The analgesic activity of crotamine, a neurotoxin from Crotalus durissus terrificus (South American rattlesnake) venom: A biochemical and pharmacological study

Crotamine, a 4.88 kDa neurotoxic protein, has been purified to apparent homogeneity from Crotalus durissus terrificus venom by gel filtration on Sephadex G-75. When injected (i.p. or s.c.) in adult male Swiss mice (20–25 g), it induced a time-dose dependent analgesic effect which was inhibited by naloxone, thus suggesting an opioid action mechanism. When compared with morphine (4 mg/kg), crotamine, even in extremely low doses (133.4 μg/kg, i.p., about 0.4% of a ₅₀) is approximately 30-fold more potent than morphine (w/w) as an analgesic. On a molar basis it is more than 500-fold more potent than morphine. It is also much more potent than the lower molecular weight crude fractions of the same venom. The antinociceptive effects of crotamine and morphine were assayed by the hot plate test and by the acetic acid-induced writhing method. Therefore, both central and peripheral mechanisms should be involved. Histopathological analysis of the brain, liver, skeletal muscles, stomach, lungs, spleen, heart, kidneys and small intestine of the crotamine injected mice did not show any visible lesion in any of these organs by light microscopy. Since crotamine accounted for 22% (w/w) of the desiccated venom, it was identified as its major antinociceptive low molecular weight peptide component.     

HIV-1 Tat protein mimicry of chemokines

The HIV-1 Tat protein is a potent chemoattractant for monocytes. We observed that Tat shows conserved amino acids corresponding to critical sequences of the chemokines, a family of molecules known for their potent ability to attract monocytes. Synthetic Tat and a peptide (CysL_24–51) encompassing the “chemokine-like” region of Tat induced a rapid and transient Ca²⁺ influx in monocytes and macrophages, analogous to β-chemokines. Both monocyte migration and Ca²⁺ mobilization were pertussis toxin sensitive and cholera toxin insensitive. Cross-desensitization studies indicated that Tat shares receptors with MCP-1, MCP-3, and eotaxin. Tat was able to displace binding of β-chemokines from the β-chemokine receptors CCR2 and CCR3, but not CCR1, CCR4, and CCR5. Direct receptor binding experiments with the CysL_24–51 peptide confirmed binding to cells transfected with CCR2 and CCR3. HIV-1 Tat appears to mimic β-chemokine features, which may serve to locally recruit chemokine receptor-expressing monocytes/macrophages toward HIV producing cells and facilitate activation and infection.     

Synthesis,characterization, and evaluation of antimicrobial and cytotoxic effect of silver and titanium nanoparticles

Microbial resistance represents a challenge for the scientific community to develop new bioactive compounds. Nosocomial infections represent an enormous emerging problem, especially in patients with ambulatory treatment, which requires that they wear medical devices for an extended period of time. In this work, an evaluation of the antimicrobial activity of both silver and titanium nanoparticles was carried out against a panel of selected pathogenic and opportunistic microorganisms, some of them commonly associated with device-associated infections. Cytotoxicity assays monitoring DNA damage and cell viability were evaluated using human-derived monocyte cell lines. We show that silver-coated nanoparticles having a size of 20–25 nm were the most effective among all the nanoparticles assayed against the tested microorganisms. In addition, these nanoparticles showed no significant cytotoxicity, suggesting their use as antimicrobial additives in the process of fabrication of ambulatory and nonambulatory medical devices.From the Clinical EditorIn this study, antimicrobial activity of silver and titanium nanoparticles was evaluated against a panel of selected pathogenic and opportunistic microorganisms. Silver-coated nanoparticles of 20–25 nm size were the most effective among all the nanoparticles without significant cytotoxicity, suggesting their use as antimicrobial additives in the process of fabrication of ambulatory and nonambulatory medical devices.     

Transforming growth factor-alfa gene (TGFA), human tooth agenesis, and evidence of segmental uniparental isodisomy

We have previously reported an association between variants in the transforming growth factor-alfa gene ( TGFA ) and human tooth agenesis. To demonstrate in greater detail that TGFA contributes to tooth agenesis, we investigated additional markers in the gene. Cheek swab samples were obtained for DNA analysis from 116 patient/parent trios. Probands had at least one developmentally missing tooth, excluding third molars. Genotyping was performed using TaqMan assays. Linkage disequilibrium analysis and test of the transmission distortion of the marker alleles were performed. We confirmed that TGFA variants and haplotypes are associated with tooth agenesis. Moreover, it appears that preferential premolar agenesis is associated with TGFA , and patients with a family history of tooth agenesis would have an associated haplotype. Finally, we excluded that a TGFA microdeletion could cause sporadic agenesis in a case of upper lateral incisors and lower second premolars and suggest this case may be consequence of a segmental uniparental isodisomy.     

Use of multidimensional data analysis for prediction of lung malignity

Diagnosis of lung malignity can be predicted or confirmed not only according to the values of appropriate laboratory tests but also using multidimensional statistical analysis, which uses simultaneously all performed tests in the form of their optimal combination. The developed new way of diagnosis prediction is applied here to the results of laboratory analysis of lung tumor markers in serum as well as pleural effusion (exudate). Four laboratory tests were used and investigated in detail: carcinoembryonic antigen, CEA, in serum as well as in pleural exudate, and cytokeratin 19 fragment, CYFRA, in serum and exudate, as well. Each test represents one dimension in the investigated biomedical problem from the statistical point of view. Joint utilization of the performed laboratory tests is based on their optimized combination into a new statistical variable using a selected chemometric principle (principal component, discriminant function, or logit in logistic regression). This approach results in enhancement of diagnostic effectiveness applied for the specified purpose.     

Effects of 2,4-Dichlorophenoxyacetic acid on Rhizobium sp. membrane fluidity

The effects of 1 mM 2,4-Dichlorophenoxyacetic acid on Rhizobium sp. in pure culture was studied. In a previous work it was demonstrated that this herbicide produces an alteration on the saturated to unsaturated phospholipid acyl chains ratio. In the present paper, it was found that this alteration produces a modification on the membrane fluidity in bacteria that had achieved the stationary phase. The same results were obtained when determinations were done in liposomes from sonicated lipids of treated bacteria, indicating that changes in phospholipid acyl chains may be the main cause of membrane fluidity alteration. In addition, it was determined that leucine transport as well as Ca⁺⁺-ATPase activity (a membrane enzyme) was affected under the experimental conditions.