crucial for gaining a better understanding of several physiological processes. Molecular modelling techniques are powerful tools that have been successfully used to analyse and interface medicinal chemistry studies with electrochemical experimental results. This special combination can help to comprehend medicinal chemistry problems, such as predicting biological activity and understanding drug action mechanisms. Electrochemistry has provided better comprehension of biological reactions and, as a result of many technological improvements, the combination of electrochemical techniques and biosensors has become an appealing choice for pharmaceutical and biomedical analyses. Therefore, this review will briefly outline the present scope and future advances related to the integration of electrochemical and medicinal chemistry approaches based on various applications from recent studies.

Lack of association of the G22A polymorphism of the ADA gene in patients with ankylosing spondylitis.

Genes located outside the HLA region (6p21) have been considered as candidates for susceptibility to ankylosing spondylitis. We tested the hypothesis that the G22A polymorphism of the adenosine deaminase gene (ADA; 20q13.11) is associated with ankylosing spondylitis in 166 Brazilian subjects genotyped for the HLA*27 gene (47 patients and 119 controls matched for gender, age and geographic origin). The HLA-B*27 gene and the G22A ADA polymorphism were identified by PCR with sequence-specific oligonucleotide probes and PCR-RFLP, respectively. There were no significant differences in frequencies of ADA genotypes [odds ratio (OR) = 1.200, 95% confidence interval (CI) = 0.3102-4.643, P > 0.8] and ADA*01 and ADA*02 alleles (OR = 1.192, 95%CI = 0.3155-4.505, P > 0.8) in patients versus controls. We conclude that the G22A polymorphism is not associated with ankylosing spondylitis.

Multiple endocrine neoplasia type 1 in Brazil: MEN1 founding mutation, clinical features, and bone mineral density profile.

OBJECTIVE: Only few large families with multiple endocrine neoplasia type 1 (MEN1) have been documented. Here, we aimed to investigate the clinical features of a seven-generation Brazilian pedigree, which included 715 at-risk family members. DESIGN: Genealogical and geographic analysis was used to identify the MEN1 pedigree. Clinical and genetic approach was applied to characterize the phenotypic and genotypic features of the family members. RESULTS: Our genetic data indicated that a founding mutation in the MEN1 gene has occurred in this extended Brazilian family. Fifty family members were diagnosed with MEN1. Very high frequencies of functioning and non-functioning MEN1-related tumors were documented and the prevalence of prolactinoma (29.6%) was similar to that previously described in prolactinoma-variant Burin (32%). In addition, bone mineral density analysis revealed severe osteoporosis (T, -2.87+/-0.32) of compact bone (distal radius) in hyperparathyroidism (HPT)/MEN1 patients, while marked bone mineral loss in the lumbar spine (T, -1.95+/-0.39), with most cancellous bone, and femoral neck (mixed composition; T, -1.48+/-0.27) were also present. CONCLUSIONS: In this study, we described clinically and genetically the fifth largest MEN1 family in the literature. Our data confirm previous findings suggesting that prevalence of MEN1-related tumors in large families may differ from reports combining cumulative data of small families. Furthermore, we were able to evaluate the bone status in HPT/MEN1 cases, a subject that has been incompletely approached in the literature. We discussed the bone loss pattern found in our MEN1 patients comparing with that of patients with sporadic primary HPT.

Determination of dopamine in synthetic cerebrospinal fluid by SWV with a graphite-polyurethane composite electrode.

This work describes an electroanalytical investigation of dopamine using cyclic voltammetry (CV) and the graphite-polyurethane composite electrode (GPU). In CV studies, well-defined redox peaks characterize the oxidation process at the GPU electrode, which is indicative of electrocatalytic effects associated with active sites on the GPU electrode surface. A new analytical methodology was developed using the GPU electrode and square wave voltammetry (SWV) in BR buffer solution (0.1 mol L(-1); pH 7.4). Analytical curves were constructed under optimized conditions (f=60s(-1), DeltaE(a)=50 mV, DeltaE(I)=2 mV) and detection and quantification limits of 6.4x10(-8) mol L(-1) (12.1 microg L(-1)) and 5.2x10(-6) mol L(-1) (0.9 mg L(-1)), respectively, were achieved. The precision of the method was checked by performing ten successive measurements for a 9.9x10(-6) mol L(-1) dopamine solution. For intra-assay and inter-assay precisions, the relative standard deviations were 1.9 and 2.3%, respectively. In order to evaluate the developed methodology, the determination of dopamine was performed with good sensitivity and selectivity, without the interference of ascorbic acid in synthetic cerebrospinal fluid, which indicates that the new methodology enables reliable analysis of dopamine.

An investigation of 131 consecutively placed wide screw-vent implants.

Between February 1995 and May 1996, 71 patients received treatment that involved 1 or more wide Screw-Vent implants. A total of 131 wide implants were placed. All patients were recalled 1 year after loading. Seven patients (14 implants) were lost to follow-up. Six implants were removed before completion of prosthetic treatment. One hundred eleven implants were evaluated at the recall examination. Almost all implants (109) supported a fixed prosthesis; in the majority of patients (93 implants), it was a fixed partial prosthesis. The mean loading time was 17 months (range, 11 to 21 months). No implants were lost during the loading period. The overall survival rate was 95%. The survival rate for mandibular implants was 94%; for maxillary implants, it was 96%. These percentages were not statistically different. Crestal bone remodeling was examined using periapical radiographs. After 17 months in function, only 3 implants (2.5%) presented bone loss beyond the first thread.

[Polyarteritis nodosa: report of a case with angiographic study]. / Poliarterite nodosa: registro de um caso com estudo angiográfico.

A case of polyarteritis nodosa (PAN) in a 54 year-old man is presented. The clinical picture showed a 6-month history of mixed sensorimotor distal symmetrical polyneuropathy in all limbs together with anorexia, weight loss, fatigue, arthralgia, myalgia, mild fever and hypertension. The laboratory studies showed leucocytosis, elevated ESR, positive HBsAg and presence of cryoglobulins. Selective renal, celiac and mesenteric angiography was performed by femoral approach and has showed innumerable aneurysms most of them in hepatic and renal circulation. After about two weeks death has occurred. A brief discussion is done on clinical aspects of PAN pointing out the importance of HBsAg determination on etiopathogenesis and angiographic study on diagnosis.