Protective role of free and quercetin-loaded nanoemulsion against damage induced by intracerebral haemorrhage in rats.

Intracerebral haemorrhage (ICH) is a worldwide public health problem. Experimental studies have shown that oxidative stress plays an important role in the pathogenesis of ICH and could represent a target for its treatment. However, the blood-brain barrier is an obstacle to be overcome, as it hampers the administration of compounds to the central nervous system. In this study, we compared the effects of a quercetin-loaded nanoemulsion (QU-N) with the free form of the drug (QU-SP) in a collagenase-induced ICH rat model. Quercetin (QU) is a polyphenol that has an antioxidant effect in vitro, but due to its high lipophilicity, it has low bioavailability in vivo. In this study, animals submitted or not to ICH were treated with a single intraperitoneal QU dose (free or nanoemulsion) of 30 mg kg(-1). Motor assessment was evaluated by the open field, foot fault and beam walking behavioural tests. 72 h after surgery the haematoma size was evaluated and biochemical measurements were performed. Animals treated with QU-N had a significant improvement in the beam walking and open field tests. Also, QU-N was able to reduce the size of the haematoma, preserving the activity of glutathione S-transferase (GST), increasing GSH content, and the total antioxidant capacity. QU-SP recovered locomotor activity and increased the GSH content and the total antioxidant capacity. Thus, it can be observed that QU presented antioxidant activity in both formulations, but the incorporation into nanoemulsions increased its antioxidant effect, which was reflected in the improvement of the motor skills and in the haematoma size decrement. These results suggest that the nanoemulsion containing QU developed in this study could be promising for future studies on treatments for ICH.

[Vacuum-assisted closure of nonhealing wounds in head and neck reconstructive surgery]. / Vakuumassistierte Therapie zur Wundbehandlung im Kopf-Hals-Bereich.

Chronic wounds are characterized by slow or nonexistent wound healing. Usually their treatment is expensive. Therefore new concepts in management are of interest in order to reduce treatment time and costs. One option is vacuum sealing. The concept of topical negative pressure is not new, and many chronic nonhealing wounds could be closed successfully with the help of vacuum sealing. Until now, there has been no documented case of vacuum sealing in head and neck reconstructive surgery. Our case shows the effectiveness of a vacuum-assisted device in successful closure of a chronic nonhealing wound in this region.

[Use of a screening device for sleep apnea in clinical practice]. / Der klinische Einsatz eines Schlafapnoescreeners in der Praxis.

About 2-4% of adults suffer from obstructive sleep apnea (OSA), which is the most common sleep-related breathing disorder (SRBD). Repetitive obstructions of the upper airway mean that it is associated with hypertension and an elevated cardio- and cerebrovascular morbidity, which can be lowered by means of effective therapy. These patients cannot be treated correctly unless they are identified early in the course of the condition. Therefore, this study evaluated the use of the microMESAM screening device (known up to December 2005 as the "ApneaLink") in 61 patients in whom SRBD was suspected. The device proved reliable and practical in application.

[Hyperplastic scars and keloids: part II: Surgical and non-surgical treatment modalities]. / Hyperplastische Narben und Keloide: Teil II: Chirurgische und konservative Behandlungsmodalitäten.

Aberrant wound healing results in unsightly scarring, hypertrophic scarring, and keloid formation, causing functional and cosmetic deformities, discomfort, psychological stress, and patient dissatisfaction. Scar management, both surgical and non-surgical, continue to be important issues for the facial plastic surgeon. Many techniques for the management of hypertrophic scars and keloids have been proven through extensive use, but few are supported by prospective studies with adequate control groups. Several new therapies showed good results in small-scale trials, but these have not been repeated in larger trials with long-term follow-up. This article presents an overview of the available therapies and provides recommendations for the treatment of abnormal scarring. The recommendations focus on the management of hypertrophic scars and keloids. Strategies for the management of keloids and hypertrophic scars are of continuing interest and studies are necessary to understand the basic mechanisms causing aberrant wound healing. In addition, an overview of new developments in molecular wound management and gene therapy, as they relate to facial plastic surgery, is provided.

[Hyperplastic scars and keloids. Part I: basics and prevention]. / Hyperplastische Narben und Keloide. Teil I: Grundlagen und Prävention.

Aberrant wound healing results in unsightly scarring, hypertrophic scarring, and keloid formation, causing functional and cosmetic deformities, discomfort, psychological stress, and patient dissatisfaction. Scar prevention and management continue to be important issues for the facial plastic surgeon. This article presents an overview on the pathogenesis of a scar and of the different types of scars. Differences between keloids, hypertrophic scars and normal scars include distinct scar appearance, histologic morphology and cellular function in response to growth factors. Recent advances in our understanding of the wound healing process reveal possible causes for hypertrophic scars and keloids. This information might assist in the development of efficacious prevention and treatment for hypertrophic scar and keloid formation. This article also describes the strategies available for scar prevention. Recommendations focus on the management of hypertrophic scars and keloids.

[Finding the appropriate therapy with the help of sleep endoscopy]. / Mit der Schlafendoskopie zur richtigen Therapie.

Nasal continuous positive airway pressure (nCPAP) ventilation is the gold standard in the treatment of obstructive sleep apnea (OSA). For patients with CPAP-intolerance and for those tolerating the CPAP-mask but without success, surgical strategies are of growing interest. There are several surgical concepts which combine different surgical procedures on both the velopharyngeal and the retro-lingual section of the upper airway. The case presented here describes the failed CPAP-therapy in an OSAS-patient who tolerates the CPAP-mask. The apneas and hypopnoes could not be reduced by using the CPAP-mask, even more they increased under CPAP-ventilation. Performing a video-documented sleep-endoscopy of the upper airway (under physiological sleep patterns) the location of the obstruction could be identified. After performing a hyoid suspension in combination with a radiofrequency therapy of the base of tongue the apneas and hypopneas decreased. Only by using the sleep endoscopy the reason for the failed CPAP-therapy could be identified and therefore the surgical protocol succeed. To what extend the sleep video endoscopy becomes a standardized procedure in sleep labs warrants further investigations.

[Subjective outcome after multi-level surgery in sleep-disordered breathing]. / Subjektives Outcome der Mehretagenchirurgie bei schlafbezogenen Atemstörungen.

INTRODUCTION: Previous results showed the high effectiveness of our multi-level surgery concept based on the modified hyoid suspension for obstructive sleep apnea (OSA). This study was aimed at evaluating the discomforts and side-effects of this surgical concept. METHODS: Between November 2001 and June 2004, 102 patients with OSA and/or with laryngeal stenosis, who were all treated with a hyoid suspension in combination with surgery at the base of tongue, the soft palate or the nose, were included in the study. A questionnaire on discomfort and snoring was given to the patients. They were asked to answer the questions at the earliest 1 month after surgery. A reduction in snoring to a level which was tolerated by the bed-partner was regarded as success. RESULTS: Half of the patients needed analgesics until the 14th day after surgery, complained dysphagia until day 20 and had problems with their speech until day 30. However, 84% indicated that they would undergo surgery again; 94% reported a successful reduction in their snoring. CONCLUSION: Nearly all of the patients tolerated the discomforts and side-effects of our multi-level surgical concept. In combination with a reduction in snoring in 94% of all cases, this surgical concept was considered favorably by the patients.

[Snoring/sleep apnea--surgically curable]. / Schnarchen /Schlafapnoe--chirurgisch heilbar ?

INTRODUCTION: Obstructive sleep apnea (OSA) is characterized by nocturnal collapsing of the upper airways. Nasal continuous positive airway pressure (nCPAP) ventilation is the gold standard in the treatment of obstructive sleep apnea syndrome (OSAS). Long-term compliance rates do not exceed more than 60 to 70%. Alternative multi-level surgeries are of interest, combining procedures at the level of the base of tongue and the soft palate in order to stabilize the airway. Preliminary results suggested the hyoid suspension as one part of the multi-level surgery concept to be of high effectiveness. Therefore this study investigated the outcome of the hyoid suspension and compared it with the CPAP therapy. METHODS: Between March 2001 and February 2003, 66 patients with OSA were treated with a hyoid suspension in combination with surgeries at the base of tongue, the soft palate or the nose (always performed by the same surgeon). All patients underwent a pre- and postoperative polysomnography in the sleep lab. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Mean age was 52,1 years, the mean body mass index (BMI) was 28,04 kg/m(2). RESULTS: The mean apnea-hypopnea-index (AHI) was 38,9121,10/h before operation and 19,25+/-19,64/h after operation (p<0,0001). More statistically significant changes were found for the arousal index, the oxygen saturation and the ESS (p<0,05). After surgery 57,6% of the subjects (38/66) were regarded as cured (reduction of AHI > or =50% and below 15/h). Another 21,2% (14/66) improved (reduction of AHI >20%). Altogether 78,8% of the patients were counted as responders. CONCLUSION: Multi-level surgeries based on the hyoid suspension show the effectiveness of this concept. This surgical strategy could be equal to the CPAP mask, especially in cases of CPAP intolerance.

[Multi-level surgery for obstructive sleep apnea. Preliminary objective results]. / Multi-Level-Chirurgie bei obstruktiver Schlafapnoe. Erste objektive Ergebnisse.

BACKGROUND: Nasal continuous positive airway pressure (nCPAP) ventilation is the gold standard in the treatment of obstructive sleep apnea (OSA). Unfortunately nCPAP does not exceed long-term compliance rates of much more than 60 percent. Therefore, surgical strategies are of growing interest in this field. Today, so called multi-level surgeries are favored which combine at least one surgical procedure on both the velopharyngeal and the retrolingual section of the upper airway. The Mannheim concept combines at least one surgical procedure to the soft palate (UPPP or Uvulaflap) inclusive tonsillectomy and a hyoid suspension and/or a radiofrequency procedure on the base of tongue. METHODS: In between July 2000 and February 2003, 139 patients with OSA were included in the protocol. By now 46 patients finished the follow-up. Mean age was 51.9 years, the mean body mass index was 28.5 kg m (- 2). All patients underwent as well preoperatively as postoperatively a fully attended polysomnography in the sleep lab using standard criteria. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). RESULTS: Before surgery the mean apnea-hypopnea-index (AHI) was 36.5 +/- 22.2, the mean ESS score was 10.4. Postoperatively the mean AHI decreased to 24.9 +/- 21.6 (p < 0.01) and the mean ESS score to 7.1 (p < 0.05). After surgery 39.1 % of the subjects were regarded as cured (reduction of AHI > or = 50 % and below 15). Another 30.4 % were substantially improved (reduction of AHI > 20 %). Altogether 69.6 % of the patients were counted as responders. Cure rates decreased with increasing AHI and BMI. The hyoid suspension showed a positive effect on the treatment success. CONCLUSIONS: The presented concept shows inferior success rates than other more invasive concepts. This might be due to the abandonment of the mandibular osteotomy with genioglossus advancement.

Fish Balistes capriscus skin extract-induced relaxation in mesenteric arterial bed of rat.

The vasorelaxing activity of the aqueous extract of fish Balistes capriscus skin (AEBc) on mesenteric arterial bed (MAB) of rats was studied. The bolus injections of AEBc (bolus of 5.1, 10.2, 20.5, and 41.1mg) significantly inhibited, in a concentration-dependent manner, the maximal contractile response induced by methoxamine (30 microM) in MAB. The vasodilatation action of AEBc is not mediated through beta-adrenoceptors or cyclo-oxigenase, since it was not affected by propranolol (20 microM) or diclofenac sodium (3 microM). The vasodilator response induced by subsequent addition of AEBc Balistes capriscus in bolus was significantly reduced in water infusion for endothelium removal. Treatment with an inhibitor of NO synthase (L-NAME, 10 microM) decreased AEBc effect. The guanylate cyclase inhibitor methylene blue (MB, 100 microM) had no significant effect on AEBc-induced vasodilatation. These results suggest that the vasorelaxing effect of AEBc is mediated by endothelium-dependent (NO/EDRF) and endothelium-independent neurally induced vasorelaxation from nonadrenergic and noncholinergic nerves (NO).

Distortion product otoacoustic emissions in human hypercholesterolemia.

Epidemiological and experimental studies suggest that hypercholesterolemia promotes the development of sensorineural hearing loss; however, the underlying cellular pathomechanism remains obscure. In the present study, 20 healthy subjects and 20 patients with familial hypercholesterolemia were compared with respect to their hearing function. None of the 40 persons reported any history of hearing disorder. In accordance with this subjective impression, mean hearing thresholds were within the normal, age-dependent ranges in both groups. In contrast, the single-generator distortion product otoacoustic emissions (sgDPOAE) were reduced at and above 4 kHz. Input-output functions of DPOAE could be subdivided into three groups: (i) normal, with unity slope at low intensities and slope less than unity (0.24+/-0.07 dB/dB at higher intensities; (ii) pathologic, described by a single straight line; (iii) ill-defined, with data usually indistinguishable from the background noise level. The ill-defined DPOAE behavior was only found in patients with hypercholesterolemia; namely, for 25% of patients at f(2)=1.5 kHz and for 50% at f(2)=4 kHz. Patients belonging to the pathologic and ill-defined DPOAE groups had significantly (P<0.05) higher total serum cholesterol and LDL-cholesterol levels compared with subjects from the normal DPOAE group. While hearing thresholds of patients with ill-defined growth functions were not statistically different from those of normal subjects, speech scores were significantly reduced in these cases. The data imply that nonlinear mechanical processes in the cochlea are compromised in hypercholesterolemic patients.

Immunoblot studies in birch pollen-allergic patients with and without fruit hypersensitivity: part I: antibody pattern for birch pollen extract.

About 40-70% of birch pollen allergic patients show allergic symptoms after ingesting or handling raw fruits. Several investigations have indicated a partial immunological identity between birch pollen and stone fruit. To further clarify this association, we investigated 59 patients with allergic symptoms (conjunctivitis, rhinitis, and asthma during the birch pollen season) and 18 nonatopic controls by skin prick test (SPT) and RAST with birch pollen, fresh apple, cherry, and peach as well as freshly prepared fruit extracts. According to a questionnaire dealing with symptoms after ingestion of raw fruits, the subjects were divided into groups with (35 FH+) and without (24 FH-) fruit hypersensitivity. IgE, IgG, IgG1, IgG4, IgA, and IgM binding patterns to birch pollen extracts were performed with 33 sera (12 FH+, 11 FH-, and 10 nonatopic controls) using the immunoblot-technique. Patients with FH+ expressed a significantly stronger sensitization to birch pollen than patients without FH-, as measured by RAST and SPT. Native fruits induced stronger SPT reactions than fruit extracts, and patients with FH+ showed a significantly higher skin index with all fruits and fruit extracts tested. Specific IgE, IgG, IgG1, IgG4, IgM and IgA to birch pollen extracts could be detected by immunoblot in all groups, albeit with different frequencies and intensities. From this data we conclude that fruit hypersensitivity is related more to the 17 kd and 67-85 kd than to the 26-28 kd or 36 kd protein bands of the birch pollen extract. The relationship of specific IgE > IgG > IgM to a single protein band seems to be associated with the development of symptomatic type I allergy.

Immunoblot studies in birch pollen-allergic patients with and without fruit hypersensitivity: part II: antibody pattern for fruit extracts.

Patients allergic to birch pollen also exhibit more hypersensitivity reactions to fresh fruits and vegetables than do patients allergic to other pollens. Several investigations have indicated a possible partial immunological identity between birch pollen and fruits. To study this, 23 birch pollen-allergic patients 12 with (FH+) and 11 without (FH-) fruit hypersensitivity and 10 nonatopic controls were examined with self-prepared apple-peel, cherry, and peach extracts by immunoblotting. The self-prepared extracts were characterized by histamine release studies with 20 FH+ birch pollen-allergic patients. Specific IgE, IgG, IgG1, IgG4, IgA, and IgM binding patterns of the fruit extracts presented an individual distribution with at least 1-3 IgE bands at varying molecular weight locations. The FH+ group expressed intense IgE binding to the different extracts compared to the FH- group, and even the control group showed all immunoglobulin classes, though different frequencies and intensities compared to the allergic groups. It seemed that the specific IgE > IgG > IgM relation to a single antigen is important for distinguishing between symptomatic and asymptomatic persons. With this hypothesis we found most IgE with less IgG binding to apple-peel in the region of 22-28 kd and 43-56 kd, cherry: 15-25 kd and 72- > 90 kd and peach 35-41 kd and 66-76 kd, suggesting that these proteins might be important for cross-reactivity with birch pollen and developing fruit hypersensitivity.

Endothelium-dependent vasorelaxing activity of aqueous extracts of Ilex paraguariensis on mesenteric arterial bed of rats.

The effects of aqueous extracts of Ilex paraguariensis leaves (AEIp) were studied. Mesenteric arterial bed (MAB), precontracted by methoxamine with or without intact endothelium, was mounted on a tissue bath and exposed to plant extracts (bolus). The bolus injections of AEIp (300-1050 microg) significantly inhibited, in a concentration-dependent manner, the maximal contractile response induced by methoxamine (30 microm) in MAB. The endothelium-dependent relaxations were reversed by N(G)-nitro-L-arginine methyl ester (10 mM), whereas methylene blue (100 microM) was not capable of effectively inhibiting the AEIp-induced vasodilatation of MAB. The vasorelaxing effect of AEIp persisted in the presence of indomethacin (10 microM). These results suggest the involvement of NO of endothelial source (or others factors) in this vasodilatory effect.

Involvement of endothelium-derived NO in the basal tone and in the vasodilator responses to muscarinic agonists in the rat isolated mesenteric arterial bed.

To investigate the involvement of nitric oxide (NO) derived from endothelial cells in the control of vascular tone in the rat mesenteric vascular bed, the effects of different procedures known to interfere with the NO-cyclic GMP pathway were evaluated both on the basal tone and on the vasodilatory responses to four muscarinic agonists. To this aim, rat isolated mesenteric vascular beds were perfused at constant pressure. Water infusion significantly increased the resting perfusion pressure whereas L-NOARG, L-NAME and methylene blue were devoid of effect. In noradrenaline-preconstricted vascular bed, the perfusion pressure was significantly increased after water or L-NAME infusion. The vasodilator response induced by subsequent addition of acetylcholine in bolus was not significantly modified by pre-treatment with indomethacin but was significantly reduced by water infusion. Responses to acetylcholine and to three other muscarinic agonists--carbachol, oxotremorine or McNeil A 343--were assessed. Incubation with L-NAME did not modify the initial peak falls of the agonists except for McNeil A 343, whereas it significantly reduced the area under the pressure trace for all the substances. The latter effect was reversed after a subsequent incubation with L-Arginine. Finally, L-NAME strongly and significantly increased the drop in perfusion pressure and the area under the pressure trace following bolus of glyceryl trinitrate. These results suggest that in the mesenteric arterial bed of the rat, which can be considered as a resistant arteries preparation, basal tone appears to be controlled by a factor other than NO. Moreover, the vasodilator responses of muscarinic agonists are affected by L-NAME in their second late sustained phase only, which probably relies on a de novo synthesis of endothelium derived-NO. Finally, endothelium derived-NO exerts inhibitory effects both on the sensitivity of the vascular smooth muscle to glyceryl trinitrate and on the magnitude of its contraction in the presence of noradrenaline, two types of effects which are sensitive to L-NAME.

Basophil histamine release in patients with birch pollen hypersensitivity with and without allergic symptoms to fruits.

Histamine release (HR) studies were performed in 40 birch pollen-allergic patients (positive case history, positive SPT, positive birch pollen-specific serum IgE: RAST > or = 3) with (n = 20, A) and without (n = 20, B) fruit hypersensitivity, and 10 nonatopic volunteers (C). Several fruit allergens were used and characterized by protein determination and immunoblot techniques. Dose-dependent HR (apple peel = apple pulp > peach = cherry) was demonstrated in both allergic groups, but to a higher extent in patients with fruit allergy (P < 0.01). Increased basophil sensitivity to birch pollen was found in the group with fruit allergy (P < 0.001). Strong correlations between the mediator response induced by several fruits indicate common allergens within the extracts. We conclude that fruit-related symptoms require not only high specific serum IgE, but a strong cellular sensitization to birch pollen allergens together with an increased cellular reactivity to fruit allergens.

Effects of Piper sp extract on pregnancy in rats.

Abortive effects on cattle have been attributed to Piper sp, popularly called Pariparoba. In the present study we tested the possible toxicity of this plant by analyzing gestational outcome parameters in female rats given 300 mg/kg of an aqueous extract of Piper sp leaves and stalks per os, daily, between the 9th and the 21st day of pregnancy. The animals were killed just before delivery and the following features were observed: numbers of corpora albicantia, fetuses and reabsorptions; weights of fetuses, placentae and fetal membranes; fetal sex and the presence of overt malformations in fetuses; and implantation and reabsorption indices. No significant differences were detected between control and treated groups. The results suggest that Piper sp does not modify gestational outcome in rats.