Alterations to the contents of plasma membrane structural lipids are associated with structural changes and compartmentalization in platelets in hypertension.

Arterial hypertension (HTN) can lead to serious organ damage. Several mechanisms have been implicated in the pathogenesis of HTN including constitutive activation of platelets, which increases the risk of aggregation and clot formation. We recently demonstrated the plasma membranes of platelets from patients with HTN exhibit modified structural and physicochemical properties; Raman and Fourier transform infrared by attenuated total reflectance (FTIR-ATR) spectroscopy also indicated lipid content and protein structure alterations. This study aimed to precisely quantify the constituents of the main structural phospholipids and cholesterol in the plasma membranes of platelets from patients with HTN and normotensive individuals. We also assessed the consequence of these alterations on platelet structure and function. Liquid chromatography coupled to triple quadrupole mass spectrometry revealed the plasma membranes of HTN platelets contained less cholesterol and phosphatidylcholine, more phosphatidylserine and phosphatidylethanolamine and had similar sphingosine contents. Atomic force microscopy revealed HTN platelets exhibited increased surface roughness and more pleats. Transmission electron microscopy revealed diminution of the internal membranous structures in HTN platelets. Our findings strongly suggest plasma membrane lipid content alterations-including cholesterol depletion-occur in HTN, and these alterations may induce morphological and physiological abnormalities that participate in the functional changes associated with hypertension.

Aqueous root extracts from Mimosa albida Humb. & Bonpl. ex Willd display antinociceptive activity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: In this work, we study whether aqueous extracts from the roots of Mimosa albida Humb. & Bonpl. ex Willd, a plant known in the Highlands of Chiapas, Mexico as "Lotóm chíx" are endowed with both antinociceptive and anxiolytic effects. MATERIALS AND METHODS: ICR mice were systemically treated with aqueous extracts from Mimosa albida and the reference compounds (diazepam, dipyrone and/or fentanyl) and their behavior was evaluated in several behavioral tests. RESULTS: Administration of aqueous extracts from the roots of Mimosa albida resulted in a reduction of the nociception elicited in mice by both the hot plate (12.5, 25 and 50 mg/kg; i.p.) and the acetic acid-induced writhing (25 and 50 mg/kg; i.p.) tests. No effects were however observed both in the elevated plus-maze and hole board test (3.2, 12.5 and 25 mg/kg; i.p.). In contrast, both locomotion (open field test) and motor coordination (rotarod test) were affected at doses (50, 100 y 200 mg/kg; i.p.) higher than those having antinociceptive effects. CONCLUSION: These data suggest that in mice the systemic administration of low doses of aqueous extracts from the roots of Mimosa albida results in antinociceptive effects in several models of pain through mechanisms that do not involve the opioid system pathway. These results support the ethnopharmacological use of Mimosa albida in popular medicine.

Distribution of dopamine D(2)-like receptors in the rat amygdala and their role in the modulation of unconditioned fear and anxiety.

Amygdaloid dopamine D(2) receptors play an important role in the modulation of fear/anxiety. Their topographical distribution within the amygdala is however unclear, and their role in unconditioned fear/anxiety remains largely unknown. The aim of this paper was to study the intra-amygdaloid distribution of D(2) receptors and to ascertain their role in unconditioned anxiety. Chemical anatomical studies in the rat, using D(2) and D(3)in situ hybridization, quantitative receptor autoradiography with either [(3)H]raclopride or [(125)I]sulpiride, and D(2)-like immunocytochemistry showed that the highest density of dopamine D(2) receptors is present in the central amygdaloid nucleus, particularly within its latero-capsular division, in which a D(2) but not a D(3) mRNA signal was observed. However, although at considerably reduced densities dopamine D(2) receptors were also found in other locations within the amygdala, including the basolateral nucleus. Behaviorally, the infusion of raclopride (0.75-4 µg/side) in the area of the central amygdaloid nucleus resulted at low doses in the appearance of anxiogenic-like effects in the Shock-Probe Burying test, whereas no effects of raclopride treatment were found at any dose in the Elevated Plus-Maze and the Open-Field test. Our results indicate that amygdaloid dopamine D(2)-like receptors have a topographically differentiated distribution within the rat amygdala, the major location being in the central amygdaloid nucleus. D(2)-like receptors play a role in the modulation of anxiety responses involving a potential differential function of D(2)-like receptors in the central amygdaloid nucleus versus the basolateral amygdaloid nucleus.

Molecular and catalytic properties of the aldehyde dehydrogenase of Gluconacetobacter diazotrophicus, a quinoheme protein containing pyrroloquinoline quinone, cytochrome b, and cytochrome c.

Several aldehyde dehydrogenase (ALDH) complexes have been purified from the membranes of acetic acid bacteria. The enzyme structures and the chemical nature of the prosthetic groups associated with these enzymes remain a matter of debate. We report here on the molecular and catalytic properties of the membrane-bound ALDH complex of the diazotrophic bacterium Gluconacetobacter diazotrophicus. The purified ALDH complex is a heterodimer comprising two subunits of 79.7 and 50 kDa, respectively. Reversed-phase high-pressure liquid chromatography (HPLC) and electron paramagnetic resonance spectroscopy led us to demonstrate, for the first time, the unequivocal presence of a pyrroloquinoline quinone prosthetic group associated with an ALDH complex from acetic acid bacteria. In addition, heme b was detected by UV-visible light (UV-Vis) spectroscopy and confirmed by reversed-phase HPLC. The smaller subunit bears three cytochromes c. Aliphatic aldehydes, but not formaldehyde, were suitable substrates. Using ferricyanide as an electron acceptor, the enzyme showed an optimum pH of 3.5 that shifted to pH 7.0 when phenazine methosulfate plus 2,6-dichlorophenolindophenol were the electron acceptors. Acetaldehyde did not reduce measurable levels of the cytochrome b and c centers; however, the dithionite-reduced hemes were conveniently oxidized by ubiquinone-1; this finding suggests that cytochrome b and the cytochromes c constitute an intramolecular redox sequence that delivers electrons to the membrane ubiquinone.

Effects of REM sleep deprivation on the d-amphetamine-induced self-mutilating behavior.

It is well known that self-mutilating behavior (SMB) is developed in rats and humans during the daily treatment with d-amphetamine. Accordingly, in this work it was found that the daily treatment with 7.5 mg/kg d-amphetamine induced in rats a progressive appearance of SMB. Lower doses (5.0 mg/kg) were uneffective and higher doses (10 mg/kg) produced a pattern of SMB in which the mutilation induced at the beginning of the d-amphetamine administration disappears completely as the treatment progresses. Interestingly, it was also found that REM sleep deprivation (48 h) potentiated significantly the SMB induced by the daily administration of 7.5 mg/kg d-amphetamine, and to lesser extent, the SMB induced by the daily treatment with 10 mg/kg d-amphetamine. R(+)-SCH-23390 a D1 dopamine (DA) receptor antagonist blocked completely or abolished the SMB induced by 7.5 mg/kg d-amphetamine in REM sleep deprived rats while (+/-)-sulpiride a D2 DA receptor antagonist had only a partial blocking effect. Haloperidol a D1/D2 DA receptor antagonist behaved as a D1 antagonist. Our results indicate that REM sleep deprivation enhances the SMB induced by the daily administration of d-amphetamine and suggest the involvement of D1 DA receptors in the mechanism underlying the SMB. A role of REM sleep deprivation is also suggested in the appearance of self-mutilating episodes in d-amphetamine addicts.

Cholecystokinin-8 increases K(+)-evoked [3H] gamma-aminobutyric acid release in slices from various brain areas.

[3H] gamma-Aminobutyric acid (GABA) release was studied in rat brain slices in the absence or presence of cholecystokinin-8 (CCK-8). [3H]GABA release under the conditions used was Ca(2+)-dependent and insensitive to the presence of the glial uptake blocker beta-alanine. While the basal release of [3H]GABA was not affected by CCK-8, the K(+)-stimulated release of [3H]GABA was significantly enhanced by 300 nM of CCK-8 in the caudate putamen, the substantia nigra, the hippocampal formation and the parietofrontal cortex. In the cerebral cortex the CCK-8 enhancement of [3H]GABA release was concentration-dependent and abolished by the CCKB receptor antagonists PD135,158 (1.0 nM) and L-365,260 (100 nM). A significant counteraction of the CCK-8 action was also found with the CCKA receptor antagonist L-364,718 (100 nM) but only in concentrations at which both CCKA and CCKB receptors are blocked. No CCK-8 effects on [3H]GABA release were observed when tetrodotoxin was superfused 5 min before the K(+)-induced [3H]GABA release. It is suggested that the enhancing actions of CCK-8 on K(+)-stimulated [3H]GABA release is mainly related to an activation of CCKB receptors.

[Pulmonary aspergillosis]. / Aspergilosis pulmonar.

We report a 15-year-old male with bronchial asthma since five years old, unresponsive to treatment; at age 12 a diagnosis of pulmonary tuberculosis was made and treated with several drugs. He was referred to our hospital because of hemoptysis. A diagnosis of aspergillosis in the aspergilloma form was made; after, a left upper lobectomy showed the invasive form; later he presented recurrent obstructive respiratory problems, secondary to the allergic form. Serum IgE was elevated, lowering after treatment with corticoids; simultaneously he had clinical improvement. Treatment was discontinued when clinically asymptomatic and serum IgE was normal. Diagnostic route and treatment are discussed.