Biological evaluation of chalcones and analogues as hypolipidemic agents

In order to evaluate the anti-hyperlipidemic effect of synthetic chalcones and some analogues, nineteen compounds with different substituents in both rings were synthesized and hypolipidemic activities were measured in vivo using Triton WR1339 acute and hypercaloric chronic assays. 4',4-dichlorochalcone, 3',4',4-trichlorochalcone, and 4'-chlorochalcone gave an excellent decrease in serum total cholesterol and triglycerides in the acute assay. These compounds also showed significant anti-lipidemic activity in the chronic assay.     

Autonomic and respiratory responses to microinjection of ATP into the intermediate or caudal nucleus tractus solitarius in the working heart-brainstem preparation of the rat

1. Activation of peripheral chemoreceptors with KCN in the working heart-brainstem preparation from young male Wistar rats (70-90 g) increases phrenic (PNA; +105 +/- 18%) and thoracic (tSNA; +44 +/- 6%) sympathetic nerve activity compared with baseline and reduces heart rate (HR; from 377 +/- 27 to 83 +/- 6 b.p.m.). 2. Microinjections of increasing doses of ATP (1, 5, 25, 100 and 500 mmol/L; n = 7) into the intermediate nucleus tractus solitarius (NTS) produced a dose-dependent reduction in PNA (from -6 +/- 3 to -82 +/- 1%) and in HR (from -12 +/- 4 to -179 +/- 47 b.p.m.). Microinjections of ATP into the intermediate NTS also produced a reduction in tSNA (from -3 +/- 3 to -26 +/- 5%), which was not dose dependent. 3. Microinjections of ATP into the caudal NTS (n = 5) produced a dose-dependent increase in PNA (from 0.2 +/- 3 to 115 +/- 27%) and minor changes in HR and tSNA, which were not dose dependent. 4. The data show that microinjection of ATP into distinct subregions of the NTS produces different respiratory and autonomic responses and suggest that ATP in the caudal NTS is involved in the respiratory but not in the sympathoexcitatory component of the chemoreflex.     

Antifungal activity and studies on mode of action of novel xanthoxyline-derived chalcones

Chalcones and chalcone-like compounds, most of them new ones, prepared by base-catalyzed condensation of appropriate aldehydes and xanthoxyline, were tested for antifungal properties against a panel of yeasts, hialohyphomycetes as well as dermatophytes with the agar dilution assay. Results indicate that neither the sole presence of a "xanthoxyline-like" substitution pattern nor a 2'-OH substituent on ring A are sufficient for these compounds to have antifungal properties. The chalcone 3-(2-chlorophenyl)-1-(2'-hydroxy-4',6'-dimethoxyphenyl)prop-2-en-1-one, with a Cl atom in the ortho position of benzene ring B showed the best antifungal activity against standardized strains of Trichophyton rubrum (MIC = 12.5 microg/mL) and inhibited all of the ten clinical isolates of T. rubrum tested (MIC at which 50 % [MIC(50)] and 90 % [MIC(90)] of the isolates were inhibited = 12.5 and 25 microg/mL). Regarding its mode of action, the Neurospora crassa assay showed a blotchy appearance in the inhibition halo produced by this chalcone, strongly suggesting that it could act by inhibiting the fungal cell wall. This chalcone seems to be an hyphal malformation inducer, since a clear curling of the hypha was observed in this hazy zone at a magnification of x 400. This work strongly contributes to the knowledge of the antifungal properties of hydroxy-chalcones.     

High altitude exposure impairs sleep patterns, mood, and cognitive functions

This work evaluated the importance of sleep on mood and cognition after 24 h of exposure to hypoxia. Ten males, aged 23–30 years, were placed in a normobaric chamber simulating an altitude of 4,500 m. Sleep assessments were conducted from 22:00–6:00; all mood and cognitive assessments were performed 20 min after awakening. The assessments were conducted in normoxic conditions and after 24 h of hypoxia. Sleep was reevaluated 14 h after the start of exposure to hypoxic conditions, and mood state and cognitive functions were reevaluated 24 h after the start of exposure to hypoxic conditions. Hypoxia reduced total sleep time, sleep efficiency, slow‐wave sleep, and rapid eye movement. Depressive mood, anger, and fatigue increased under hypoxic conditions. Vigor, attention, visual and working memory, concentration, executive functions, inhibitory control, and speed of mental processing worsened. Changes in sleep patterns can modulate mood and cognition after 24 h.     

Impact of effective valvotomy in mitral stenosis on pulmonary venous flow pattern

AIMS: Transesophageal Doppler echocardiography (TEE) is a useful tool to investigate pulmonary venous flow (PVF) velocity, which is altered in patients with mitral stenosis (MS). This study used TEE to analyze the variations in the PVF pattern after successful valvar dilatation in MS patients. METHODS/RESULTS: A total of 15 MS patients, mean age 27.2 years, underwent effective percutaneous balloon valvotomy (PBV). All were submitted to TEE before and after PBV. TEE assessed systolic (SPFV) and diastolic (DPFV) peak flow velocities and their ratio (SPFV/DPFV), time-velocity integrals (STVI and DTVI) and their ratio, and diastolic flow deceleration (DFD). Valvotomy yielded statistically significant increases (P < or = 0.05) in the SPFV: increase on average by 67% and STVI by 120%, as well as in the diastolic component: increased on average by 35%, DTVI by 33%, and DFD by 75%. CONCLUSION: TEE demonstrated that PBV induced a global increase in velocities of PVF, probably related to improvement of left atrial emptying.     

New antinociceptive agents related to dihydrosphingosine

The main objective of this study was to evaluate the antinociceptive activity of three ethylenediamine derivatives and three β-aminoethanol lipidic derivatives structurally related to dihydrosphingosine. These derivatives were selected on the basis of previous results from in vitro and in vivo anti-inflammatory studies. For all of the assayed compounds, an intraperitoneal dose of 3 mg/kg caused pronounced pain inhibition as measured by the acetic acid-induced writhing model in mice. Compounds 3 and 6 demonstrated strong antinociceptive activity at doses as low as 1 mg/kg and proved to be considerably more potent than the common nonsteroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA) and acetaminophen (ACE). We further analyzed these compounds using the capsaicin- and glutamate-induced pain tests. Compounds 3 and 6 also exhibited considerable antinociceptive effects under these conditions, but their inhibitory effects in the formalin test were less pronounced. The exact mechanism of action for these compounds has yet to be established. However, based the results from a hot-plate test, it can be stated that these new drugs do not interact with the opioid system.     

Effect of Er:YAG and Diode lasers on the adhesion of blood components and on the morphology of irradiated root surfaces

OBJECTIVE: The aim of this study was to evaluate in vitro, by scanning electron microscopy (SEM), the adhesion of blood components on root surfaces irradiated with Er:YAG (2.94 microm) and GaAlAs Diode (808 nm) lasers and the effects on the morphology of irradiated root surfaces. METHODS: One hundred samples of human teeth were obtained. They were previously planed and scaled with manual instruments and divided into five groups of 20 samples each: G1 (control group) - absence of treatment; G2--Er:YAG laser (7.6 J/cm2); G3--Er:YAG laser (12.9 J/cm2); G4--Diode laser (90 J/cm2) and G5--Diode laser (108 J/cm2). After these treatments, 10 samples of each group received a blood tissue but the remaining 10 did not. After laboratory treatments, the samples were obtained by SEM, the photomicrographs were analysed by the score of adhesion of blood components and the results were statistically analysed (Kruskall-Wallis and Mann-Whitney test). RESULTS: In relation to the adhesion of blood components, the study showed no significant differences between the control group and the groups treated with Er:YAG laser (p = 0.9633 and 0.6229). Diode laser radiation was less effective than control group and Er:YAG laser radiation (p < 0.01). CONCLUSIONS: None of the proposed treatments increased the adhesion of blood components in a significant way when compared to the control group. Although the Er:YAG laser did not interfere in the adhesion of blood components, it caused more changes on the root surface, whereas the Diode laser inhibited the adhesion.     

Periodontal plastic surgery associated with treatment for the removal of gingival overgrowth

BACKGROUND: Excisional biopsies of gingival overgrowths, performed with safety margins, frequently result in mucogingival defects. These defects may produce esthetic problems and increase the chances of dentin hyperesthesia and its possibility of hindering oral hygiene. METHODS: Two clinical cases are reported in which gingival overgrowths were removed by excisional biopsy, resulting in unsightly defects. The first clinical case presents an invasive approach for the treatment of a recurrent pyogenic granuloma in the anterior maxilla, and the second depicts a complete removal of a peripheral odontogenic fibroma in the posterior maxilla. In both situations, the soft-tissue defects were repaired by periodontal plastic surgery, including a laterally positioned flap and a coronally positioned flap, respectively. RESULTS: Periodontal plastic surgery successfully restored the defects that resulted from biopsies, and no recurrence has been noticed in the 5-year postoperative follow-up period. CONCLUSIONS: The combination of biopsy and periodontal plastic surgery in a one-step procedure seems to be suitable to remove gingival overgrowths in most areas of the mouth, regardless of esthetic significance. Such procedures seem to restore gingival health, encourage healing, and create both esthetics and function in the excised area.     

Unravelling the cardiovascular effects induced by α‐terpineol: A role for the nitric oxide–cGMP pathway

1. α‐Terpineol is a monoterpene found in the essential oils of several aromatic plant species. In the present study, we investigated the mechanisms underlying the cardiovascular changes induced by α‐terpineol in rats. 2. In normotensive rats, administration of α‐terpineol (1, 5, 10, 20 and 30 mg/kg, i.v.) produced a dose‐dependent hypotension (?10 ± 3, ?20 ± 8, ?39 ± 16, ?52 ± 21 and ?57 ± 23 mmHg, respectively; n = 5) followed by tachycardia. The hypotensive responses to 1, 5, 10, 20 and 30 mg/kg, i.v., α‐terpineol were significantly attenuated following the administration of N^G‐nitro‐l‐ arginine methyl ester (l ‐NAME; 20 mg/kg, i.v.; ?2 ± 1, ?5 ± 2, ?7 ± 3, ?22 ± 9 and ?22 ± 10 mmHg, respectively; P < 0.05; n = 5). 3. In 10 μmol/L phenylephrine (PE)‐precontracted mesenteric artery rings, α‐terpineol (10^?12 to 10^?5 mol/L) caused a concentration‐dependent relaxation (maximum relaxation 61 ± 6%; n = 7). After removal of the endothelium, the vasorelaxation elicited by α‐terpineol was attenuated (maximum relaxation 20 ± 1%; P < 0.05; n = 7). In addition, vasorelaxation induced by α‐terpineol in rings pretreated with 100 or 300 μmol/L l ‐NAME, 30 μmol/L hydroxocobalamin or 10 μmol/L 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one was attenuated (maximum relaxation 18 ± 3, 23 ± 3, 24 ± 7 and 21 ± 1%, respectively; n = 6; P < 0.05). 4. Furthermore, in a rabbit aortic endothelial cell line, 10^?6, 10^?5 and 10^?4 mol/L α‐terpineol induced concentration‐dependent increases in nitric oxide (NO) levels (12 ± 6, 18 ± 9 and 34 ± 12%Δ fluorescence, respectively; n = 3). 5. In conclusion, using combined functional and biochemical approaches in the present study, we were able to demonstrate that α‐terpineol‐induced hypotension and vasorelaxation are mediated, at least in part, by the endothelium, most likely via NO release and activation of the NO–cGMP pathway.