Noradrenergic and opioidergic influences on the antinociceptive effect of clomipramine in the formalin test in rats

Although tricyclic antidepressant are especially useful in the treatment of chronic pain conditions, most of the work about its mechanism of action has been made on acute pain tests. The present study was aimed at studying the role played by noradrenergic and opioidergic influences on the antinociceptive activity of subchronically administered clomipramine in the formalin test (a tonic pain model) in rats. Clomipramine produced antinociception after 7 days, administration (2.5 mg/kg/day), an effect equivalent to that obtained by acute morphine (5 mg/kg). The antinociceptive effect of clomipramine was inhibited by the following: nonspecific blocking of alpha₁-and alpha₂-adrenoceptors by phentolamine, specific blocking of alpha₁-adrenoceptors by prazosin; stimulation of alpha₂ receptors by clonidine; and blocking of the opioid receptors by naloxone. Blocking the alpha₂-receptors with yohimbine did not antagonize the effect of clomipramine. These results suggest that clomipramine produces antinociception in this test, partly via the participation of the endogenous opioid system and partly by further activating or potentiating previously activated noradrenergic pathways which are involved in the control of pain information.     

Use of the microorganism Bacillus stearothermophilus as a model to evaluate toxicity of the lipophilic environmental pollutant endosulfan

Microorganisms are very powerful tools for the supply of information about the toxic effects of lipophilic compounds, since an impairment of cell growth usually occurs as a result of perturbations related, in most cases, with the partition of toxicants in membranes. The thermophilic eubacterium Bacillus stearothermophilus has been used as a model system to identify α- and β-endosulfan interactions with the membrane possibly related with the insecticide toxicity. Two approaches have been pursued: (a) bacterial growth is followed and the effects of endosulfan isomers determined; (b) biophysical studies with the fluorescent fluidity probe 1,6-diphenyl-1,3,5-hexatriene (DPH) were performed to assess the effects of α- and β-endosulfan on the organization of the membrane lipid bilayer. The effects on growth were quantitatively evaluated by determination of growth parameters, namely the lag phase, the specific growth rate and the cell density reached by cultures in the stationary phase. Growth inhibition by α and β-endosulfan dependent on the concentration is diminished or removed by the addition of 2.5 m Ca²⁺ to bacterial cultures. Fluorescence DPH polarization consistently showed opposite effects of Ca²⁺ and α- and β-endosulfan on the physical state of bacterial polar lipid dispersions.     

Tamoxifen induces ultrastructural alterations in membranes of Bacillus Stearothermophilus

Tamoxifen (TAM), a non-steroid antiestrogen, is the mostly used drug for chemotherapy and chemoprevention of breast cancer. However, the mechanisms by which TAM inhibits cell proliferation in breast cancer are not fully understood. TAM strongly incorporates in biomembranes and a variety of effects have been assigned to biophysical and biochemical interactions with membranes. Therefore, a better understanding of the physicochemical basis of interaction of TAM with biomembranes is essential to elucidate the molecular mechanisms of action. A strain of Bacillus stearothermophilus has been used as a model to clarify the interaction of TAM with the cell membrane. TAM effects on the ultrastructure of membranes of this bacterium were evaluated by electron microscopy. Important ultrastructural alterations were observed in B. stearothermophilus treated with TAM, namely change in the geometry of the membrane profile from asymmetric to symmetric, disaggregation of ribosomes, coagulation of the cytoplasmic matrix, occurrence of mesossomes, appearance of fractures in membranes and the alteration of the ultrastructure of cell wall. These ultrastructural alterations confirm that TAM is a membrane-active drug and that membrane damage may be involved in molecular mechanisms of cell death induced by this drug.     

Tamoxifen induces ultrastructural alterations in membranes of Bacillus Stearothermophilus.

Tamoxifen (TAM), a non-steroid antiestrogen, is the mostly used drug for chemotherapy and chemoprevention of breast cancer. However, the mechanisms by which TAM inhibits cell proliferation in breast cancer are not fully understood. TAM strongly incorporates in biomembranes and a variety of effects have been assigned to biophysical and biochemical interactions with membranes. Therefore, a better understanding of the physicochemical basis of interaction of TAM with biomembranes is essential to elucidate the molecular mechanisms of action. A strain of Bacillus stearothermophilus has been used as a model to clarify the interaction of TAM with the cell membrane. TAM effects on the ultrastructure of membranes of this bacterium were evaluated by electron microscopy. Important ultrastructural alterations were observed in B. stearothermophilus treated with TAM, namely change in the geometry of the membrane profile from asymmetric to symmetric, disaggregation of ribosomes, coagulation of the cytoplasmic matrix, occurrence of mesossomes, appearance of fractures in membranes and the alteration of the ultrastructure of cell wall. These ultrastructural alterations confirm that TAM is a membrane-active drug and that membrane damage may be involved in molecular mechanisms of cell death induced by this drug.     

Integration of bilateral whisker stimuli in rats: role of the whisker barrel cortices.

Recently, we demonstrated that neural responses within the whisker region of the primary somatosensory cortex (SIw) of rats are profoundly influenced by the spatiotemporal attributes of ipsilateral, as well as contralateral, whisker stimuli. As inactivation of one SIw eliminates in the intact SIw both ipsilaterally evoked responses and the influence of ipsilateral stimulation on contralaterally evoked activity, we proposed that interhemispheric interactions between the SIws may be important for integrating bilateral whisker information. To test whether rats can recognize the bilateral nature of a whisker stimulus, we developed a tactile discrimination task that required rats to conjointly determine distances to a left and a right discriminandum as equidistant or non-equidistant using only their facial whiskers. All rats trained in this task achieved performance levels indicative of an ability to integrate bilateral whisker information. Testing during unilateral, as well as bilateral, inactivation of the SIws indicated that rats rely on both SIws for detecting the bilateral nature of a whisker stimulus. Rats were unable to perform the task without both sets of whiskers, a fact that indicates that the whiskers (and not other modalities) were used to perform this task. The findings presented here indicate that rats can solve a task that requires the conjoint detection of left and right whisker-mediated distance information and implicate the SIws as central to this ability.     

Ossifying fibromyxoid tumor of soft parts

Ossifying fibromyxoid tumors (OFT) of soft parts are very rare neoplasms recently described by Enzinger et al. (1). They usually present as well-circumscribed, slow-growing, asymptomatic subcutaneous masses. A characteristic finding is a fibrous capsule and an incomplete peripheral shell of mature bone. Although most cases behave as benign tumors, a high rate of local recurrences have been described. We describe a 43-year-old male with a perianal subcutaneous tumor of 10 years evolution. The histopathology was compatible with OFT. Due to the subcutaneous location of OFF, both the dermatologist and dermatopathologist need to know about this rare tumor.     

Lactoperoxidase and human airway host defense

The lactoperoxidase (LPO) antibiotic system is a well-characterized component of mammary and salivary gland secretions. Because LPO has been shown to function in ovine airways, human airway tissue and secretions were examined for the presence of LPO and its substrate, the anion thiocyanate (SCN-). In addition, human airway secretions were tested for LPO-mediated antibacterial activity, and LPO's activity was assessed against some human airway pathogens. The data showed that normal human airway secretions contained LPO enzyme activity (0.65 +/- 0.09 microg/mg secreted protein; n = 17), and Western blots of secretions demonstrated bands of the expected sizes for LPO. LPO mRNA was detected in trachea by sequencing PCR-amplified cDNA. SCN-, LPO's substrate, was present in undiluted airway secretions at concentrations sufficient for LPO catalysis (0.46 +/- 0.19 mM; n = 8), and diluted secretions contained antibacterial activity with LPO-like properties. Immunocytochemistry localized LPO to submucosal glands in human bronchi. Finally, as expected based on the known antibacterial spectrum of the LPO system, airway secretions showed LPO-dependent activity against Pseudomonas aeruginosa. In addition, the airway LPO system was shown to be effective against Burkholderia cepacia and Haemophilus influenzae. Thus, a functional LPO system exists in human airways and may contribute to airway host defense against infection.