Full-spectrum cannabidiol reduces UVB damage through the inhibition of TGF-ß1 and the NLRP3 inflammasome.

The thermodynamic characteristics, antioxidant potential, and photoprotective benefits of full-spectrum cannabidiol (FS-CBD) against UVB-induced cellular death were examined in this study. In silico analysis of CBD showed antioxidant capacity via proton donation and UV absorption at 209.09, 254.73, and 276.95 nm, according to the HAT and SPLET methodologies. FS-CBD protected against UVB-induced bacterial death for 30 min. FS-CBD protected against UVB-induced cell death by 42% (1.5 µg/mL) and 35% (3.5 µg/mL) in an in vitro keratinocyte cell model. An in vivo acute irradiated CD-1et/et mouse model (UVB-irradiated for 5 min) presented very low photoprotection when FS-CBD was applied cutaneously, as determined by histological analyses. In vivo skin samples showed that FS-CBD regulated inflammatory responses by inhibiting the inflammatory markers TGF-ß1 and NLRP3. The docking analysis showed that the CBD molecule had a high affinity for TGF-ß1 and NLRP3, indicating that protection against inflammation might be mediated by blocking these proinflammatory molecules. This result was corroborated by the docking interactions between CBD and TGF-ß1 and NLRP3, which resulted in a high affinity and inhibition of both proteins The present work suggested a FS-CBD moderate photoprotective agent against UVB light-induced skin damage and that this effect is partially mediated by its anti-inflammatory activity.

Evaluation of different doses of mashua (Tropaeolum tuberosum) on the reduction of sperm production, motility and morphology in adult male rats.

Mashua is an edible-tuber crop that grows in the Andean region. Folk medicine describes the use of mashua to reduce reproductive function in men. The present study aimed: (i) to determine whether different doses of mashua (0.01, 0.1, 1 and 2 g kg(-1)) produced a dose-response reduction on sperm production and quality; and, (ii) to determine whether these anti-reproductive effects of mashua can be reversible after cessation of treatment (12 and 24 days of recovery time). Mashua-treated rats showed lower values of daily sperm production, epididymal and vas deferens sperm count and sperm motility; meanwhile, mashua increased the percentage of abnormal sperm morphology and epididymal sperm transit rate. The following variables follow a dose-response effect: sperm number in vas deferens, sperm motility and sperm transit rate. In addition, it was demonstrated that the reduction in reproduction function in male rats treated with mashua was reversible after 24 days of recovery time. Finally, lower doses mashua reduces sperm number and quality (motility and morphology), and these adverse effects on male reproductive system may be reversible after 24 days after cessation of the treatment.

Tropaeolum tuberosum (Mashua) reduces testicular function: effect of different treatment times.

Tropaeolum tuberosum Ruiz & Pavon, along with other several species, is an edible-tuber crop that grows in the Andean region. Folk medicine describes the use of mashua to reduce reproductive function in men. The present study aimed to evaluate the effect of mashua (1 g kg(-1)) on sperm production in rats during 7, 12, 21 and 42 days of treatment. The following parameters were assessed: reproductive organ weights, spermatid count and daily sperm production (DSP), sperm count in epididymis and sperm transit and serum testosterone levels. Freeze-dried extract of mashua had 3.7 g 100 g(-1) of benzyl glucosinolate. Mashua-treated rats showed a reduction in testicular spermatid number and DSP from day 12 to day 42; meanwhile, the effect of mashua was noted in epididymal sperm count after 12 and 42 days of treatment. In addition, epididymal sperm transit time was delayed at day 7 and it was accelerated on days 12 and 21 of treatment. No differences in serum testosterone levels were found between rats treated with vehicle and mashua after 42 days of treatment. Finally, mashua reduces testicular function after one spermatogenic cycle by reducing spermatid and sperm number, DSP and epididymal sperm transit time.

Enhancement of the nutritional status and quality of fresh pork sausages following the addition of linseed oil, fish oil and natural antioxidants.

Fresh pork sausages (pork shoulder, pork back fat, water, rusk and seasoning) were manufactured where 15% of the pork back fat was substituted with linseed oil (LO) or fish oil (FO). Green tea catechins (GTC) and green coffee antioxidant (GCA) were added to both LO (LGTC 200 and LGCA 200) and FO (FGTC 200 and FGCA 200) substituted sausages at a level of 200mg/kg. Raw and cooked pork sausages were either over-wrapped with oxygen permeable film (aerobic storage) or stored in modified atmosphere packages (MAP) containing 80% O(2):20% CO(2) or 70% N(2):30% CO(2), respectively for 7 days at 4°C. Effects on fatty acid profiles, lipid oxidation, colour and sensorial properties were investigated. α-Linolenic acid increased from 1.34% (control) to 8.91% (LO) and up to 11.2% (LGTC 200 and LGCA 200). Addition of fish oil increased levels of EPA from 0.05% (control) to 2.83% (FO), 3.02% (FGTC 200) and 2.87% (FGCA 200) and DHA levels increased from 0.04% (control) to a maximum of 1.93% (FGTC 200). Lipid oxidation was low in raw and cooked linseed oil containing sausages. GTC (200mg/kg) significantly (P<0.05) reduced lipid oxidation in raw fish oil containing sausages after 7 days of storage. Colour parameters in raw pork sausages were unaffected by the packaging atmosphere. L(∗) lightness values were lower (P<0.05) in LGTC 200 and a(∗) redness values lower (P<0.05) in LGTC 200 and FGTC 200 after 7 days of storage. Sensory scores of cooked pork sausages were unaffected by linseed oil addition. Flavour and overall acceptability scores in cooked fish oil containing sausages were improved by GTC addition. Results obtained demonstrate potential for the production of nutritionally enhanced fresh pork sausages.

Personality traits and temporomandibular disorders in a group of children with bruxing behaviour.

The aim of the present study was to compare the personality pattern, the anxiety level and the temporomandibular disorders (TMD) between bruxist and non-bruxist children with mixed dentition. Fifty-two subjects, with a mean age of 9.45 years (range 8-11) were evaluated and classified as bruxist (n = 26), according to the American Academy of Sleep Medicine (AASM) and the presence of dental wear clinically visible, under the same conditions of artificial light and position. The control children (n = 26) did not present dental wear and did not accomplished all the AASM criteria. The personality pattern and the anxiety of the bruxist children were studied by means of the Children's Personality Questionnaire (CPQ) and the Conners' Parents Rating Scales (CPRS), respectively, and compared with the personality traits and the anxiety level of a non-bruxist population. The TMD were also evaluated using the Research Diagnostic Criteria for temporomandibular disorders (RDC/TMD) criteria. The data were analysed with the student's t-test, Fisher's exact test and chi-squared tests. A multivariated analysis was performed using a logistic regression with the stepwise likelihood ratio method. Compared with the controls, the bruxist children had significantly higher tension personality and were more anxiety prone. The bruxist children presented more TMD-related signs and symptoms than children in the control group. A strong correlation was found among bruxism, TMD, the high anxiety level and the high tension personality trait.

Cortical hypoactivation during resting EEG suggests central nervous system pathology in patients with chronic fatigue syndrome.

We investigated central fatigue in 50 patients with chronic fatigue syndrome (CFS) and 50 matched healthy controls (HC). Resting state EEG was collected from 19 scalp locations during a 3 min, eyes-closed condition. Current densities were localized using exact low-resolution electromagnetic tomography (eLORETA). The Multidimensional Fatigue Inventory (MFI-20) and the Fatigue Severity Scale (FSS) were administered to all participants. Independent t-tests and linear regression analyses were used to evaluate group differences in current densities, followed by statistical non-parametric mapping (SnPM) correction procedures. Significant differences were found in the delta (1-3 Hz) and beta-2 (19-21 Hz) frequency bands. Delta sources were found predominately in the frontal lobe, while beta-2 sources were found in the medial and superior parietal lobe. Left-lateralized, frontal delta sources were associated with a clinical reduction in motivation. The implications of abnormal cortical sources in patients with CFS are discussed.

Nutritional and sensory properties of dry fermented sausages enriched with n-3 PUFAs.

Enrichment of dry fermented sausages with n-3 fatty acids through a partial substitution of pork backfat by deodorised fish oil resulted in improved nutritional properties with regard to conventional sausages, without affecting sensory properties and oxidation status. The developed products supplied 0.64g EPA/100g and 0.46g DHA/100g product, and showed PUFA+MUFA/SFA ratio of 1.76 and n-6/n-3 ratio of 2.97. No signs of oxidation were found in any type of sausages, control and modified. None of the dienals and trienals reported as secondary lipid oxidation products and typical for fish oil were detected in the modified sausages. Instrumental colour differences were detected, however, without relevance in the sensory analysis. The sensory evaluation panel did not find differences in general acceptability. The modified dry fermented sausages can be considered a technologically viable functional food.

Stability of linseed oil and antioxidants containing dry fermented sausages: A study of the lipid fraction during different storage conditions.

Different packaging conditions (aerobic, vacuum and modified atmosphere) were evaluated in order to study the stability of the lipid fraction of dry fermented sausages manufactured with a partial substitution of pork backfat by linseed oil and antioxidants. After 5 months of storage, α-linolenic acid was better preserved by vacuum and MAP (7.32 and 7.74g/100g fatty acids, respectively) than in aerobic conditions (6.15g/100g fatty acids), without significant differences to values obtained after 2 months of storage for this acid. At the end of the storage, (n-6)/(n-3) fraction in sausages with linseed oil was in all cases lower than 3, in contrast to values obtained for control products that were all higher than 15. Better PUFA/SFA ratios were also observed in modified sausages (0.6-0.7g/100g fatty acids) than control ones (0.3-0.4g/100g fatty acids). No signs of lipid oxidation measured by TBARs and peroxides were detected for modified sausages regardless the packaging system used (TBARs values lower than 0.25ppm and peroxides lower than 4meq O(2)/kg), pointing at a high effectiveness of the antioxidants. Furthermore, vacuum and MAP prevented 2,4-decadienal formation. Nutritional benefits of linseed oil and antioxidants containing products were maintained after 5 months of storage.

[Functional components in fish and algae oils]. / Componentes funcionales en aceites de pescado y de alga.

An important area of the development of new functional foods is facussed on finding or applying food components which favour achieving a healthier lipid profile in the organism. The objective of this work was to carry out the characterisation of the lipid fraction of two oils, fish oil and algae oil, to evaluate their potential use as functional ingredients, in relation to the high molecular weight fatty acid content and the presence of sterols and other components of the unsaponificable fraction. Both oils showed a lipid fraction rich in high molecular weight polyunsaturated omega-3 fatty acids, containing a 33.75% in the fish oil and a 43.97% in the algae oil. Eicosapentaenoic acid was the major fatty acid in fish oil, whereas docosahexaenoic was the most abundant fatty acid in algae oil. The omega-6/omega-3 ratio was lower than 0.4 in both oils. In the unsaponificable fraction, algae oil had a Mold lower cholesterol content and a higher proportion of squalene than fish oil. The phytosterol content was significantly higher in the algae oil.

The use of tissue-engineered skin (Apligraf) to treat a newborn with epidermolysis bullosa.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a mechanobullous disorder. The Dowling-Meara variant, a subtype of EB, is characterized by widespread blister formation that may include the oral cavity and nails. Many patients with the Dowling-Meara phenotype are at increased risk of sepsis and death during infancy. The treatment of EB is generally supportive. The tissue-engineered skin used (Apligraf) is a bilayered human skin equivalent developed from foreskin. It is the only Food and Drug Administration-approved skin equivalent of its kind. It is approved for the treatment of venous ulcers of the lower extremities. It has also been used to treat acute wounds, such as graft donor sites and cancer excision sites. OBSERVATION: To our knowledge, we describe the first case in which a newborn with EB, Dowling-Meara variant, was treated with bilayered tissue-engineered skin. The areas treated with the tissue-engineered skin healed faster than the areas treated with conventional therapy. Most of the areas treated with tissue-engineered skin have remained healed, without developing new blisters. These areas appear to be more resistant to trauma. CONCLUSIONS: Our early success with tissue-engineered skin in this patient may have a significant impact on the future treatment of neonates with EB simplex. Future studies are needed to determine if the beneficial effects of tissue-engineered skin are reproducible in other neonates with EB simplex and in patients of all ages with different subtypes of EB.

Tissue-engineered skin (Apligraf) in the healing of patients with epidermolysis bullosa wounds.

BACKGROUND: At present, wound treatment of inherited epidermolysis bullosa (EB) is only supportive. OBJECTIVE: To determine the safety and clinical effects of tissue-engineered skin (Apligraf; Organogenesis Inc, Canton, Mass) in the healing of wounds of patients with different types of EB. DESIGN: An open-label uncontrolled study of 15 patients with EB treated with tissue-engineered skin. Each patient received tissue-engineered skin on up to 2 wounds on each of 3 clinic visits: day 1, week 6, and week 12. They were evaluated 7 (+/- 3) days and 6 weeks after each round of treatment. A quality-of-life survey was administered during week 6. SETTING: University of Miami, Miami, Fla. PATIENTS: Volunteers with EB. MAIN OUTCOME MEASURE: Safety and wound healing. RESULTS: A total of 69 different acute wounds received tissue-engineered skin at the day-1 (24 wounds), week-6 (23 wounds), and week-12 (22 wounds) visits. Overall, 63 wounds (79%) were found healed at the day-7 visit. Of the acute wounds, 82% (51/62) were healed 6 weeks after being treated, 75% (27/36) after 12 weeks, and 79% (11/14) after 18 weeks. Nine chronic wounds were also treated. Four were healed at 6 weeks; however, 7 were still open at the last clinic visit (week 18). There were no signs of rejection or clinical infection and no adverse events related to the tissue-engineered skin. The quality of life for most patients improved after treatment. Compared with patients' recollection of wounds treated with standard dressings, healing was faster and less painful. CONCLUSION: In this series of patients, tissue-engineered skin induced very rapid healing, was not clinically rejected, and was devoid of adverse effects. It was felt by the patients and families to be more effective than conventional dressings for EB wounds.

Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy.

OBJECTIVE: To characterize the epidemiological, clinical, and histopathological features of patients with cancer who develop widespread polymorphic and pruritic skin lesions following radiotherapy. PATIENTS, DESIGN, AND INTERVENTIONS: During phase 1, epidemiological and clinical features of 103 patients with cancer, 83 treated with radiotherapy (71 women and 12 men) and 20 controls who did not undergo radiotherapy (16 women and 4 men), were explored during 3 months (October 1995 to January 1996). During phase 2, in 30 additional patients with cancer who were treated with telecobalt or linear accelerator, 18 with skin lesions (15 women and 3 men) and 12 without lesions (10 women and 2 men), the following were investigated: (1) hematoxylin-eosin-stained sections for routine histopathological examination and direct immunofluorescence, and lymphocytic markers; (2) blood, skin, and primary tumor eosinophilia; and (3) the presence of antiepidermal autoantibodies. Patients were examined during 5 months (February 1996 to June 1996). SETTING: A dermatology department at a university hospital. RESULTS: During phase 1, 14 (17%) of the 83 patients undergoing radiotherapy developed an eruption. Acral excoriations, erythematous papules, vesicles, and bullae were the most frequent lesions. During phase 2, in 18 patients, a superficial and deep lymphocytic perivascular infiltrate with numerous eosinophils, intraepidermal and interstitial eosinophilic infiltrates, eosinophilic panniculitis, IgM and C3 perivascular deposits, and slightly predominant CD4+ cells were observed. No antiepidermal autoantibodies were found. CONCLUSIONS: The clinical, histopathological, and immunopathologic features in patients with cancer undergoing radiotherapy are described. To our knowledge, this condition has not been well characterized. Because of its unique presentation, the denomination "eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy" is suggested.

alpha-Methylnoradrenaline-induced contractions in rat aorta are mediated via alpha 1D-adrenoceptors.

The subtype(t) of alpha-adrenoceptor-mediating contractions to alpha-methynoradrenaline in the rat aorta has been investigated by using alpha-adrenoceptor-selective competitive antagonists and the alpha 1-adrenoceptor selective agonist, phenylephrine, for comparison. alpha-Methylnoradrenaline and phenylephrine elicited concentration-dependent contractions in the endothelium-denuded and endothelium-intact aortic rings with similar potencies and maximal effects. alpha-Methylnoradrenaline- and phenylephrine-induced contractions in endothelium-denuded aortic rings were competitively antagonized by prazosin (pA2 = 9.38 and 9.13; respectively) and rauwolscine (pA2 = 7.19 and 6.60, respectively). This confirms that there is an alpha 1- and a non alpha 2-adrenoceptor response to alpha-methylnoradrenaline in the rat aorta. The subtype selective alpha 1D-adrenoceptor antagonist, BMY 7378, was found to antagonize contractions to alpha-methylnoradrenaline and phenylephrine competitively in endothelium-denuded and endothelium-intact aortic rings. The pA2 values of BMY 7378 against alpha-methylnoradrenaline (8.39 and 8.41; endothelium-intact and endothelium-denuded, respectively) and phenylephrine (8.64 and 8.76; endothelium-intact and endothelium-denuded, respectively), are consistent with its published functional potency and clonal alpha 1D-adrenoceptor binding affinity. In addition, contractions to alpha-methylnoradrenaline and phenylephrine in endothelium-denuded aortic rings, were potently inhibited by WB 4101 with pA2 values of 9.75 and 9.25, respectively. The high pA2 values for WB 4101 indicate that the alpha 1B-adrenoceptor subtype does not seem to participate in alpha-methylnoradrenaline (and phenylephrine) induced contractions in this artery. These results suggest that the alpha 1D-subtype plays a determining role in rat aorta contractions induced by alpha-methylnoradrenaline.

Effects of thiopental on endothelium-dependent responses in rat aorta.

Effects of pretreatment with thiopental on endothelium-dependent vasodilator responses elicited by drugs in rat aortic rings were investigated. The vasodilators employed were acetylcholine and histamine (endothelium- and receptor-dependent), A23187 (endothelium-dependent but receptor-independent) and sodium nitroprusside (endothelium-independent); they were tested 15 or 60 min after aortic preparations were exposed during 15 min to thiopental. Pretreatment with the barbiturate reversibly inhibited relaxation elicited by either acetylcholine and histamine, but a high concentration of the anesthetic was needed (3.1 mg/ml). On the contrary, thiopental did not modify the relaxation elicited by sodium nitroprusside or A23187. In addition, the barbiturate inhibited basal and acetylcholine-stimulated production of nitrites (an indicator of nitric oxide output) in aortic rings. In conclusion, thiopental inhibited the endothelium-dependent relaxation elicited by either acetylcholine or histamine. Although the barbiturate also inhibited nitric oxide production, the reduction in the relaxant response provoked by it does not seem to be the result of direct guanylate cyclase or nitric oxide synthase alterations, since thiopental did not modify the effect of sodium nitroprusside or A23187. Disturbances elicited by thiopental on endothelial receptors or on signal transduction elements may indirectly provoke nitric oxide synthase inhibition.

Vagus nerve stimulation in pediatric epilepsy: a review.

Therapeutic options for intractable epilepsy include new and investigational antiepileptic drugs, ketogenic diet, epilepsy surgery, and, now, vagus nerve stimulation, which is approved by the U.S. Food and Drug Administration for the treatment of refractory partial seizures in adolescents and adults. The exact mechanisms of action are unknown. Although the use of vagus nerve stimulation in children has increased, including those younger than 12 years of age or those with generalized epilepsy, there has been no large controlled pediatric study to date. The identification of favorable prognostic indicators, especially in children, would be useful. Preliminary results suggest that children with Lennox-Gastaut syndrome may have a favorable response, with improvement in both seizure control and global evaluation scores. Improved global evaluation scores have occurred even without an associated improvement in seizure control.

Skin grafting.

No longer an option of last resort, skin grafting has become a technique that is routinely and sometimes preferentially considered as skin replacement for burns, chronic ulcers, and skin defects after cutaneous surgical procedures. When selected as the best alternative for wound closure, autologous skin grafts are commonly considered the gold standard. Availability of autologous grafts is a major obstacle, however, and the search for a manufactured skin replacement has continued. In cases in which autologous grafts cannot be performed, skin substitutes have become an attractive alternative.

Auditory evoked response data reduction by PCA: development of variables sensitive to reading disability.

Long latency auditory evoked responses (AER) were formed on 232 healthy normal and learning impaired subjects to tone pairs of 50 msec inter-stimulus interval (TALAER) and also to the words "tight" and "tyke" (TTAER). Both evoked potential (EP) type have been used to demonstrate differences between good readers (WIAT Basic Reading score > 115, N = 42) and poor readers (Reading score < 85, N = 42). A largely automated, hands off approach was used to reduce artifact contamination, to develop canonical measures for discriminating good from poor readers, and to predict reading scores across the entire population including intermediate (average) readers. Eye and muscle artifact were diminished by multiple regression. Substantial EP data reduction was enabled by an unrestricted use of Principal Components Analysis (PCA). For each EP type, 40 factors encompassed 70-80% of initial variance, a meaningful data reduction of about 90:1. Factor interpretation was enhanced by mapping of the factor loadings. By discriminant analysis, resulting factors predicted reading group membership with over 80% jackknifed and also split--half replication accuracy. By multiple regression, they produced a canonical variate correlating significantly (p < 0.001) with the Basic Reading score (r = 0.39). The TTAER factors were more useful than the TALAER factors. The relevance of rapid auditory processing and phonemic discrimination measurements to dyslexia is discussed.

Auditory evoked responses to similar words with phonemic difference: comparison between children with good and poor reading scores.

Our previous study demonstrated a physiologic deficit in two-tone discrimination in poor readers. This was specific to the left parietal area suggesting that poor readers handled rapid tones differently. The current paper extends this finding in the same population, demonstrating that poor readers also have difficulty with phonemic discrimination. Long latency auditory evoked potentials (AEP) were formed using a phonemic discrimination task in a group of children with reading disabilities and controls. Measuring peak-to-peak amplitude of the waveforms, we found reduced N1-P2 amplitude in the Poor Reader group. Using the t-statistic significance probability map (SPM) technique, we also found a group difference, maximal over the mid-parietal area, from 584 msec to 626 msec after the stimulus onset. This difference was due to a lower amplitude on the Poor Reader group. We hypothesized that this late difference constitutes a P3 response and that the Poor Reader group generated smaller P3 waves. These auditory evoked response (AER) data support a discrimination deficit for close phonemes in the Poor Reader group as they had smaller N1-P2 absolute amplitude and developed smaller P3 waves. Based on these data we should be able to differentiate between Good and Poor readers based on long latency potentials created from phonemic stimuli.

[Fetal neurological evaluation]. / Evaluación neurológica del feto.

AIM: To review recent advances in the procedures and techniques that have made possible to evaluate the anatomy and function of the central nervous system (CNS) in the fetus. DEVELOPMENT: The neurological evaluation of the fetus can be performed at different levels: clinical, anatomical and functional. At a clinical level the analysis of body, ocular or respiratory fetal movements, as well as fetal heart rate, defines 4 behavioural states: 1F and 2F correspond to the quiet and active sleep, respectively. States 3F and 4F occur during wakefulness in the newborn, but there is no scientific evidence that the fetus is awake. Behavioral states probably play an important role in the process of CNS maturation and development. Anatomic evaluation of the CNS to rule out brain malformations can be performed with ultrasound since week 7-8 of gestational age and with magnetic resonance imaging (MRI) since week 18-20. Both techniques are also useful in the diagnosis of acquired fetal neurological diseases. Both modalities are concordant in the majority of cases, but in others each of them provides additional, different information. Computed tomography should only be used in selected cases that involve bone structures. Functional evaluation of fetal CNS can be performed with proton MR spectroscopy, which determines the cerebral content of inositol, choline, creatine and N-acetylaspartate. Other techniques to functionally study the fetal brain are functional MRI (fMRI), near infrared spectroscopy, and magnetoencephalography. CONCLUSIONS: Fetal neurology is a discipline that will continue to develop fast in the immediate future. Technological advances will facilitate the possibility of a more rapid and reliable diagnosis of anatomic or functional abnormalities of the fetal CNS.