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PURPOSE: Determine stones composition of the upper urinary tract in the eastern region of Algeria. METHODS: Our study focuses on a set of 359 stones of the upper urinary tract collected between January 2007 and December 2012 at hospitals in the eastern region of Algeria and analyzed by Fourier transform infrared spectroscopy. RESULTS: The male/female ratio was only 1.32. Calcium oxalate prevailed in 68.5% of stones and 49.3% of nuclei, mainly as whewellite (51.8% of stones and 37.9% of nuclei vs 16.7% and 11.4% respectively for weddellite). Carbapatite prevailed in 15% of stones and 29.8% of nuclei. The struvite, identified in 11.1% of calculi, prevailed in 3.9% of stones and 3.1% of nuclei. Among purines, uric acid prevailed with frequencies quite close to 8.9% and 7% respectively in the stone and in the nucleus while the ammonium urate prevailed in only 0.3% of stones and 3.3% of nuclei. The cystine frequency was 3.6% in both stone and nucleus. The frequency of stone with umbilication was 26.2%. Whewellite was the main component of umbilicated stones with Randall's plaque. CONCLUSION: Our results suggest that stones of the urinary tract in the Algerian east region resemble those observed in industrialized countries. Some features such as stones location, the whewellite prevalence, the frequencies of main components in both the stone and the nucleus as well as the formation of stones on renal papilla confirm this trend. LEVEL OF EVIDENCE: 4.
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Oxalato de Calcio/análisis , Cálculos Renales/química , Cálculos Renales/epidemiología , Adulto , Anciano , Argelia/epidemiología , Antioxidantes/análisis , Apatitas/análisis , Femenino , Hemostáticos/análisis , Hospitales/estadística & datos numéricos , Humanos , Compuestos de Magnesio/análisis , Masculino , Persona de Mediana Edad , Fosfatos/análisis , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Estruvita , Ácido Úrico/análisisRESUMEN
Anurans from terrestrial environments have an enhanced ability to maintain mean arterial blood pressure (Pm) through lymph mobilization in response to desiccation or hemorrhage compared with semiaquatic or aquatic species. Because short term blood pressure homeostasis is regulated by arterial baroreceptors, we compared baroreflex function in three species of anurans that span a range of environments, dehydration tolerance and an ability to maintain Pm with dehydration and hemorrhage. The cardiac limb of the baroreflex loop was studied using pharmacological manipulation of Pm with phenylephrine and sodium nitroprusside (20-200µgkg(-1)), and the resulting changes in heart rate (fH) were quantitatively analyzed using a four-parameter sigmoidal logistic function. Resting Pm in the aquatic species, Xenopus laevis, was 3.6±0.3kPa and was significantly less (P<0.005) than for the semiaquatic species, Lithobates catesbeianus (4.1±0.2kPa), or the terrestrial species, Rhinella marina (4.7±0.2kPa). The maximal baroreflex gain was not different among the three species and ranged from 12.1 to 14.3beatsmin(-1)kPa(-1) and occurred at Pm ranging from 3.0 to 3.8kPa, which were slightly below the resting Pm for each species. Mean arterial blood pressures at rest in the three species were near the saturation point of the baroreflex curve which provides the animals with a greater fH response range to hypotensive, rather than hypertensive, changes in Pm. This is consistent with the hypothesis that arterial baroreceptors are key sensory components that allow anurans to maintain Pm possibly by mobilization of lymphatic return in response to hypotension.
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Anuros/fisiología , Barorreflejo/fisiología , Animales , Barorreflejo/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Bufo marinus/fisiología , Ambiente , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Sistema Linfático/fisiología , Nitroprusiato/farmacología , Fenilefrina/farmacología , Rana catesbeiana/fisiología , Especificidad de la Especie , Xenopus laevis/fisiologíaRESUMEN
Anurans from terrestrial environments have an enhanced ability to maintain mean arterial blood pressure (P(m)) through lymph mobilization in response to desiccation or hemorrhage compared with semiaquatic or aquatic species. Because short term blood pressure homeostasis is regulated by arterial baroreceptors, we compared baroreflex function in three species of anurans that span a range of environments, dehydration tolerance and an ability to maintain P(m) with dehydration and hemorrhage. The cardiac limb of the baroreflex loop was studied using pharmacological manipulation of P(m) with phenylephrine and sodium nitroprusside (20200 µg kg(− 1)), and the resulting changes in heart rate (f(H)) were quantitatively analyzed using a four-parameter sigmoidal logistic function. Resting P(m) in the aquatic species, Xenopus laevis, was 3.6 ± 0.3 kPa and was significantly less (P < 0.005) than for the semiaquatic species, Lithobates catesbeianus (4.1 ± 0.2 kPa), or the terrestrial species, Rhinella marina (4.7 ± 0.2 kPa). The maximal baroreflex gain was not different among the three species and ranged from 12.1 to 14.3 beats min( −1) kPa( −1) and occurred at P(m )ranging from 3.0 to 3.8 kPa, which were slightly below the resting P(m) for each species. Mean arterial blood pressures at rest in the three species were near the saturation point of the baroreflex curve which provides the animals with a greater fH response range to hypotensive, rather than hypertensive, changes in P(m). This is consistent with the hypothesis that arterial baroreceptors are key sensory components that allow anurans to maintain P(m) possibly by mobilization of lymphatic return in response to hypotension.
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Anuros/fisiología , Barorreflejo/fisiología , Ambiente , Animales , Barorreflejo/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Bufo marinus/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Nitroprusiato/administración & dosificación , Nitroprusiato/farmacología , Especificidad de la Especie , Xenopus/fisiologíaRESUMEN
INTRODUCTION: Episiotomy, despite being one of the most common interventions during childbirth, carries significant risks and uncertain benefits. Previous global studies highlight varying awareness levels and practices, with decreasing episiotomy rates attributed to increased knowledge. This study aims to assess women's knowledge to enhance intrapartum decision-making and communication between patients and obstetricians, ultimately improving maternal outcomes in the region. METHODOLOGY: The study was a cross-section design. It was conducted through an online survey that was distributed by different social media platforms (Twitter, WhatsApp, and Telegram) from February 2023 to January 2024. It included women living in the Qassim region, Saudi Arabia, who were 15 years old or older. Data was analyzed using the SPSS program (IBM, Chicago, Illinois, USA). RESULTS: Among the 402 participants, 62.7% demonstrated awareness of episiotomy, with 94.0% accurately identifying it as a surgical cutting with scissors. About 82.5% acknowledged that not all women require episiotomies, while 48.8% recognized the necessity of anesthesia before the procedure. Understanding the indications for episiotomy varied, with facilitating and accelerating childbirth (64.3%) and dealing with a large baby (62.3%) being the most recognized reasons. Impressively, 90.5% believed that there are methods to avoid perineal cutting, with knowing the correct mechanism for pushing during childbirth (69.4%) and exercise (54.4%) being the most acknowledged preventive measures. Regarding post-cutting care, antibiotics (61.5%) were identified as essential, followed by analgesia (52.8%) and laxatives (48.8%). CONCLUSION: The study reveals a notable awareness among participants, with a majority demonstrating a solid understanding of the procedure, its indications, and post-procedure care. It identified specific knowledge gaps, such as the need for anesthesia awareness and divergent beliefs about post-episiotomy care practices.
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OBJECTIVE: Sepsis-associated liver injury is responsible for the high morbidity and mortality rates seen with septic shock. Activation of the renin-angiotensin-aldosterone system (RAAS) is an essential counteractive mechanism during the hypotensive phase of sepsis; however, excessive activation is associated with exaggerated pro-oxidant and inflammatory response, which aggravates organ damage. This study aimed to evaluate the effect of RAAS inhibition on sepsis-induced liver damage. MATERIALS AND METHODS: The cecal ligation and puncture (CLP) model was employed as a model of sepsis. Rats were divided into five groups: sham-operated, vehicle-treated septic rats, septic rats treated with ramipril in a dose of 10 mg/kg, septic rats treated with losartan in a dose of 20 mg/kg, and finally septic rats treated with spironolactone in a dose of 25 mg/kg. Rats received the treatment one hour after induction. Twenty-four hours later, rats were euthanized, and serum samples and liver tissue were collected to evaluate liver function and hepatic oxidative, anti-oxidative, inflammatory, and apoptotic markers. The microscopic integrity of the hepatic tissue was also assessed. RESULTS: The results of our study showed that all the treatments used ameliorated sepsis-induced liver injury. This was reflected by improved liver function parameters and histopathological appearance of liver tissue. Treatment with ramipril, losartan, or spironolactone reduced tissue malondialdehyde (MDA), nitric oxide, activated caspase-3, and TNF-α. Moreover, these drugs increased hepatic reduced-glutathione (GSH) levels, superoxide dismutase (SOD) activity, and proliferating cell nuclear antigen (PCNA) expression. CONCLUSIONS: Administration of ramipril, losartan, or spironolactone after CLP produced a hepatoprotective effect in rats, possibly by reducing oxidative stress, inflammation, and apoptosis.
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Losartán , Sepsis , Animales , Ratas , Losartán/farmacología , Losartán/uso terapéutico , Ramipril/farmacología , Ramipril/uso terapéutico , Espironolactona/farmacología , Espironolactona/uso terapéutico , Punciones , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , HígadoRESUMEN
INTRODUCTION: Anaphylaxis is described as a severe allergic reaction, and prompt assistance is required by the patient to avoid any complications. The healthcare provider's knowledge plays an important role in the diagnosis and treatment of these cases. The aim of this study was to evaluate the knowledge among the primary healthcare providers working in the Qassim region of Saudi Arabia regarding the diagnosis and treatment of anaphylaxis. METHOD: This cross-sectional study was conducted in the four different governments of the Qassim region of Saudi Arabia. The calculated sample size for the study was 119 primary healthcare providers. A self-administered questionnaire was devised to collect data regarding the diagnosis and treatment of anaphylaxis patients. RESULTS: Thirty-six (28.8%) out of 119 physicians were 25-30 years old, followed by 33 (26.4%) who were more than 40 years old; 53 (42.4%) and 47 (36.7%) had less than five and more than 10 years of experience, respectively. Age and experience were found to be significantly associated with knowledge about the diagnostic criterion (p=0.003 and p=0.000, respectively), while experience was significantly associated with the correct identification of signs and symptoms (p=0.031). CONCLUSION: Knowledge about the diagnosis and management of anaphylaxis patients among primary healthcare providers was poor. Physicians are required to be educated to increase their level of knowledge to promptly diagnose and treat anaphylaxis cases.
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BACKGROUND: Cow's milk allergy (CMA) typically first manifests in the first year of life, and it is the most challenging food allergy to detect since the clinical symptoms can vary significantly in both types and severity. This study is carried out to evaluate the level of knowledge and practice of healthcare providers (HCPs) in the Qassim Region regarding CMA. RESEARCH METHODOLOGY: This is a cross-sectional study conducted among HCPs in the Qassim Region, Saudi Arabia. A self-administered questionnaire was distributed among HCPs using face-to-face interviews compromising four governorates of Qassim such as Buraydah, Unaizah, AlRass, and Albukairyah. The questionnaire includes socio-demographic characteristics and questions to assess the knowledge and practice of HCPs regarding CMA. RESULTS: Among 124 HCPs, 29% were aged between 25 and 30 years, 50.8% were males and 49.2% were females. Over three-quarters (77.4%) were categorized as having poor knowledge levels, while poor practice was also prevalent (83.1%). Factors associated with increased knowledge and practice were being non-Saudi, being a consultant/specialist, and having more than 10 years of experience. There was a significant positive correlation between knowledge and practice scores (p<0.001). CONCLUSION: The knowledge and practice of HCPs regarding CMA were insufficient. Non-Saudi consultants/specialists with more years of experience tend to be more knowledgeable and have better skills in managing the disease. Further longitudinal studies are required to establish the level of knowledge and practices toward CMA.
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Status epilepticus is a neurological emergency associated with high morbidity and mortality with fatal outcomes if not treated well. The goal of this study was to compare the intramuscular and intravenous treatment of individuals with status epilepticus. A search was performed on Scopus, PubMed, Embase, and Web of Science databases for articles published in the English language in peer-reviewed publications up to March 1, 2023. Studies were included if the treatment of status epileptics was compared either directly or indirectly between intramuscular and intravenous methods. In addition, relevant papers were manually screened for in the reference lists of the included studies. Non-duplicate articles were identified. Finally, five articles were included in the analysis, of which four were randomized controlled trials and one was a retrospective cohort study. The intramuscular midazolam group's time until the first seizure stopped was significantly shorter than the intravenous diazepam group's time (7.8 versus 11.2 minutes, respectively; p = 0.047). Moreover, the percentage of patients admitted was significantly lower in the intramuscular group than in the intravenous group (p = 0.01), but the lengths of stay in the intensive care unit and the hospital did not differ significantly between the groups. Regarding seizure recurrence, the intramuscular group had fewer incidences of recurrent seizures. Finally, there were no appreciable differences in safety outcomes between the two treatment arms. During the analysis, different outcomes reported after the use of intramuscular and intravenous treatments in managing patients with status epilepticus were categorized. This categorization led to a clear view of the efficacy and safety of intramuscular versus intravenous treatments in managing status epilepticus patients. The information at hand indicates that intramuscular therapy is just as successful as intravenous therapy in treating people with status epilepticus. The availability, adverse effect profile, logistics of administration, cost, and whether it is included in hospital formularies are some of the factors to be taken into consideration when choosing the drug administration technique.
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BACKGROUND: Headaches are a common complaint among asthma patients. However, there is no study to assess the relationship between asthma and headaches or to assess the prevalence of headaches among asthma patients in Saudi Arabia. We aim to study the relationship between asthma and headaches and also to assess the prevalence of headaches among asthma patients. RESEARCH METHODOLOGY: We conducted a cross-sectional study among 528 asthmatic patients. Participants were selected through non-probability sampling from the system of four hospitals (King Fahad Specialist Hospital, King Saud Hospital, Buraidah Central Hospital, and Qassim University Hospital). The duration of our study was one year from 11 September 2022 to 14 May 2023. Data collection was performed by using a pre-tested and self-administered questionnaire. Data were analyzed through IBM SPSS Statistics for Windows, Version 24 (Released 2016; IBM Corp., Armonk, New York, United States) by using the chi-square test to assess the relationship between the qualitative variables and independent t-test and ANOVA for comparing the quantitative variables with a significant level set at p-value < 0.05. RESULTS: Five hundred and twenty-eight asthmatics were studied for demographics, asthma management, and headaches. Most of the patients were male, married, and university-educated. Sixty-one percent had uncontrolled asthma, and 47.3 percent of individuals had headaches, mostly migraines. Uncontrolled asthma was linked to greater headache prevalence. Gender, educational level, and headache type did not affect headache prevalence in demographic and asthma control subgroups. Co-occurring asthma and migraines may benefit from asthma control and treatment. CONCLUSION: The research emphasizes the significant frequency of uncontrolled asthma and headaches among asthmatic patients. The association between asthma control and headache prevalence was statistically significant, highlighting the necessity for appropriate management and treatment techniques for both disorders. These findings have significant implications for health care providers and politicians seeking to improve the quality of life for those with asthma and co-occurring headaches.
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Introduction Short stature is a common reason for referral to pediatric endocrinologists. A Saudi study highlights significant short stature prevalence, with parents exhibiting varied knowledge levels. Common normal variants of short stature are familial short stature, constitutional, and idiopathic short stature. Pathologic causes of short stature include growth hormone deficiency, genetic disorders, and chronic diseases. Parents' knowledge plays an important role in the diagnosis and early intervention of this condition. Insufficient studies prompt the authors to conduct a novel survey assessing Saudi parents' knowledge and perceptions of short stature, filling a research gap. Methodology This is a cross-sectional study conducted among Saudi Parents in five different regions of Saudi Arabia. A self-administered questionnaire was distributed among parents via an online survey. The questionnaire includes sociodemographic characteristics and questions to assess the knowledge and perception regarding short stature. Non-probability sampling targets parents living in Saudi Arabia. Data is analyzed by SPSS version 29 (IBM Inc., Armonk, New York). Results Our study on Saudi parents' knowledge of short stature reveals diverse awareness levels. While genetic causes are widely recognized in (71.6%; N=245) of parents (N=352), awareness drops for factors like low birth weight (23.9%; N=82) total of (N=352). Parents show uncertainty in recognizing short stature (51.4%; N=352) and varied beliefs on growth cessation. A majority (65.6%; N=231) of parents (N=352) prefer early intervention, with 41.5% (N=146) of parents (N=352) recognizing growth hormone therapy. Sociodemographic factors influence knowledge scores, with higher scores in males (21.03) and Central region residents (22.03; p<0.001). Notably, 83.4% (N=248) of parents (N=352) acknowledge psychological complications. Conclusion Our study highlights varied awareness among parents regarding short stature, emphasizing genetic causes but demonstrating gaps in recognizing certain factors. Sociodemographic factors significantly influence knowledge scores. Psychological complications are widely acknowledged.
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BACKGROUND: Cerebral palsy is a heterogeneous group of permanent non-progressive disorders affecting the development of movement and posture, varying in severity, interfering with daily activity, and associated with multiple comorbidities. Previous studies in different regions of Saudi Arabia have shown links between caregivers' mental health and children's well-being. However, the lack of such research in the Tabuk region necessitates the development of a new survey to assess caregivers' quality of life in this specific area. METHODOLOGY: This was a cross-sectional study, conducted during 2022-2023. It included the caregivers of Saudi children with cerebral palsy in the Tabuk region. Data was collected using an online questionnaire and was analyzed using the SPSS program (IBM Corp., Armonk, NY). RESULTS: The study included 63 participants. Mothers (50.8%) and fathers (46.0%) were the primary caregivers. The comorbidities of cerebral palsy children like seizures (28.6%) and learning difficulties (19.0%) were prevalent for cerebral palsy children. Around 20.6% of participants received home health care. In terms of family quality of life, the majority expressed satisfaction with family interaction, parenting, and emotional well-being, although mixed feelings were observed. CONCLUSION: The majority of caregivers reported satisfaction in various domains of family quality of life, particularly in family interaction and parenting. However, a notable percentage expressed dissatisfaction in some areas, highlighting the complex emotional and practical challenges faced by these caregivers.
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Experimental hyperlipidemia has shown to decrease cytochrome P450 3A4 and 2C11 expression and to increase liver concentrations and the plasma protein binding of halofantrine (HF) enantiomers. The present study examined the effect of hyperlipidemic (HL) serum on the metabolism of HF enantiomers by primary rat hepatocytes. Hepatocytes from normolipidemic (NL) and HL (poloxamer 407 treated) rats were incubated with rac-HF in cell media with or without additional rat serum (5%). In those incubations with rat serum, the hepatocytes were preincubated or coincubated with serum from NL or HL rats. Rat serum-free hepatocyte incubations served as controls. Stereospecific assays were used to measure HF and desbutylhalofantrine (its major metabolite) enantiomer concentrations in whole well contents (cells + media). Concentrations of desbutylhalofantrine were not measurable. The disappearance (apparent metabolism) of (-)-HF exceeded that of antipode, but HF metabolism did not differ between hepatocytes from NL and HL rats. Coincubation of HL rat serum with NL hepatocytes caused a significant decrease in the disappearance of (-)-HF, whereas in HL hepatocytes, a substantially decreased apparent metabolism was noted for both enantiomers. Compared with NL serum, (-)-HF disappearance was significantly lowered upon preincubation of NL hepatocytes with HL serum. A combination of factors including diminished drug metabolizing or lipoprotein receptor expression, and increased plasma protein binding in the wells, may have contributed to a decrease in apparent metabolism of the HF enantiomers in the presence of lipoproteins from HL rat serum.
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Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Lipoproteínas/sangre , Lipoproteínas/farmacología , Fenantrenos/química , Fenantrenos/metabolismo , Animales , Antimaláricos/química , Antimaláricos/metabolismo , Hiperlipidemias/sangre , Hiperlipidemias/metabolismo , Ratas , Ratas Sprague-Dawley , EstereoisomerismoRESUMEN
This study was performed to investigate the bioequivalence of cefuroxime axetil tablets between a generic test product (A) Zednad® Tablet (500 mg cefuroxime/ tablet, Diamond Pharma, Syria), and the Reference Product (B) Zinnat® Tablet (500 mg cefuroxime/tablet, GlaxoSmithKline, Saudi Arabia). The bioavailability study was carried out for 24 healthy male volunteers. The subjects received 1 Zednad® Tablet (500 mg/ tablet) and 1 Zinnat® Tablet (500 mg/tablet) in a randomized, two-way crossover design fashion on 2 treatment days, after an overnight fast of at least 10 h, with a washout period of 7 days. 24 volunteers plus 2 alternatives completed the crossover. The bioanalysis of clinical plasma samples was accomplished by HPLC method, which was developed and validated in accordance with international guidelines. Pharmacokinetic parameters, determined by standard non-compartmental methods, and ANOVA statistics were calculated using SAS Statistical Software. The significance of a sequence effect was tested using the subjects nested in sequence as the error term. The 90% confidence intervals for the ratio between the test and reference product pharmacokinetic parameters of AUC0ât, AUC0â∞, and Cmax were calculated and found to be within the confidence limits of 80.00 - 125.00% for AUC0ât, AUC0â∞ and Cmax. The study demonstrated that the test product (A) was found bioequivalent to the reference product (B) following an oral dose of 500 mg tablet. Therefore, the two formulations were considered to be bioequivalent.
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Antibacterianos/farmacocinética , Cefuroxima/análogos & derivados , Adulto , Área Bajo la Curva , Disponibilidad Biológica , Cefuroxima/administración & dosificación , Cefuroxima/farmacocinética , Química Farmacéutica , Estudios Cruzados , Humanos , Masculino , Comprimidos , Equivalencia TerapéuticaRESUMEN
PURPOSE: To determine the value of Power Doppler US for the diagnosis of prostate cancer and in the prediction of cancer aggressiveness. PATIENTS AND METHODS: One hundred and five consecutive patients with PSA>4 ng/ml and/or abnormal digital rectal exam underwent power Doppler US prior to biopsy. In addition to biopsies directed to suspiscious lesion on US, 10 to 12 standard sextant biopsies were obtained. Histologic results were correlated to imaging findings. RESULTS: A hypervascular lesion (enlarged, irregular, serpentine or disorganized vessels) was present at power Doppler US in 34 patients and corresponded to cancer in 28 cases. Nineteen cancers showed no detectable abnormality on power Doppler US. Cancer was present in 271 of 1093 cores. After correlation with results from sextant prostate biopsy, power Doppler showed a sensitivity of 44%, specificity of 96%, positive predictive value of 84% and negative predictive value of 80%. Positive results on power Doppler US were strongly cotrrelated with higher Gleason scores. CONCLUSION: Power Doppler US may contribute to the evaluation of prostate cancer aggressiveness and direct biopsies to more aggressive foci.
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Neoplasias de la Próstata/diagnóstico por imagen , Ultrasonografía Doppler/métodos , Anciano , Anciano de 80 o más Años , Biopsia , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Próstata/patología , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Sensibilidad y EspecificidadRESUMEN
High-voltage electrical burn injuries are rare emergencies in pediatric units and always associated with a poor prognosis. Recklessness, lack of knowledge about electric currents and the lack of safety around public electricity infrastructures are the three main factors contributing to the occurrence of high-voltage electrical accidents in children. Mortality is due to acute cardiac and renal complications, and trauma associated with falls. Secondary evolution is dominated by the risk of infection and the severity of functional sequelae. Early diagnosis and prompt treatment is needed to prevent these complications. Therapeutic management is based on early resuscitation and surgical management of tissue damage. We report three cases of high-voltage electrocution in children, with electro-thermal burns associated with severe head injury in one case, and myocardial damage and a compartment syndrome with severe functional sequelae in the other two. These three case reports are an opportunity to discuss literature data.
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Tissue engineering requires the response of the cells to different stimuli inducing the synthesis of the extracellular matrix (ECM). It was been shown that mechanical and biochemical stimuli acted on the synthesis of ECM, particularly type I and III collagens. Growth factors implied in transduction pathways are multiple, but the main is TGF-beta. Member of the transforming growth factor-beta (TGF-beta) family bind to type II and type I serine/threonine kinase receptors, which initiate intracellular signals through activation of SMADs proteins. Nevertheless, the effects of mechanical stress of this pathway remain unknown. The aim of this work was to study the pathway of TGF-beta via the SMADs proteins under mechanical (stretching) and biochemical (TGF-beta) stimulations. Endogenous SMADs expression and its modulation by biochemical and mechanical stimulations were evaluated by both flow cytometry and confocal microscopy. Our results demonstrate that 10 ng of TGF-beta and stretching (5%, 1 Hz) applied during 15 min induced a negative feed back loop which blocks the signalling pathway to control TGF-beta activity. This inhibition effect was raised after 1 h of stimulation. Nevertheless, these preliminary studies should be continued by study of expression and localization of inhibitory SMADs (SMAD7).
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Mecanotransducción Celular/fisiología , Estimulación Física/métodos , Transducción de Señal/fisiología , Proteínas Smad/metabolismo , Ingeniería de Tejidos/métodos , Factor de Crecimiento Transformador beta/farmacología , Línea Celular , Elasticidad , Humanos , Mecanotransducción Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Estrés MecánicoRESUMEN
In tissue engineering, surface characteristics of a biomaterial are one of most important factors determining the compatibility with the environment. They influence attachment and growth of cells onto the material. In many cases, the surface should to be modified and engineered in the desired direction. The modification of non-adhesive surfaces with polyelectrolyte multilayer films (PMF) was recently depicted as a powerful technique to promote the growth of different cell lines. In this study, we evaluated the possible use of two different PMF as surface modification for the culture of mesenchymal stem cells (MSC). We used two types of PMF which differed by the nature of the initial anchoring layer which was poly(ethylenimine) (PEI) or poly(allylamine hydrochloride) (PAH). This initial polyelectrolytes adsorption was followed by the alternated deposition of poly(sodium 4-styrenesulfonate) (PSS) and (PAH) in order to obtain a PEI-(PSS-PAH)(3) film or a PAH-(PSS-PAH)(3) film. In order to control the behaviour of MSC, the cell viability was evaluated by Alamar Blue assay and the actin cytoskeleton was labelled and visualised in a confocal microscope. The behaviour of cells on the two PMF was compared to cells cultivated on surfaces treated with fibronectin. The results showed that PAH-(PSS-PAH)(3) PMF improve the growth of cells, inducing a higher cell viability compared to PEI-(PSS-PAH)(3) PMF and fibronectin at 2, 3 and 7 days of culture. Moreover, those cells showed a well-organized actin cytoskeleton. In conclusion, PAH-(PSS-PAH)(3) polyelectrolyte multilayer film seems to constitute an excellent material for MSC seeding.
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Materiales Biocompatibles/química , Técnicas de Cultivo de Célula/métodos , Membranas Artificiales , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Ingeniería de Tejidos/métodos , Adhesión Celular/fisiología , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Humanos , Ensayo de Materiales , Propiedades de SuperficieRESUMEN
This study was done to compare the bioavailability of a new tablet formulation of gemifloxacin (gemifloxacin 320 mg/tablet) with that of the reference product (factive 320 mg/tablet). The bioequivalence of a single dose (320 mg) was assessed for gemifloxacin included in the test and reference products by comparing the pharmacokinetic parameters derived from the plasma concentration-time profiles following administration to 24 healthy male volunteers in a balanced, 2-period, 2-sequence, 2-way crossover design. Plasma concentrations of gemifloxacin were analyzed by a validated and sensitive HPLC assay developed in-house. The mean plasma concentration-time profiles are almost superimposable. 18 ANOVAs were performed to compare gemifloxacin plasma levels of the two formulations at each sampling time and there were no statistical differences between the two formulations. The parameters used to measure bioavailability were AUC0-t, AUC0-infinity and Cmax and they were calculated by a model-independent method. The parametric 90% confidence intervals of the mean values for the test/reference ratio were in each case well within the bioequivalence acceptable boundaries of 80-125% for AUCo-t, AUC0-infinity and Cmax. Data obtained in this study prove, by appropriate statistical methods, the essential similarity of plasma levels of gemifloxacin from the test product with those from the reference product suggesting equal clinical efficacy of these two products.
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Medicamentos Genéricos/farmacocinética , Fluoroquinolonas/farmacocinética , Naftiridinas/farmacocinética , Adulto , Análisis de Varianza , Antibacterianos/sangre , Antibacterianos/farmacocinética , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Ciprofloxacina/sangre , Ciprofloxacina/farmacocinética , Ciprofloxacina/normas , Estudios Cruzados , Fluoroquinolonas/sangre , Gemifloxacina , Semivida , Humanos , Masculino , Naftiridinas/sangre , Estándares de Referencia , Comprimidos , Equivalencia TerapéuticaRESUMEN
Endothelial cells (ECs) which participate the interface between the blood and the vessel wall undergo morphologic changes in response to shear stress induced by blood flow, liable for the important regulation on physiologic and pathophysiologic function of blood vessels. Shear stress induced changes in cell morphology, begin with elongation in the direction of shearing and end by a reorientation and assembly of F-actin stress fibers. Shear stress is also implicated in many important ECs functions such as: decrease of platelet aggregation, anti-thrombogenic and anti-adhesive effects, inhibition of vascular smooth muscle cell (SMC) proliferation and regulation of their contraction and arterial tonicity, via a regulation of vasodilator and vasoconstrictor secretion molecules such as nitric oxide (NO), endothelin I, prostacyclin and angiotensin II. Besides, many of human diseases such as hypercholesterolemia, diabetes and hypertension, are strongly linked to a disturbance of the production of several vasodilator or vasoconstrictor molecules. The aim of this in-vitro study was to evaluate the potential balance between time and rate effects of shearing in cell shape changes and e-NOS activity. Two unidirectional steady laminar flow rates (1.2 Pa and 2.0 Pa) were applied on EC monolayers, each one for a short and a long period, (6 h and 24 h). Cytoskeleton reorganization was evaluated by actin filaments labelling and observed by confocal microscopy. NO production was evaluated by a colorimetric method using the Griess reagent kit for nitrite determination. Results showed that laminar flow affected cell rearrangement by inducing cytoskeleton reorientation and increased production of NO. Laminar shear rate at 2.0 Pa for 24 h did not upregulate NO release. Whereas at 1.2 Pa for 24 h, NO release increased by 33% compared with the static conditions. Both 1.2 Pa and 2.0 Pa for 6 h increased NO release by 17% and 24% respectively as compared with the static conditions. These observations suggested that stress fiber assembly, which controls EC reorientation and NO production, are dependent on rate and time of shearing. In addition, there appear to be a relation between the cytoskeleton reorganization stage and NO production. These results could promote the parameters to evaluate the more appropriate pattern of shearing, to evaluate a potential pharmacological effect on hypertension disorder decrease.
Asunto(s)
Citoesqueleto/metabolismo , Endotelio Vascular/citología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Citoesqueleto de Actina/metabolismo , Forma de la Célula , Células Cultivadas , Citoesqueleto/ultraestructura , Células Endoteliales/citología , Células Endoteliales/metabolismo , Células Endoteliales/ultraestructura , Humanos , Óxido Nítrico/análisis , Óxido Nítrico/biosíntesis , Estrés Mecánico , Venas Umbilicales/citologíaRESUMEN
Vascular endothelial cells form a monocellular layer on blood vessel walls with an estimated mass of 1.5 kg. One of the roles of endothelial cells is to control the hemodynamics through various metabolic activities affecting homeostasis, vascular tonus, blood fluidity, coagulating properties and blood cell adhesion. In other respects thousands of studies have underlined the crucial role of local blood flow conditions on their properties. However, the hemodynamic forces are different according to the anatomical site and to the type of blood vessels (arteries, veins, venules, ...). In microcirculation, the endothelial cells in the venules are particularly active and constitute the physiological site of liquid exchange (permeability) and above all cellular transit. During critical ischemia, the post-capillary venules are deeply involved. In other respects the properties of endothelial cells may be impaired in many diseases as atherosclerosis, hypertension, inflammation and metabolic diseases.