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1.
Proc Natl Acad Sci U S A ; 111(35): 12930-5, 2014 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-25136096

RESUMO

Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the gene encoding for the anion channel cystic fibrosis transmembrane conductance regulator (CFTR). Several organs are affected in CF, but most of the morbidity and mortality comes from lung disease. Recent data show that the initial consequence of CFTR mutation is the failure to eradicate bacteria before the development of inflammation and airway remodeling. Bacterial clearance depends on a layer of airway surface liquid (ASL) consisting of both a mucus layer that traps, kills, and inactivates bacteria and a periciliary liquid layer that keeps the mucus at an optimum distance from the underlying epithelia, to maximize ciliary motility and clearance of bacteria. The airways in CF patients and animal models of CF demonstrate abnormal ASL secretion and reduced antimicrobial properties. Thus, it has been proposed that abnormal ASL secretion in response to bacteria may facilitate the development of the infection and inflammation that characterize CF airway disease. Whether the inhalation of bacteria triggers ASL secretion, and the role of CFTR, have never been tested, however. We developed a synchrotron-based imaging technique to visualize the ASL layer and measure the effect of bacteria on ASL secretion. We show that the introduction of Pseudomonas aeruginosa and other bacteria into the lumen of intact isolated swine tracheas triggers CFTR-dependent ASL secretion by the submucosal glands. This response requires expression of the bacterial protein flagellin. In patients with CF, the inhalation of bacteria would fail to trigger ASL secretion, leading to infection and inflammation.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrose Cística/microbiologia , Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa/metabolismo , Traqueia/metabolismo , Traqueia/microbiologia , Animais , Fibrose Cística/imunologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/imunologia , Feminino , Haemophilus influenzae/metabolismo , Imunidade Inata/fisiologia , Masculino , Mucinas/metabolismo , Infecções por Pseudomonas/imunologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/microbiologia , Staphylococcus aureus/metabolismo , Suínos , Síncrotrons , Traqueia/imunologia
2.
Muscle Nerve ; 49(1): 84-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23588824

RESUMO

INTRODUCTION: In this study we investigated the clinical utility of single fiber conduction velocity (SF-CV) testing in the evaluation of motor nerve function in diabetic patients with signs and symptoms of symmetrical distal sensory polyneuropathy (DSP). SF-CV findings were compared with conventional nerve conduction studies (NCS). METHODS: Twenty-eight consecutive type 2 diabetic patients with clinically diagnosed DSP were studied. RESULTS: SF-CV testing of the tibial nerve was abnormal in 16 (57.1%) patients. Twelve patients with normal conventional motor NCS had abnormal findings by tibial SF-CV. SF-CV testing of the tibial nerve was significantly superior to all other motor NCS. CONCLUSIONS: SF-CV testing of the tibial nerve often demonstrates motor nerve impairment in diabetic patients with sensory DSP when conventional NCS are normal.


Assuntos
Nefropatias Diabéticas/fisiopatologia , Neurônios Motores/fisiologia , Fibras Nervosas/fisiologia , Condução Nervosa/fisiologia , Adulto , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Eletrofisiologia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Tibial/fisiopatologia , Nervo Ulnar/fisiopatologia
3.
J Affect Disord ; 355: 422-425, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38537756

RESUMO

BACKGROUND: Patients with major depression often suffer from excessive interpersonal sensitivity, although it is not typically measured in antidepressant clinical trials. Preliminary evidence suggests selective serotonin reuptake inhibitors have the capacity to reduce interpersonal sensitivity. METHODS: This was a pooled analysis of data from 1709 patients in three randomized, double-blind, placebo-controlled trials of fluoxetine and paroxetine for acute major depressive disorder. Depressive symptoms were assessed with the Hamilton Depression Rating Scale. A factor from the Symptom Checklist was used to assess interpersonal sensitivity. Our outcome of interest was change from baseline scores at the last assessment (up to 8 or 12 weeks, depending on the trial). RESULTS: Both medications produced significantly greater reductions in interpersonal sensitivity relative to placebo. The effect of medication remained significant after controlling for depression improvement, which explained 18.5% of the variation in interpersonal sensitivity improvement among those treated with active medication. The effect of medication on depressive symptoms, relative to placebo, was not influenced by baseline interpersonal sensitivity. LIMITATIONS: The outcome measured interpersonal sensitivity over the last week, and the results do not necessarily reflect changes in long-standing, trait-like patterns of interpersonal sensitivity. Only two medications were studied. CONCLUSIONS: Selective serotonin reuptake inhibitors are effective at treating interpersonal sensitivity in acutely depressed patients. This appears to be a unique drug effect that is not only the result of depression improvement. Future clinical trials might benefit from assessing interpersonal sensitivity more routinely.


Assuntos
Transtorno Depressivo Maior , Inibidores Seletivos de Recaptação de Serotonina , Humanos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Depressão , Antidepressivos/uso terapêutico , Paroxetina/uso terapêutico , Fluoxetina/uso terapêutico , Método Duplo-Cego , Resultado do Tratamento
4.
Trop Anim Health Prod ; 45(2): 411-6, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22820941

RESUMO

The objective of this study was to determine the effect of timing of artificial insemination on pregnancy rates, calving rates, abortion rates, twinning rates, and calf gender ratio after synchronization of ovulation with Ovsynch protocol in Holstein dairy cows. The ovulation of 219 lactating Holstein dairy cows was synchronized using the Ovsynch protocol. Therefore, cows received an injection of GnRH followed by an injection of prostaglandin F(2α) 7 days later and a second treatment with GnRH 2 days later. Cows were artificially inseminated at 0, 12, or 24 h after the second injection of GnRH. Reproductive performance did not differ between cows inseminated at 0 h (n = 82), 12 h (n = 66), or 24 h (n = 71) after the last injection of GnRH (pregnancy rate: 0 h 48 %, 12 h 47 %, 24 h 52 %; abortion rate: 0 h 5 %, 12 h 0 %, 24 h 11 %; calving rate: 0 h 43 %, 12 h 47 %, 24 h 41 %; twinning rate: 0 h 2 %, 12 h 0 %, 24 h 0 %; calf gender ratio (F/M): 0 h 61:39 %, 12 h 48:52 %, 24 h 39:61 %; P > 0.05). Pregnancy rates for cows inseminated in postpartum times of 50-75, 76-100, and >100 days within the first and ≥ 3 parities were statistically similar (P > 0.05), but pregnancy rates for cows inseminated at different postpartum times of 50-75, 76-100, and >100 days within the second parity were different (P < 0.01). In general, pregnancy rates of cows inseminated at different postpartum times (P < 0.01) and parities (P < 0.001) differed. The findings of the current study showed that rates of pregnancy, abortion, calving, and twinning of Holstein dairy cows subjected to artificial insemination at different times after synchronization were similar. These results also indicate that the timing of artificial insemination after synchronization did not influence calf gender ratio. Furthermore, pregnancy rates of Holstein dairy cows inseminated after synchronization were significantly influenced by postpartum time and parity number.


Assuntos
Bovinos/fisiologia , Indústria de Laticínios/métodos , Inseminação Artificial/veterinária , Ovulação/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Aborto Animal/epidemiologia , Aborto Animal/etiologia , Animais , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/etiologia , Distribuição de Qui-Quadrado , Dinoprosta/administração & dosagem , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Lactação , Modelos Logísticos , Indução da Ovulação/veterinária , Gravidez , Taxa de Gravidez , Razão de Masculinidade , Fatores de Tempo , Turquia/epidemiologia
5.
Animals (Basel) ; 13(14)2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37508143

RESUMO

This study was carried out in order to determine the morphological characteristics, body coat colour distribution, and body dimensions of donkeys raised in Turkey, as well as to determine the relationships between these factors. For this reason, the predictive performance of various machine learning algorithms (i.e., CHAID, Random Forest, ALM, MARS, and Bagging MARS) were compared, utilising the biometric data of donkeys. In particular, mean measurements were taken from a total of 371 donkeys (252 male and 119 female) with descriptive statistical values as follows: height at withers, 100.7 cm; rump height, 103.1 cm; body length, 103.8 cm; chest circumference, 112.8 cm; chest depth, 45.7 cm; chest width, 29.1 cm; front shin circumference, 13.5 cm; head length, 55 cm; and ear length, 22 cm. The body colour distribution of the donkeys considered in this study was calculated as 39.35% grey, 19.95% white, 21.83% black, and 18.87% brown. Model fit statistics, including the coefficient of determination (R2), mean square error, root-mean-square error (RMSE), mean absolute percentage error (MAPE), and standard deviation ratio (SD ratio), were calculated to measure the predictive ability of the fitted models. The MARS algorithm was found to be the best model for defining the body length of donkeys, with the highest R2 value (0.916) and the lowest RMSE, MAPE, and SD ratio values (2.173, 1.615, and 0.291, respectively). The experimental results indicate that the most suitable model is the MARS algorithm, which provides a good alternative to other data mining algorithms for predicting the body length of donkeys.

6.
Cancers (Basel) ; 15(15)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37568672

RESUMO

Metastatic melanoma is a deadly disease that claims thousands of lives each year despite the introduction of several immunotherapeutic agents into the clinic over the past decade, inspiring the development of novel therapeutics and the exploration of combination therapies. Our investigations target melanin pigment with melanin-specific radiolabeled antibodies as a strategy to treat metastatic melanoma. In this study, a theranostic approach was applied by first labeling a chimeric antibody targeting melanin, c8C3, with the SPECT radionuclide 203Pb for microSPECT/CT imaging of C57Bl6 mice bearing B16-F10 melanoma tumors. Imaging was followed by radioimmunotherapy (RIT), whereby the c8C3 antibody is radiolabeled with a 212Pb/212Bi "in vivo generator", which emits cytotoxic alpha particles. Using microSPECT/CT, we collected sequential images of B16-F10 murine tumors to investigate antibody biodistribution. Treatment with the 212Pb/212Bi-labeled c8C3 antibody demonstrated a dose-response in tumor growth rate in the 5-10 µCi dose range when compared to the untreated and radiolabeled control antibody and a significant prolongation in survival. No hematologic or systemic toxicity of the treatment was observed. However, administration of higher doses resulted in a biphasic tumor dose response, with the efficacy of treatment decreasing when the administered doses exceeded 10 µCi. These results underline the need for more pre-clinical investigation of targeting melanin with 212Pb-labeled antibodies before the clinical utility of such an approach can be assessed.

7.
J Clin Invest ; 133(1)2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36301669

RESUMO

Signaling circuits crucial to systemic physiology are widespread, yet uncovering their molecular underpinnings remains a barrier to understanding the etiology of many metabolic disorders. Here, we identified a copper-linked signaling circuit activated by disruption of mitochondrial function in the murine liver or heart that resulted in atrophy of the spleen and thymus and caused a peripheral white blood cell deficiency. We demonstrated that the leukopenia was caused by α-fetoprotein, which required copper and the cell surface receptor CCR5 to promote white blood cell death. We further showed that α-fetoprotein expression was upregulated in several cell types upon inhibition of oxidative phosphorylation. Collectively, our data argue that α-fetoprotein may be secreted by bioenergetically stressed tissue to suppress the immune system, an effect that may explain the recurrent or chronic infections that are observed in a subset of mitochondrial diseases or in other disorders with secondary mitochondrial dysfunction.


Assuntos
Cobre , Doenças Mitocondriais , Camundongos , Animais , Cobre/metabolismo , alfa-Fetoproteínas/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , Terapia de Imunossupressão
8.
Trop Anim Health Prod ; 44(4): 707-14, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21870064

RESUMO

Water buffalo are an ancient component of Turkey's domestic livestock resources. Commonly referred to as the Anatolian buffalo the animal is part of the Mediterranean group which includes Syrian, Egyptian and Southeast European animals. Once quite numerous, there have been drastic reductions in their numbers since the 1970s due to intensification of dairy activities, agricultural mechanization and changing consumer preferences. The main areas of distribution are in northwest Turkey in the Marmara and Black Sea Regions. Buffalo are kept in small herds by livestock and mixed crop-livestock farmers. Milk is the main product, meat is largely a by-product of the dairy function and provision of the once-important draught power is now a minor output. Buffalo milk is used to prepare a variety of speciality products but output of both milk and meat is very low in comparison to cattle. Conditions of welfare and health status are not optimal. Internal parasites are a constraint on productivity. Some buffalo are being used for conservation grazing in the Black Sea area to maintain optimal conditions for bird life in a nature reserve. Long neglected by government there are recent activities to establish conservation herds, set up in vitro banks and undertake molecular characterization. More effort is needed by government to promote buffalo production and to engage the general public in conservation of their national heritage.


Assuntos
Criação de Animais Domésticos , Búfalos/crescimento & desenvolvimento , Búfalos/genética , Bem-Estar do Animal , Animais , Conservação dos Recursos Naturais , Feminino , Masculino , Carne/normas , Leite/normas , Reprodução , Turquia
9.
J Equine Sci ; 23(4): 47-52, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-24833995

RESUMO

Mules are known to have been used as carriage and riding animals in Mesopotamia and Anatolia as early as the beginning of the second millennium BC but may have been first bred in Anatolia in the Third Century BC. They have thus contributed to Turkey's cultural, social and economic heritage for more than 4,000 years and were an ancient component of its guild of domestic animals and overall biodiversity. Once bred country-wide most mules are now introduced "illegally" to the southeast and east from Iraq and Iran. Mules are now bred only in one small area in north-central Turkey close to the Black Sea. The major role as a pack animal has been usurped since the mid-twentieth century by increasing use of motor transport and numbers have declined rapidly since the early 1980s. In 2009 about 51,500 mules remained in Turkey, mainly distributed in discrete areas in the extreme southeast, the centre-south, the northwest and the centre-north. In the southeast the main role is in cross-border trade (much of it described as smuggling) whereas in other areas mules are used in support of pastoral and farming operations. Mules in Turkey are of various colours but are generally large and strong compared to those found in many other countries. Pressure on numbers will continue and will exert a negative effect on a part of Turkey's national heritage and domestic animal biodiversity.

10.
J Int Adv Otol ; 18(6): 530-536, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36349676

RESUMO

BACKGROUND: The effect of chronic noise on the middle ear is not fully known. This study aimed to evaluate the middle ear functions of metal workers exposed to chronic noise using wideband tympanometry. METHODS: In this study, 62 male workers exposed to chronic noise and 30 healthy men were included. Workers exposed to chronic noise were divided into 2 groups according to their pure tone averages. Totally 30 workers (60 ears) with pure tone average less than 20 dB were included in group I, and 32 workers (64 ears) with pure tone average more than 20 dB were included in group II. All individuals were subjected to wideband tympanometry. Tympanometric peak pressure, equivalent ear canal volume, static acoustic admittance, resonance frequency, and absorbance ratios at peak pressure and ambient pressure values were analyzed. RESULTS: There was no difference between the groups in terms of traditional tympanometric parameters such as tympanometric peak pressure, equivalent ear canal volume, and static acoustic admittance (P >.05). Resonance frequency of workers exposed to chronic noise (group I and group II) was lower than the control group (P <.05). The absorbance ratios of workers exposed to chronic noise at approximately 4 kHz were lower in both peak pressures and ambient pressures (P <.05). CONCLUSION: Chronic noise does not only damage the inner ear but also causes changes in the middle ear structures. Wideband tympanometry can be used to detect minor auditory damage due to noise that cannot be detected by audiogram early. In this way, necessary measures can be taken in the early period before noise-induced hearing loss occurs.


Assuntos
Orelha Interna , Orelha Média , Masculino , Humanos , Testes de Impedância Acústica , Acústica , Meato Acústico Externo
11.
IBRO Neurosci Rep ; 12: 121-130, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35128516

RESUMO

Childhood absence epilepsy (CAE) is a non-convulsive seizure disorder primarily in children characterized by absence seizures. Absence seizures consist of 2.5-5 Hz spike-and-wave discharges (SWDs) detectable using electroencephalography (EEG). Current drug treatments are only partially effective and adverse side effects have spurred research into alternative treatment approaches. Recent research shows that positive allosteric modulation of the type-1 cannabinoid receptor (CB1R) reduces the frequency and duration of SWDs in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a model that recapitulates the SWDs in CAE. Here, we tested additional CB1R ago-PAMs, GAT591 and GAT593, for their potential in alleviating SWD activity in GAERS. In vitro experiments confirm that GAT591 and GAT593 exhibit increased potency and selectivity in cell cultures and behave as CB1R allosteric agonists and PAMs. To assess drug effects on SWDs, bilateral electrodes were surgically implanted in the somatosensory cortices of male GAERS and EEGs recorded for 4 h following systemic administration of GAT591 or GAT593 (1.0, 3.0 and 10.0 mg/kg). Both GAT591 and GAT593 dose-dependently reduced total SWD duration during the recording period. The greatest effect on SWD activity was observed at 10.0 mg/kg doses, with GAT591 and GAT593 reducing seizure duration by 36% and 34% respectively. Taken together, these results support the continued investigation of CB1R PAMs as a potential therapeutic to alleviate SWDs in absence epilepsy.

12.
Turk Arch Otorhinolaryngol ; 60(2): 80-87, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36105523

RESUMO

Objective: To investigate the prognostic value of the magnetic resonance imaging in Bell's palsy patients. Methods: Patients who were diagnosed and treated with Bell's palsy between October 2013 and March 2016 retrospectively selected. House-Brackmann grades, pre- and post-treatment pure tone audiograms, stapedial reflexes were analyzed and magnetic resonance imaging (MRI) scans with gadolinium-based contrast agents were evaluated. Contrast-enhanced segments of the facial nerve were determined. MRI findings were compared statistically with pre- and post-treatment grade, recurrence rate of Bell's palsy, MRI scanning timing, presence of stapes reflexes and posttreatment recovery data. Results: No significant correlation was observed between pretreatment House-Brackmann grades and enhancement (p>0.05). Similarly, there was no significant correlation between clinical recovery and enhancement (p>0.05). Also, no significant correlation was observed between MRI scanning time, the recurrence rate of Bell's palsy and MRI findings (p>0.05). None of the MRIs showed neoplastic contrast enhancement. Conclusion: The routine use of the contrast-enhanced temporal MRI is not recommended in the diagnosis and monitoring of Bell's palsy patients, because the contrast enhancement pattern of the facial nerve has no effect on the prognosis of Bell's palsy. MRI should be used in cases that do not heal despite treatment, for the differential diagnosis of facial nerve tumors and in patients who are candidates for surgical decompression.

13.
Br J Pharmacol ; 176(10): 1455-1469, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29981240

RESUMO

BACKGROUND AND PURPOSE: We sought to understand why (-)-cannabidiol (CBD) and (-)-cannabidiol-dimethylheptyl (CBD-DMH) exhibit distinct pharmacology, despite near identical structures. EXPERIMENTAL APPROACH: HEK293A cells expressing either human type 1 cannabinoid (CB1 ) receptors or CB2 receptors were treated with CBD or CBD-DMH with or without the CB1 and CB2 receptor agonist CP55,940, CB1 receptor allosteric modulator Org27569 or CB2 receptor inverse agonist SR144528. Ligand binding, cAMP levels and ßarrestin1 recruitment were measured. CBD and CBD-DMH binding was simulated with models of human CB1 or CB2 receptors, based on the recently published crystal structures of agonist-bound (5XRA) or antagonist-bound (5TGZ) human CB1 receptors. KEY RESULTS: At CB1 receptors, CBD was a negative allosteric modulator (NAM), and CBD-DMH was a mixed agonist/positive allosteric modulator. CBD and Org27569 shared multiple interacting residues in the antagonist-bound model of CB1 receptors (5TGZ) but shared a binding site with CP55,940 in the agonist-bound model of CB1 receptors (5XRA). The binding site for CBD-DMH in the CB1 receptor models overlapped with CP55,940 and Org27569. At CB2 receptors, CBD was a partial agonist, and CBD-DMH was a positive allosteric modulator of cAMP modulation but a NAM of ßarrestin1 recruitment. CBD, CP55,940 and SR144528 shared a binding site in the CB2 receptor models that was separate from CBD-DMH. CONCLUSION AND IMPLICATIONS: The pharmacological activity of CBD and CBD-DMH in HEK293A cells and their modelled binding sites at CB1 and CB2 receptors may explain their in vivo effects and illuminates the difficulties associated with the development of allosteric modulators for CB1 and CB2 receptors. LINKED ARTICLES: This article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc.


Assuntos
Regulação Alostérica/efeitos dos fármacos , Canabidiol/farmacologia , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Canfanos/farmacologia , Cicloexanóis/farmacologia , Células HEK293 , Humanos , Indóis/farmacologia , Ligantes , Simulação de Acoplamento Molecular , Piperidinas/farmacologia , Ligação Proteica , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/genética , Receptor CB2 de Canabinoide/genética , Transfecção
14.
Noro Psikiyatr Ars ; 54(1): 78-81, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28566964

RESUMO

INTRODUCTION: We aimed to assess central and peripheral nervous system involvement in systemic lupus erythematosus (SLE) patients without any neurological signs and symptoms by performing electrophysiological investigations. METHODS: Thirty-eight SLE patients and 35 healthy volunteers participated in this study. Peripheral nerve conduction and brainstem reflexes were evaluated by performing nerve conduction studies (NCSs) and blink reflex (BR) and masseter inhibitory reflex (MIR) recordings. RESULTS: Eleven patients (29%) had an abnormality in at least 1 NCS parameter, and 1 (2.6%) patient was diagnosed with polyneuropathy. The number of patients with abnormal BR and MIR was 23 (60.5%) and 14 (37%), respectively. The contralateral R2 latency of BR and the silent period 1 (SP1) latency of MIR were significantly prolonged in the patients compared with the controls (p=0.015 and p<0.001, respectively). CONCLUSION: This study showed that irrespective of peripheral nervous system involvement, brainstem reflexes could be affected in SLE patients even without clinical neurological findings. Brainstem reflex abnormalities suggested that the functional integrity of the inhibitory or excitatory interneurons in the lateral caudal pons and lateral medulla is disturbed in SLE patients.

15.
Nat Commun ; 8(1): 786, 2017 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-28983075

RESUMO

Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) channel, which can result in chronic lung disease. The sequence of events leading to lung disease is not fully understood but recent data show that the critical pathogenic event is the loss of the ability to clear bacteria due to abnormal airway surface liquid secretion (ASL). However, whether the inhalation of bacteria triggers ASL secretion and whether this is abnormal in cystic fibrosis has never been tested. Here we show, using a novel synchrotron-based in vivo imaging technique, that wild-type pigs display both a basal and a Toll-like receptor-mediated ASL secretory response to the inhalation of cystic fibrosis relevant bacteria. Both mechanisms fail in CFTR-/- swine, suggesting that cystic fibrosis airways do not respond to inhaled pathogens, thus favoring infection and inflammation that may eventually lead to tissue remodeling and respiratory disease.Cystic fibrosis is caused by mutations in the CFTR chloride channel, leading to reduced airway surface liquid secretion. Here the authors show that exposure to bacteria triggers secretion in wild-type but not in pig models of cystic fibrosis, suggesting an impaired response to pathogens contributes to infection.


Assuntos
Fibrose Cística/metabolismo , Pulmão/metabolismo , Pseudomonas aeruginosa , Mucosa Respiratória/metabolismo , Animais , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Modelos Animais de Doenças , Exposição por Inalação , Pulmão/diagnóstico por imagem , Masculino , Radiografia , Suínos
16.
J Clin Neurol ; 12(2): 166-71, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26790466

RESUMO

BACKGROUND AND PURPOSE: We compared the motor-unit number estimation (MUNE) findings in patients who presented with signs and/or findings associated with carpal tunnel syndrome (CTS) and healthy controls, with the aim of determining if motor-unit loss occurs during the clinically silent period and if there is a correlation between clinical and MUNE findings in CTS patients. METHODS: The study investigated 60 hands of 35 patients with clinical CTS and 60 hands of 34 healthy controls. Routine median and ulnar nerve conduction studies and MUNE analysis according to the multipoint stimulation method were performed. RESULTS: The most common electrophysiological abnormality was reduced conduction velocity in the median sensory nerve (100% of the hands). The MUNE value was significantly lower for the patient group than for the control group (p=0.0001). ROC analysis showed that a MUNE value of 121 was the optimal cutoff for differentiating between patients and controls, with a sensitivity of 63.3% and a specificity of 68.3%. MUNE values were lower in patients with complaints of numbness, pain, and weakness in the median nerve territory (p<0.05, for all comparisons), and lower in patients with hypoesthesia than in patients with normal neurological findings (p=0.023). CONCLUSIONS: The MUNE technique is sensitive in detecting motor nerve involvement in CTS patients who present with sensorial findings, and it may be useful in detecting the loss of motor units during the early stages of CTS. Larger-scale prospective clinical trials assessing the effect of early intervention on the outcome of these patients would help in confirming the possible benefit of detecting subclinical motor-unit loss in CTS.

17.
Surg Laparosc Endosc Percutan Tech ; 15(4): 212-5, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16082308

RESUMO

Laparoscopic splenectomy (LS) is a preferred choice, especially for hematologic diseases. We present the advantages of the use of LigaSure (energy-based equipment that works by applying a precise amount of bipolar energy and pressure to the tissue, achieving a permanent seal) for achieving a precise hemostasis, thus making the LS easier. We have performed LS using LigaSure on 10 patients (4 female, 6 male; mean age, 36 years [range, 16-58]) between December 2002 and August 2003. All patients had ITP. There were no conversion to open surgery. Mean dimensions of spleens were 99 x 49 mm (range, 85 x 36-118 x 60). Intraoperative blood loss was no more than 100 mL in any patients (range, 20-100; mean, 60). The average operative time was 93 minutes (range, 60-155). There were no complications in the postoperative period. The average postoperative stay was 4.3 days (range, 3-7). LS using LigaSure is a safe and time-sparing procedure with almost no complications in this small initial series.


Assuntos
Hemostasia Cirúrgica/instrumentação , Laparoscopia , Esplenectomia/métodos , Adolescente , Adulto , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade
18.
Int. j. morphol ; 35(4): 1502-1511, Dec. 2017. tab
Artigo em Inglês | LILACS | ID: biblio-893162

RESUMO

SUMMARY: The aim of the study was to determine various morphological characteristics from birth to the age of 150th day of Boer x Hair goat F1 crossbred (BH) kids and pure Hair goat (HG) kids raised in semi-intensive conditions and reveal factors such as the effects of genotype, dam age, dam's live weight, year, birth type and sex on this parameter. This study was applied between the years 2011-2012 in Çatak in the Van region and between the years 2013-2014 at the Yuzuncu Yil University Research and Practice Farm. Various body measurements; wither height, back height, rump height, sacrum height, body length, chest length, chest depth, chest circumference, circumference of leg, cannon bone circumference, chest width, front-rump width, mid-rump width were determined 29.8, 28.4, 28.7, 26.2, 28.7, 17.0, 13.3, 30.4, 26.9, 5.2, 5.9, 6.0, and 8.7 cm at birth, respectively; 43.8, 43.8, 44.6, 40.6, 43.6, 22.2, 19.3, 51.7, 41.4, 6.6, 9.2, 9.3, and 11.3 cm at 60th day, respectively; 56.1, 53.4, 54.4, 47.5, 53.3, 27.3, 24.1, 61.4, 49.6, 7.3, 10.6, 11.1, and 13.2 cm at 150th day, respectively for BH kids; 27.3, 25.9, 29.3, 25.3, 27.1, 15.9, 12.3, 29.0, 21.3, 5.1, 5.0, 5.6, and 7.4 cm at birth, respectively; 40.4, 40.1, 42.9, 37.6, 40.5, 22.3, 18.4, 48.1, 36.4, 6.0, 7.9, 9.1, and 10.8 cm at 60th day, respectively; 50.3, 49.2, 51.0, 45.7, 50.4, 27.5, 22.9, 57.3, 43.4, 6.5, 9.5, 10.7, and 11.9 cm at 150th day, respectively for HG kids. When all of the data was considered, it was concluded that the BH kids are much better than the HG kids for both morphological and zoometric values.


RESUMEN: El objetivo del estudio fue determinar varias características morfológicas desde el nacimiento hasta la edad de 150 días en caprinos Boer x Hair goat F1 crossbred (BH) y Cabra pura (HG) criados en condiciones semi-intensivas y revelar factores tales como los efectos del genotipo, la edad, el peso vivo de la el tipo de nacimiento y el sexo entre otros. Este estudio fue realizado entre los años 2011-2012 en Çatak, región de Van y entre los años 2013-2014 en la Granja de Investigación y Práctica de la Universidad Yuzuncu Yil. Se estudiaron diversas medidas corporales: Altura del talón, altura de la espalda, altura de la grupa, altura del sacro, longitud del cuerpo, longitud del pecho, profundidad del tórax, circunferencia del pecho, circunferencia de la pierna, circunferencia del hueso del cañón, ancho del pecho, ancho de la grupa delantera y anchura media de la grupa, así se determinaron 29.8, 28.4, 28.7, 26.2, 28.7, 17.0, 13.3, 30.4, 26.9, 5.2, 5.9, 6.0 y 8.7 cm al nacer, respectivamente; 43.8, 43.8, 44.6, 40.6, 43.6, 22.2, 19.3, 51.7, 41.4, 6.6, 9.2, 9.3 y 11.3 cm en el 60º día, respectivamente; 56.1, 53.4, 54.4, 47.5, 53.3, 27.3, 24.1, 61.4, 49.6, 7.3, 10.6, 11.1 y 13.2 cm en 150 días, respectivamente para niños BH; 27.3, 25.9, 29.3, 25.3, 27.1, 15.9, 12.3, 29.0, 21.3, 5.1, 5.0, 5.6 y 7.4 cm al nacimiento, respectivamente; 40,4, 40,1, 42,9, 37,6, 40,5, 22,3, 18,4, 48,1, 36,4, 6,0,7,9, 9,1 y 10,8 cm en el 60º día, respectivamente; 50.3, 49.2, 51.0, 45.7, 50.4, 27.5, 22.9, 57.3, 43.4, 6.5, 9.5, 10.7 y 11.9 cm a los 150 días, respectivamente, para cabritos HG. Cuando se consideraron todos los datos, se concluyó que los cabritos BH son mucho mejores que los cabritos HG para los valores morfológicos y zoométricos.


Assuntos
Animais , Cabras/anatomia & histologia
19.
Indian J Pharmacol ; 41(3): 120-4, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20442819

RESUMO

OBJECTIVE: The aim of this study was to investigate anti-inflammatory and hepatoprotective activities of Plantago major L. (PM). MATERIALS AND METHODS: Anti-inflammatory activity: Control and reference groups were administered isotonic saline solution (ISS) and indomethacin, respectively. Plantago major groups were injected PM in doses of 5 mg/kg (PM-I), 10 mg/kg (PM-II), 20 mg/kg (PM-III) and 25 mg/kg (PM-IV). Before and three hours after the injections, the volume of right hind-paw of rats was measured using a plethysmometer. HEPATOPROTECTIVE ACTIVITY: The hepatotoxicity was induced by carbon tetrachloride (CCl4) administration. Control, CCl4 and reference groups received isotonic saline solution, CCl4 and silibinin, respectively. Plantago major groups received CCl4 (0.8 ml/kg) and PM in doses of 10, 20 and 25 mg/kg, respectively for seven days. Blood samples and liver were collected on the 8th day after the animals were killed. RESULTS: Plantago major had an anti-inflammatory effect matching to that of control group at doses of 20 and 25 mg/kg. It was found that reduction in the inflammation was 90.01% with indomethacin, 3.10% with PM-I, 41.56% with PM-II, 45.87% with PM-III and 49.76% with PM-IV. Median effective dose (ED50) value of PM was found to be 7.507 mg/kg. Plantago major (25 mg/kg) significantly reduced the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels when compared to the CCl4 group. The histopathological findings showed a significant difference between the PM (25 mg/kg) and CCl4 groups. CONCLUSION: The results showed that PM had a considerable anti-inflammatory and hepatoprotective activities.

20.
Recent Pat Antiinfect Drug Discov ; 3(2): 149-52, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18673129

RESUMO

This study was performed to investigate the anthelmentic (nematodes) effect of garlic in Swiss albino mice naturally infected with Aspiculuris tetraptera. Natural infection was determined by the use of cellophane tape method on the perianal region and by the technique of centrifugal flotation of stool samples. The infected mice were divided into three groups; namely, Group 1: garlic treatment groups (n: 18), Group 2: positive control (treated with ivermectin, n: 19) and Group 3: untreated control group (n: 19). The mice in Group 1 were given orally freshly crushed garlic homogenates every day for 7 days. The animals in Group 2 were treated with ivermectin intramuscular at a dose of 0.2 mg/kg body weight. The mice in Group 3 received only serum physiologic orally. After 8 days of administrations, all mice were killed humanely using inhalation anaesthesia and then the parasites in the intestine were counted. It was observed that garlic and ivermectin were 91.24 % and 78.03 % effective against A. tetraptera in naturally infected mice, respectively. Results obtained from this study were compared statistically and differences were found to be significant (p<0.001). It was found that garlic was efficient along the duration of the treatment in mice. Garlic may be useful as an alternative treatment against nematode parasites in animals and human. This article includes a new research using Allium sativum anthelmentic effect on mouse and has been patented.


Assuntos
Anti-Helmínticos/farmacologia , Alho , Intestinos/efeitos dos fármacos , Oxiuríase/tratamento farmacológico , Doenças dos Roedores/tratamento farmacológico , Administração Oral , Animais , Anti-Helmínticos/administração & dosagem , Injeções Intramusculares , Intestinos/parasitologia , Ivermectina/farmacologia , Masculino , Camundongos , Oxiuríase/parasitologia , Oxiuríase/veterinária , Patentes como Assunto , Preparações de Plantas/farmacologia , Doenças dos Roedores/parasitologia
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