RESUMO
The objective of the study was to examine the impact of a multi-strain probiotic (MSP) on sleep, physical activity, and body composition changes. We used a randomised, double-blind, placebo-controlled approach with 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented daily with MSP (4 × 109 live cells Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04; Probiotical S.p.A., Novara, Italy) or placebo (PLA). In response to supplementation (after 0, 2, 4, and 6 weeks of supplementation) and 3 weeks after stopping supplementation, participants had subjective (Pittsburgh Sleep Quality Index, PSQI) and objective sleep indicators, body composition, daily physical activity and resting hemodynamics assessed. Subjective sleep quality indicators using the PSQI (sleep latency, sleep disturbance, and global PSQI score) improved ( P < 0.05) at various time points with MSP supplementation. Systolic blood pressure in PLA increased ( P < 0.05) after 6 weeks of supplementation with no change in MSP. No changes ( P > 0.05) in sleep (hours asleep, minutes awake, number of times awake) or physical activity (step count, minutes of sedentary activity, total active minutes) metrics assessed by the wearable device were observed. Additionally, no changes in resting heart rate, diastolic blood pressure, and body composition were discerned. In conclusion, MSP supplementation improved the subjective ability to fall asleep faster and disturbances experienced during sleep, which resulted in improved overall sleep quality as assessed by the PSQI. No differences in other sleep indicators, physical activity, hemodynamics, and body composition were observed during or following MSP supplementation. Registered at clinicaltrials.gov: NCT05343533.
Assuntos
Composição Corporal , Exercício Físico , Hemodinâmica , Probióticos , Qualidade do Sono , Humanos , Probióticos/administração & dosagem , Masculino , Feminino , Método Duplo-Cego , Adulto , Exercício Físico/fisiologia , Hemodinâmica/efeitos dos fármacos , Adulto Jovem , Suplementos Nutricionais , Lacticaseibacillus rhamnosus/fisiologiaAssuntos
Doenças Genéticas Ligadas ao Cromossomo X/patologia , Microftalmia/patologia , Anormalidades da Pele/patologia , Deleção Cromossômica , Dermoscopia/métodos , Diagnóstico Diferencial , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Recém-Nascido , Microftalmia/diagnóstico , Microftalmia/genética , Pele/patologia , Anormalidades da Pele/diagnóstico , Anormalidades da Pele/genéticaRESUMO
We tested the hypothesis that liver protein kinase C (PKC) is increased in non-insulin-dependent diabetes mellitus (NIDDM). To this end we examined the distribution of PKC isozymes in liver biopsies from obese individuals with and without NIDDM and in lean controls. PKC isozymes alpha, beta, epsilon and zeta were detected by immunoblotting in both the cytosol and membrane fractions. Isozymes gamma and delta were not detected. There was a significant increase in immunodetectable PKC-alpha (twofold), -epsilon (threefold), and -zeta (twofold) in the membrane fraction isolated from obese subjects with NIDDM compared with the lean controls. In obese subjects without NIDDM, the amount of membrane PKC isozymes was not different from the other two groups. We next sought an animal model where this observation could be studied further. The Zucker diabetic fatty rat offered such a model system. Immunodetectable membrane PKC-alpha, -beta, -epsilon, and -zeta were significantly increased when compared with both the lean and obese controls. The increase in immunodetectable PKC protein correlated with a 40% elevation in the activity of PKC at the membrane. Normalization of circulating glucose in the rat model by either insulin or phlorizin treatment did not result in a reduction in membrane PKC isozyme protein or kinase activity. Further, phlorizin treatment did not improve insulin receptor autophosphorylation nor did the treatment lower liver diacylglycerol. We conclude that liver PKC is increased in NIDDM, a change that is not secondary to hyperglycemia. It is possible that PKC-mediated phosphorylation of some component in the insulin signaling cascade contributes to the insulin resistance observed in NIDDM.
Assuntos
Diabetes Mellitus Tipo 2/enzimologia , Isoenzimas/metabolismo , Fígado/enzimologia , Proteína Quinase C/metabolismo , Adulto , Animais , Diglicerídeos/metabolismo , Feminino , Humanos , Insulina/farmacologia , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/enzimologia , Florizina/farmacologia , Ratos , Receptor de Insulina/metabolismoRESUMO
The degradation of subendothelial and smooth muscle matrices by normal and neoplastic uroepithelial cells grown under serum-free conditions was examined. Normal urothelial cells were compared with neoplastic cells derived from a low grade papillary tumor (RT4) and a more invasive carcinoma (EJ). Low levels of degradation were observed with all cell types in serum-free medium alone. Supplementing the medium with plasminogen increased the degradative activity of each cell type. Logarithmically growing normal urothelial cells degraded extracellular matrix proteins 6 to 14 times faster on a per cell basis than their transformed counterparts. Analysis of the residual matrix constituents revealed that, while the levels of glycoprotein breakdown by the normal and neoplastic cells were similar, the normal cells degraded more of the collagen components than the neoplastic cells. Epidermal growth factor and cell density were examined as possible regulators of degradative activity. The neoplastic cells were not responsive to cell density as a regulatory factor and were only slightly responsive to epidermal growth factor. However, epidermal growth factor increased the degradative activity of logarithmically growing normal urothelial cells in the presence of plasminogen and the activity of confluent cells was increased to an even greater extent. Gelatin substrate gel analysis confirmed that the normal urothelial cells elaborated a more diverse set of gelatinases than the tumorigenic cells. Although normal urothelial cells had higher degradative abilities than their malignant counterparts, it is significant that the neoplastic cells were less responsive to regulatory signals in our model system. Thus, loss of regulatory mechanisms for protease secretion and matrix degradation may be a more important determinant of invasive ability in vivo than protease secretion or matrix degradation in vitro.
Assuntos
Matriz Extracelular/fisiologia , Peptídeo Hidrolases/metabolismo , Proteínas/metabolismo , Bexiga Urinária/fisiologia , Animais , Linhagem Celular , Células Cultivadas , Epitélio/fisiologia , Feto , Humanos , Cinética , Ratos , Células Tumorais Cultivadas/metabolismo , Neoplasias da Bexiga UrináriaRESUMO
The central nervous system (CNS) activities of a number of soterenol analogs have been investigated, and several of these compounds possessed potent morphine antagonistic and anorexiant properties. The CNS activity of these compounds was enhanced by certain lipophilic [e.g., 1,1-dimethyl-2-phenethyl (43) or cyclopropyl (40 and 44)] nitrogen substituents; however, minor structural changes on either the aromatic or side-chain moieties drastically reduced central activity. Toxicity in this series was related to the inherent alpha-adrenergic stimulating component (direct or indirect).
Assuntos
Agonistas Adrenérgicos beta/síntese química , Compostos de Anilina/síntese química , Sistema Nervoso Central/efeitos dos fármacos , Sulfonamidas/síntese química , Analgésicos , Compostos de Anilina/farmacologia , Compostos de Anilina/toxicidade , Animais , Etanolaminas/análogos & derivados , Cobaias , Técnicas In Vitro , Dose Letal Mediana , Masculino , Morfina/antagonistas & inibidores , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Quinonas/antagonistas & inibidores , Ratos , Tempo de Reação/efeitos dos fármacos , Reserpina/antagonistas & inibidores , Glândulas Seminais/efeitos dos fármacos , Relação Estrutura-Atividade , Sulfonamidas/farmacologia , Sulfonamidas/toxicidade , Traqueia/efeitos dos fármacosRESUMO
BACKGROUND: Previous studies have shown that ophthalmologists using blue-green argon laser may suffer subtle defects in their colour vision. A reduction in colour contrast sensitivity in the tritan colour confusion axis, an early manifestation of blue cone photoreceptor injury by the high energy photons of the laser, has been demonstrated and has prompted a reappraisal of laser safety in ophthalmology. Argon laser is also frequently used in scientific research, often at higher power output and for longer periods than is used in clinical practice. The scientists operating these lasers are at risk of developing similar phototoxic retinal injury. METHODS: The colour contrast sensitivity of 18 scientists who regularly use short wavelength argon laser was investigated. RESULTS: Eye protection was infrequently used and individuals had been subjected to between 580 and 7200 hours of cumulative laser exposure during the course of their research. CONCLUSION: The use of blue-green argon laser by the scientists investigated was not associated with a significant reduction in colour contrast sensitivity.
Assuntos
Percepção de Cores/efeitos da radiação , Defeitos da Visão Cromática/etiologia , Sensibilidades de Contraste/efeitos da radiação , Lasers/efeitos adversos , Doenças Profissionais/etiologia , Adulto , Argônio , Percepção de Cores/fisiologia , Sensibilidades de Contraste/fisiologia , Humanos , Pessoa de Meia-Idade , Ciência , Limiar Sensorial/fisiologia , Limiar Sensorial/efeitos da radiação , Fatores de TempoRESUMO
AIM: To correlate the phenotype of X linked congenital stationary night blindness (CSNBX) with genotype. METHODS: 11 CSNB families were diagnosed with the X linked form of the disease by clinical evaluation and mutation detection in either the NYX or CACNA1F gene. Phenotype of the CSNBX patients was defined by clinical examination, psychophysical, and standardised electrophysiological testing. RESULTS: Comprehensive mutation screening identified NYX gene mutations in eight families and CACNA1F gene mutations in three families. Electrophysiological and psychophysical evidence of a functioning but impaired rod system was present in subjects from each genotype group, although the responses tended to be more severely affected in subjects with NYX gene mutations. Scotopic oscillatory potentials were absent in all subjects with NYX gene mutations while subnormal OFF responses were specific to subjects with CACNA1F gene mutations. CONCLUSIONS: NYX gene mutations were a more frequent cause of CSNBX than CACNA1F gene mutations in the 11 British families studied. As evidence of a functioning rod system was identified in the majority of subjects tested, the clinical phenotypes "complete" and "incomplete" do not correlate with genotype. Instead, electrophysiological indicators of inner retinal function, specifically the characteristics of scotopic oscillatory potentials, 30 Hz flicker and the OFF response, may prove more discriminatory.
Assuntos
Canais de Cálcio Tipo L , Canais de Cálcio/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Cegueira Noturna/genética , Proteoglicanas/genética , Sequência de Bases , Testes de Percepção de Cores , Adaptação à Escuridão , Eletrorretinografia , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Genótipo , Humanos , Masculino , Dados de Sequência Molecular , Mutação , Cegueira Noturna/fisiopatologia , Fenótipo , Estudos Prospectivos , Retina/fisiopatologia , Transtornos da Visão/fisiopatologia , Acuidade Visual , Testes de Campo VisualAssuntos
Atenção à Saúde , Programas de Rastreamento/organização & administração , Oftalmologia/organização & administração , Retinopatia da Prematuridade/diagnóstico , Atenção à Saúde/organização & administração , Atenção à Saúde/normas , Inglaterra , Humanos , Recém-Nascido , Oftalmologia/normas , Telemedicina/organização & administração , Telemedicina/normasRESUMO
PURPOSE: To assess the tolerability and outcomes of laser treatment for retinopathy of prematurity (ROP) under sub-tenon anaesthetic with oral or rectal sedation using a reliable, multidimensional, and internationally accepted tool for assessment of neonatal pain. METHODS: Sixty-two babies have had ROP laser treatment in our neonatal unit in the 7-year interval between 1 March 2005 and 28 February 2012; 44% (27 of the 62) were performed using sub-tenon anaesthesia. Pain scores were routinely assessed using the Neonatal Pain Agitation and Sedation Scale (N-PASS) every 10 min during laser treatment. The outcome and requirement for re-treatment in this group was compared with that in the intravenous sedation group. RESULTS: Pain scores were available in 19 of the 27 babies treated under sub-tenon anaesthesia. The mean pain score during treatment was 2.7 (SD ± 1.7, range 0.5-6.2). There was no statistically significant correlation between the mean pain score and duration of treatment (Spearman correlation coefficient (ρ) = 0.31; P = 0.09), number of laser burns (ρ = 0.32; P = 0.09), or post-menstrual age of the baby at the time of treatment (ρ = 0.38; P = 0.052). Treatments performed under sub-tenon anaesthesia were as successful as those performed under intravenous sedation. The mean pain scores during laser treatment under sub-tenon anaesthesia in our study were lower than those previously reported during ROP screening or heel-stick procedure.Conclusion Our study demonstrated that sub-tenon anaesthesia with oral or rectal sedation provides sufficient pain control for laser treatment for ROP without the need or risks of intravenous sedation and intubation.
Assuntos
Anestesia Local/métodos , Dor Ocular/etiologia , Fotocoagulação a Laser , Medição da Dor , Retinopatia da Prematuridade/cirurgia , Acetaminofen/administração & dosagem , Analgésicos não Narcóticos/administração & dosagem , Anestésicos Locais/administração & dosagem , Peso ao Nascer , Hidrato de Cloral/administração & dosagem , Sedação Consciente/métodos , Idade Gestacional , Humanos , Hipnóticos e Sedativos/administração & dosagem , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Cápsula de Tenon , Resultado do TratamentoAssuntos
Aciltransferases/efeitos dos fármacos , Aciltransferases/metabolismo , Oxirredutases do Álcool/efeitos dos fármacos , Oxirredutases do Álcool/metabolismo , Intestinos/enzimologia , Retinoides/farmacologia , Vitamina A/farmacocinética , Animais , Anticarcinógenos/farmacologia , Fenretinida/farmacologia , Absorção Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Proteínas de Ligação ao Retinol/metabolismo , Vitamina A/sangue , Vitamina A/metabolismoRESUMO
BACKGROUND/AIMS: Fabry disease is an X linked lysosomal disorder associated with severe multiorgan failure and premature death. This study aims to determine the prevalence of ophthalmic manifestations in children with the condition and investigate the correlation with genotype and systemic disease severity. METHODS: The records of 26 children from 18 pedigrees with Fabry disease undergoing regular ophthalmic and systemic examination were reviewed. All pedigrees underwent GLA gene sequencing to determine genotype. Correlations between ocular and systemic phenotype and genotype were investigated. RESULTS: Corneal verticillata occurred in 50% of the children in this study (95% CI, 29% to 79%). Children with ophthalmic manifestations were more likely to have loss-of-function GLA mutations (p=0.003). Retinal vascular tortuosity was seen in seven children (27%), all of whom had systemic symptoms suggestive of autonomic neuropathy, such as diarrhoea and syncope. These symptoms seemed less prevalent in children without retinal vascular changes, although this did not reach statistical significance (p=0.134). CONCLUSION: Ophthalmic manifestations of Fabry disease are common even in young children with loss-of-function GLA gene mutations. Although the limited sample size possibly prevented statistical significance, systemic symptoms of autonomic neuropathy often coexist with retinal vascular changes and may share the same pathogenesis.
Assuntos
Anormalidades do Olho/diagnóstico , Oftalmopatias/diagnóstico , Doença de Fabry/diagnóstico , Doença de Fabry/epidemiologia , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Terapia de Reposição de Enzimas/métodos , Anormalidades do Olho/genética , Anormalidades do Olho/terapia , Oftalmopatias/epidemiologia , Oftalmopatias/genética , Oftalmopatias/terapia , Doença de Fabry/genética , Doença de Fabry/terapia , Feminino , Genótipo , Humanos , Masculino , Mutação , Linhagem , Fenótipo , Prevalência , Tamanho da Amostra , Índice de Gravidade de Doença , alfa-Galactosidase/uso terapêuticoAssuntos
Córtex Cerebral/metabolismo , Fenoxibenzamina/farmacologia , Piperazinas/farmacologia , Receptores de Serotonina/metabolismo , Trazodona/farmacologia , Animais , Córtex Cerebral/efeitos dos fármacos , Cinética , Masculino , Ratos , Receptores de Serotonina/efeitos dos fármacos , Espiperona/metabolismoAssuntos
Piperazinas/síntese química , Compostos de Espiro/síntese química , Tranquilizantes/síntese química , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Compostos Aza/síntese química , Compostos Aza/farmacologia , Compostos Aza/toxicidade , Comportamento Animal/efeitos dos fármacos , Sinergismo Farmacológico , Reação de Fuga/efeitos dos fármacos , Hexobarbital/farmacologia , Cetonas/síntese química , Cetonas/farmacologia , Cetonas/toxicidade , Camundongos , Atividade Motora/efeitos dos fármacos , Piperazinas/farmacologia , Piperazinas/toxicidade , Ratos , Compostos de Espiro/farmacologia , Compostos de Espiro/toxicidade , Tranquilizantes/farmacologia , Tranquilizantes/toxicidadeAssuntos
Condicionamento Operante/efeitos dos fármacos , Antagonismo de Drogas , Etanol/antagonistas & inibidores , Antagonistas dos Receptores Histamínicos H1/farmacologia , Anfetamina/farmacologia , Animais , Cafeína/farmacologia , Ciproeptadina/farmacologia , Imipramina/farmacologia , Masculino , Metilfenidato/farmacologia , Metiltirosinas/farmacologia , Pentilenotetrazol/farmacologia , Piperidinas/farmacologia , Piridinas/farmacologia , RatosRESUMO
PURPOSE: To determine whether patients with congenital stationary night blindness (CSNB) have electrophysiological evidence of optic nerve fibre mis-routing similar to that found in patients with ocular albinism (OA). METHOD: We recorded the Pattern Onset VEP using a protocol optimised to detect mis-routing of optic nerve fibres in older children and adults. We tested 20 patients (age 15-69 yrs) with X-linked or autosomal recessive CSNB, 14 patients (age 9-56 yrs) with OA and 13 normally pigmented volunteers (age 21-66 yrs). We measured the amplitude and latency of the CI component at the occipital midline and over left and right occipital hemispheres. We also assessed the computed inter-hemispheric "difference" signal. Subjects with CSNB were classified as having the "complete" or "incomplete" phenotype on the basis of their ERG characteristics. Members of X-linked CSNB pedigrees underwent mutation screening of the NYX and CACNA1F genes. RESULTS: CI was significantly smaller over the ipsilateral hemisphere and more prominent over the contralateral hemisphere in OA patients compared with both controls and CSNB patients. In CSNB patients CI response amplitudes were not significantly different from controls but peak latency was prolonged at all three electrodes compared with controls. The inter-hemispheric "difference" signal was abnormal for the OA group but not for the CSNB group. Contralateral dominance of CI could be identified in the majority of OA patients and the "difference" signal was opposite in polarity for left compared with right eye stimulation in every patient in this group. Only 3 of 20 patients with CSNB showed significant inter-hemispheric asymmetry similar to that seen in the OA patients. All 3 CSNB patients with evidence for optic nerve fibre mis-routing had X-linked pedigrees: 2 had an identified mutation in the NYX gene but no mutation in either the NYX or CACNA1F genes was identified in the third. VEP evidence of optic nerve fibre mis-routing was present in 3 of the 11 subjects with "complete" phenotype and none of the 9 patients with "incomplete" phenotype CSNB. CONCLUSION: Mis-routing of optic nerve fibres does occur in CSNB but we found evidence of it in only 15% of our patients.
Assuntos
Potenciais Evocados Visuais , Fibras Nervosas/fisiologia , Cegueira Noturna/congênito , Cegueira Noturna/diagnóstico , Nervo Óptico/fisiopatologia , Adolescente , Adulto , Idoso , Criança , Genótipo , Humanos , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Basic fibroblast growth factor (bFGF) is a multifunctional growth factor that can stimulate cell proliferation, production of proteases, and angiogenesis. Loss of mechanisms that regulate bFGF activity could result in tumor development. To test this idea, cells derived from an invasive bladder carcinoma (EJ) were compared with cells derived from a noninvasive bladder carcinoma (RT4) for the expression of bFGF and high and low affinity FGF receptors. bFGF was produced by the invasive EJ cells but not by the noninvasive RT4 cells, suggesting that bFGF could act in an autocrine fashion in the EJ cells to promote their invasion and growth in the surrounding tissue. The two cells lines also showed differences in FGF receptor expression. The EJ cells expressed both high and low affinity FGF receptors as determined by Scatchard analysis, whereas the RT4 cells expressed only high affinity receptors. The high affinity receptors on the RT4 cells were not recognized by an antibody to known FGF receptors. Furthermore, in contrast to the EJ cells, bFGF did not induce protein tyrosine phosphorylation in the RT4 cells. Thus these data suggest that the invasive potential of bladder carcinoma cells may be regulated by the expression of both bFGF and its receptors.
Assuntos
Carcinoma/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Receptores de Superfície Celular/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Ligação Competitiva , Northern Blotting , Carcinoma/patologia , Humanos , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/patologiaRESUMO
In this study we compare the cosmetic and functional results of the common reconstructive techniques used in the management of patients with clitoral hypertrophy. We find impressive benefits in a surgical procedure that includes excision of the clitoral shaft with preservation of the glans and ventral mucosa combined with simple introitoplasty. We recommend reserving definitive vaginoplasty as needed until the age of puberty. Our experience is this clinical area is being offered with attention to the long-term followup of patients.