Low-Frequency Magnetic Stimulation of Shenmen Acupoint Reduces Blood Oxygen Levels in the Prefrontal Cortex of Healthy Subjects: A Near-Infrared Brain Functional Imaging Study / 中国结合医学杂志

OBJECTIVE@#To explore the effect of low-frequency magnetic stimulation at Shenmen (HT 7) acupoint on blood oxygen levels in the prefrontal cortex of healthy subjects.@*METHODS@#Functional near-infrared spectroscopy (fNIRS) technology was used to collect real-time data of oxygenated hemoglobin (oxy-Hb) in the prefrontal cortex of 16 healthy subjects at resting state and low-frequency magnetic stimulation of Shenmen. The mean and integral values of blood oxygen concentration were analyzed.@*RESULTS@#Compared with the resting state, the mean and integral values of blood oxygen concentration were decreased during the task period, recovery period, and the whole process in the magnetic stimulation of Shenmen acupoint (P<0.05). In particular, the difference was statistically significant in the recovery period (P<0.01).@*CONCLUSIONS@#The prefrontal cortex was widely activated and produced an immediate effect by reducing the local blood oxygen concentration at low-frequency magnetic stimulation of Shenmen acupoint, which verifies the sedative effect of Shenmen acupoint.

Clinical pharmacokinetics of Ginkgolides Dropping Pills in healthy subjects / 中草药

Objective: In order to describe the pharmacokinetic profiles of two effective constituents ginkgolide A and ginkgolide B in healthy subjects, and to provide supports for setting out the clinical application of Ginkgolides Dropping Pills. Methods: Ten healthy subjects were enrolled in a randomized and open experimental design. Following a single oral administration of Ginkgolides Dropping Pills, blood samples which were anticoagulated by heparin sodium were collected at predetermined time, and then centrifuged to separate plasma samples. The total concentration of ginkgolide A and ginkgolide B in plasma samples and the lactone concentration of ginkgolide A and ginkgolide B were determined by a verified LC-MS/MS method, the pharmacokinetic parameters were calculated by WinNonlin 6.3 with non-compartment model. Results: After a single oral administration of Ginkgolides Dropping Pills, the tmax of lactone, total concentration of ginkgolide A respectively were (3.05 ± 1.40), (3.40 ± 1.22) h, the Cmax were (84.3 ± 32.8), (92.2 ± 35.0) ng/mL, respectively, and its Cmax ratio was 91.4%. The AUC0-t were (636 ± 183), (753 ± 205) ng∙h/mL, respectively, and its AUC0-t ratio was 84.5%, half-life time (t1/2) were (13.0 ± 10.3), (12.9 ± 8.49) h, respectively. The Tmax of lactone, total concentration of ginkgolide B were (3.15 ± 1.42), (3.35 ± 1.25) h, The Cmax were (74.1 ± 31.5), (148 ± 60.1) ng/mL, respectively, and its Cmax ratio was 50.1%.The AUC0-t were (627 ± 202), (1410 ± 431) ng∙h/mL, respectively, and its AUC0-t ratio was 44.5%, t1/2 were (13.2 ± 5.83), (13.7 ± 5.83) h, respectively. Conclusion: The results demonstrated that ginkgolide A and ginkgolide B were both at a moderate absorption and elimination rate, ginkgolide A mainly existed in human plasma upon lactone, while ginkgolide B presented as hydrolyzed forms with one or two lactone groups hydrolyzed and lactone, and the two forms of ginkgolide B were at equal exposure level after single oral administration of Ginkgolides Dropping Pills.

Evaluation of the Effect of Lentinula Edodes Mycelia Extract on Immune Function in Healthy Subjects Placebo-controlled, Parallel-group Study / 日本補完代替医療学会誌

In this study, we examined the effects of Lentinula edodes mycelia (LEM) on fatigue and immune function in healthy subjects. 22 people were randomly assigned in a 1:1 ratio to the LEM ingestion group and the placebo group. Daily oral ingestion of LEM for 4 weeks (600 mg/day) significantly improved the VAS fatigue score compared with before treatment (p<0.01). Additionally, NK cell activity was increased by ingestion of LEM (p<0.01) and was higher level compared to the placebo group (p<0.05). These results indicate that oral ingestion of LEM may improve the feeling of fatigue and immune function.

Comparison of effect of concurrent phone texting on gait speed in young and middle aged healthy subjects

Background: Around the world today, adoption of mobile media phones and its advancement have been growing at dizzying pace in all age groups. People use phone while walking on/crossing roads, climbing stairs, driving cars, etc. Using a smartphone while walking has shown decrease in walking speed and affect dynamic balance by reducing cognitive ability. The objective of study is to see and compare effect of concurrent phone texting while obstacle walking on walking time in young and middle-aged healthy subjects.Methods: An observational study with 100 healthy individuals (50 young and 50 middle-aged) were taken and had to walk on a 15 m walkway with obstacle (approximately 10% of subject’s height) at 8m distance from start without and with texting. The text messages used were all short objective questions and were sent to them approximately 2 steps prior to reaching the obstacle. Their walking time was analyzed.Results: Wilcoxon test used to analyze difference within group. In young people without phone texting it was11.41±1.24 seconds and with texting was14.79±2.67seconds, (z=-6.101, p<0.001) and in middle aged was14.93±1.20 seconds and 20.52±1.87 seconds respectively (z=-6.154, p<0.001). Mann Whitney test used to analyze difference between groups. For without texting in young and middle aged walking time (U=48.0, p<0.001), with texting young and middle aged walking time (U=122.00, p<0.001) and comparing the difference in walking time between young and middle aged with and without phone texting (U=372.5, p<0.001).Conclusions: Phone texting increases walking time in young and middle aged with difference in walking time more in middle aged adults.

Diferencia de la huella plantar (antes y después de realizar ejercicio físico) de estudiantes de primer semestre, aparentemente sanos, de la facultad de cultura física deporte y recreación de la universidad santo tomás de colombia, sede campus san alberto magno

Introducción. Durante la evaluación funcional es necesario diagnosticar la distribución de las cargas corporales de los sujetos, uno de los mecanismos más efectivos para dicha evaluación es el protocolo del fotopodograma, en el cual se evalúa la huella plantar antes y después de realizar ejercicio físico. Métodos. Se realizó el protocolo del fotopodograma a veinte y ocho estudiantes universitarios, la actividad física de intensidad moderada consistió en una carrera continua, con intensidad moderada durante 15 minutos alrededor de la pista de atletismo. Resultados. Se encontró que hubo un mayor promedio en el tipo de pie normal antes y después de hacer actividad física, así mismo se encontró cambios de la huella con la actividad física aunque estos no son estadisticamente significativos. Conclusiones. A pesar de que no hubo cambios significativos en las tomas pre y pos, sí se evidencia que esta evaluación se debe realizar después de la actividad física para reconocer con mayor precisión las cargas que se acomodan en la huella plantar.

Introduction: During functional evaluation, it is necessary to diagnose the distribution of body burden in the subjects. One of the most effective mechanisms to do so, is the protocol of photopodogram, which evaluates footprint before and after doing exercise. Method: Photopodogram protocol was carried out. Twenty-eight undergraduate students took part. The physical activity consisted of a continuous race, with a moderate intensity during 15 mins, around the running tracks. Results: It was found that there was a higher average in the type of normal cake before and after doing physical activity, likewise there were changes in the footprint with physical activity although these are not statistically significant. Conclusions: Even though no significant changes appeared in the pre and post intakes, there is an evidence that this evaluation must be carried out after the physical exercise, to detail, with much more precision, the loads that settle in the footprint.

Introdução: durante a avaliação funcional, é necessário diagnosticar a distribuição das cargas corporais dos sujeitos, um dos mecanismos mais efetivos para essa avaliação é o protocolo de fotopodograma, no qual é avaliada a impressão digital dos pés antes e depois de realizar exercício físico. Métodos: foi realizado o protocolo do fotopodograma. Participaram 28 estudantes universitários. A atividade física de intensidade moderada consistiu em uma corrida contínua, com a intensidade moderada durante 15 minutos ao redor da pista de atletismo. Resultados: verificou-se que houve uma média da população com um tipo de pé normal e, além disso, 17 sujeitos com o mesmo tipo de pé, direito e esquerdo, antes de depois de realizar exercício físico. Conclusoes: apesar de não ter havido mudanças significativas nas tomadas pré e pós-exercício físico, fica evidente que essa avaliação deve ser realizada depois deste, para reconhecer, com mais exatidão, as cargas que são acomodadas na impressão digital dos pés.

Measurement of Vessel Density Using Optical Coherence Tomography-angiography in Normal Subjects: Difference by Analysis Area

PURPOSE: To evaluate the vessel density of macula according to analysis area in health subjects using optical coherence tomography angiography (OCTA). METHODS: We retrospectively analyzed 30 eyes of 20 healthy people who underwent OCTA. We measured vessel density (VD) according to analysis area and foveal avascular zone (FAZ) size of superficial capillary plexus (SCP) and deep capillary plexus (DCP). The analysis areas were classified as 3 × 3 mm scan area (Box), Box area excluding FAZ (Box-FAZ), fovea centered 3 mm circle area (Circle), Circle area excluding FAZ (Circle-FAZ) and area between fovea centered 1 mm circle and 3 mm circle (Ring). RESULTS: The SCP VDs were Box 34.00 ± 3.97, Box-FAZ 35.37 ± 4.09, Circle 31.70 ± 4.56, Circle-FAZ 33.34 ± 4.72, and Ring 35.22 ± 5.09. The DCP VDs were Box 30.04 ± 3.51, Circle 29.49 ± 3.57, Box-FAZ 31.59 ± 3.65, Circle-FAZ 31.46 ± 3.72, and Ring 32.60 ± 4.00. There was a significant difference according to analysis area from both SCP and DCP (p < 0.001 and p < 0.001, respectively). Comparison of the vessel density between SCP and DCP in the same analysis area were different in all areas (p < 0.001, p = 0.001, p < 0.001, p = 0.005, p = 0.001, respectively). CONCLUSIONS: This study shows different results according to analysis area when measuring VD using OCTA. Therefore, when comparing studies related to VD, it is necessary to pay attention to the analysis area in the interpretation of the results.

Prevalence of Toxoplasma gondii Infection in Hemodialysis Patients with Chronic Renal Failure and Risk Factors in Diyala Province, Iraq

@#Introduction: Toxoplasma gondii is a protozoan parasite which causes a zoonotic disease called toxoplasmosis. The main purpose of this study was to investigate the seropositivity rate of specific antibodies “anti-T. gondii IgG and IgM antibodies using enzyme-linked immunosorbant assay” in hemodialysis patients attending the Teaching Hospital, Baquba City, Diyala Province, Iraq and to determine the potentially preventable risk factors. Methods: Eighty five hemodialysis patients with kidney failure and 85 healthy volunteers were selected for this study. Results: The percentage of seropositivity for IgG antibodies in patients with hemodialysis was 54.1% while it was 38.2% among the healthy control subjects and the difference was significant between the two groups [Odds Ratio (OR)= 1.8586; 95% Confidence Interval (CI)= 1.0097-3.4212; P= 0.0465]. In contrast, IgM antibodies were not detected in any of the patients or the healthy subjects. Many risk factors were identified, including contact with cats (OR, 2.62; P= 0.0398); eating undercooked meat (OR, 2.6, P= 0.0439); drinking unfiltered water (OR, 2.86, P= 0.0433); and eating outside the home (OR, 5.6, P= 0.0024) as risk factors for toxoplasmosis. However, smoking was not found to be as a risk factor for toxoplasmosis (OR, 2.1, P= 0.1204). Conclusion: The results of the present study revealed a high prevalence of toxoplasma infection in hemodialysis patients and therefore, we recommend monitoring these patients for T. gondii infection to minimize the spreading of toxoplasmosis via treating the seropositive patients with the available commercial drugs.

Effect of Phacoemulsification on Intraocular Pressure in Healthy Subjects and Glaucoma Patients

BACKGROUND: We investigated how cataract surgery might influence long-term intraocular pressure (IOP) change in both healthy subjects and glaucoma patients. METHODS: A retrospective analysis of patients who had had clear corneal phacoemulsification with a minimum of 12 months of follow up was performed. Glaucoma patients with medically controlled open-angle glaucoma and healthy subjects with no glaucoma were included in the analysis. The change of IOP after phacoemulsification and factors associated with postoperative IOP change were investigated. RESULTS: In total, 754 eyes of 754 patients, specifically 106 patients with glaucoma and 648 patients with no glaucoma (i.e., healthy subjects) were enrolled. The phacoemulsification effected a reduction of IOP: 1.03 ± 3.72 mmHg in healthy subjects and 1.08 ± 3.79 mmHg in glaucoma patients at postoperative 1 year (P = 0.656). There were negative coefficients of IOP until 1 year of follow up (all P < 0.001), but the IOP change gradually showed a less steeply decreasing slope (correlation coefficient: −0.993), compared with those for 1 week and 1 month of follow up (correlation coefficients: −1.893 and −1.540, respectively). In the multivariate analysis, age and preoperative IOP showed significant associations with postoperative IOP change (regression coefficients: −0.034 and 0.419 respectively, all P < 0.001). CONCLUSION: Phacoemulsification resulted in IOP reduction, which effect regressed in healthy subjects and glaucoma patients over the course of long-term follow up. Therefore, long-term monitoring of IOP change is needed. In cases of higher preoperative IOP and young patients, phacoemulsification alone is a reliable option for IOP control.

Analysis of Foveal Microvascular Structures Using Optical Coherence Tomography Angiography in Age-stratified Healthy Koreans

PURPOSE: To evaluate foveal avascular zone (FAZ) microvascular structural changes in healthy Korean subjects stratified by age using optical coherence tomography angiography (OCTA). METHODS: Eighty eyes of 43 healthy volunteer subjects who had 20/20 or better best corrected visual acuity without other ocular or systemic disease except vitreous floaters and dry eye syndrome were enrolled and stratified by age group. To measure FAZ size and vascular density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), OCTA (DRI OCT Triton, Swept Source OCT, Topcon, Tokyo, Japan) scans were performed over fovea-centered 3 × 3 mm² regions, and then compared with central macular thickness (CMT) and subfoveal choroidal thickness. RESULTS: Mean age of the participants was 46.4 ± 16.1 (20–78). The SCP and DCP FAZ sizes were 0.32 ± 0.11 mm² and 0.41 ± 0.14 mm², respectively. There was a significant difference by age group (p < 0.001, p < 0.001), respectively. The FAZ VD for SCP and DCP was 28.96 ± 3.05% and 33.15 ± 3.64%, respectively. There was no difference between age groups (p = 0.118, p = 0.637). Univariate and multiple linear regression analysis showed that the FAZ size of SCP and DCP was significantly correlated with age (p = 0.039, p = 0.002) and CMT (p = 0.007, p = 0.013), respectively. The SCP and DCP FAZ size were positively correlated with age (R² = 0.279, p < 0.001, R² = 0.344, p < 0.001), and negatively correlated with CMT (R2 = 0.354, p < 0.001, R2 = 0.285, p < 0.001), respectively. CONCLUSIONS: The FAZ size of SCP and DCP increased with age and were negatively correlated with CMT. These results suggest that consideration of age and CMT is important when performing the clinical evaluation of FAZ size in healthy subjects.

Estudio de patrones capilaroscópicos en población sana / Capillarroscopic patterns in healthy population

La capilaroscopia es un método no invasivo y seguro que permite la visualización de los capilares a nivel del lecho periungueal de los dedos de las manos. Es útil en la evaluación del Fenómeno de Raynaud y de las colagenopatías, principalmente de la esclerodermia; sin embargo, se conoce poco acerca de la prevalencia y distribución de los cambios capilaroscópicos en sujetos sanos, siendo el objetivo de este estudio evaluar y describir las alteraciones capilaroscópicas en este grupo. A 100 participantes seleccionados por criterios de inclusión y exclusión se les realizó una videocapilaroscopia del lecho ungueal del cuarto y quinto dedo de la mano no dominante; el 86% de la población estudiada presentó hallazgos capilaroscópicos como: capilares tortuosos, entrecruzados y arborificados. Además, las alteraciones capilaroscópicas fueron más frecuentes en sujetos que consumían tabaco, se encontró una relación significativa entre el tabaco y la presencia de arborificaciones. Este es el primer estudio descriptivo de alteraciones capilaroscópicas en sujetos sanos en el Ecuador.

Capillaroscopy is a noninvasive and safe method that allows visualizationof capillaries in the nailbed. It is useful in the assesment ofRaynaud’s phenomenon and collagen diseases, especially scleroderma;however, little is known about the prevalence and distributionof capillaroscopic changes in healthy subjects, hence the aim ofthis study was to assess and describe the microvascular alterationsin this group. 100 participants selected by inclusion and exclusioncriteria underwent videocapillaroscopy of the nailfold of the fourthand fifth fingers of the nondominant hand; 86% of the study populationpresented capillaroscopic findings such as tortuous capillaries,crisscrossing and arborifications. Also, the microvascular alterationswere more frequent in subjects who had history of tobaccosmoking: a significant relationship between smoking and the presenceof arborifications was found. This is the first descriptive studyof microvascular alterations in healthy subjects in Ecuador.

Population Pharmacokinetics of Midazolam in Healthy Koreans: Effect of Cytochrome P450 3A-mediated Drug-drug Interaction

OBJECTIVE: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. METHODS: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model (NONMEM® 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. RESULTS: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. CONCLUSION: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.

The acute effect of maximal exercise on plasma beta-endorphin levels in fibromyalgia patients

BACKGROUND: This study aimed to investigate the effect of strenuous exercise on β-endorphine (β-END) level in fibromyalgia (FM) patients compared to healthy subjects. METHODS: We enrolled 30 FM patients and 15 healthy individuals. All study participants underwent a treadmill exercise test using modified Bruce protocol (M.Bruce). The goal of the test was achieving at least 70% of the predicted maximal heart rate (HRMax). The serum levels of β-END were measured before and after the exercise program. Measurements were done while heart rate was at least 70% of its predicted maximum. RESULTS: The mean ± the standard deviation (SD) of exercise duration in the FM and control groups were 24.26 ± 5.29 and 29.06 ± 3.26 minutes, respectively, indicating a shorter time to achieve the goal heart rate in FM patients (P < 0.003). Most FM patients attained 70% HRMax at lower stages (stage 2 and 3) of M.Bruce compared to the control group (70% versus 6.6%, respectively; P < 0.0001). Compared to healthy subjects, FM patients had lower serum β-END levels both in baseline and post-exercise status (Mean ± SD: 122.07 ± 28.56 µg/ml and 246.55 ± 29.57 µg/ml in the control group versus 90.12 ± 20.91 µg/ml and 179.80 ± 28.57 µg/ml in FM patients, respectively; P < 0.001). CONCLUSIONS: We found that FM patients had lower levels of β-END in both basal and post-exercise status. Exercise increased serum the β-END level in both groups but the average increase in β-END in FM patients was significantly lower than in the control group.

The acute effect of maximal exercise on plasma beta-endorphin levels in fibromyalgia patients

BACKGROUND: This study aimed to investigate the effect of strenuous exercise on β-endorphine (β-END) level in fibromyalgia (FM) patients compared to healthy subjects. METHODS: We enrolled 30 FM patients and 15 healthy individuals. All study participants underwent a treadmill exercise test using modified Bruce protocol (M.Bruce). The goal of the test was achieving at least 70% of the predicted maximal heart rate (HRMax). The serum levels of β-END were measured before and after the exercise program. Measurements were done while heart rate was at least 70% of its predicted maximum. RESULTS: The mean ± the standard deviation (SD) of exercise duration in the FM and control groups were 24.26 ± 5.29 and 29.06 ± 3.26 minutes, respectively, indicating a shorter time to achieve the goal heart rate in FM patients (P < 0.003). Most FM patients attained 70% HRMax at lower stages (stage 2 and 3) of M.Bruce compared to the control group (70% versus 6.6%, respectively; P < 0.0001). Compared to healthy subjects, FM patients had lower serum β-END levels both in baseline and post-exercise status (Mean ± SD: 122.07 ± 28.56 µg/ml and 246.55 ± 29.57 µg/ml in the control group versus 90.12 ± 20.91 µg/ml and 179.80 ± 28.57 µg/ml in FM patients, respectively; P < 0.001). CONCLUSIONS: We found that FM patients had lower levels of β-END in both basal and post-exercise status. Exercise increased serum the β-END level in both groups but the average increase in β-END in FM patients was significantly lower than in the control group.

The ACE I/D polymorphism is associated with nitric oxide metabolite and blood pressure levels in healthy Mexican men / El polimorfismo I/D de la ECA se asocia con los niveles de metabolitos óxido nítrico y de presión arterial en hombres mexicanos sanos

The I/D insertion/deletion polymorphism of the angiotensin-converting enzyme has been related to hypertension. This polymorphism also seems to have gender related implications. Angiotensin II contributes to the production and release of oxygen reactive species that react with nitric oxide, inactivating its effects. Objective: To establish whether the ACE I/D polymorphism correlates with nitric oxide plasma metabolites in healthy men and women. Methods: Among 896 subjects between 18 and 30 years of age range, 138 fulfilled inclusion criteria. The polymorphism was identified by polymerase chain reaction, and blood nitric oxide metabolites were analyzed following the method described by Bryan. Results: Both systolic and diastolic arterial pressures were higher in men than in women (107/67 vs. 101/65 mmHg, p < 0.001). In terms of the ACE gene, there were differences in the concentration of nitric oxide metabolites in men with the I/D and D/D genotypes when compared to carriers of the I/I genotype (33.55 and 29.23 vs. 53.74 pmol/ml; p = <0.05), while there were no significant differences in women when compared by genotype. Men with the D/D genotype had higher systolic blood pressure than I/D carriers (111 vs. 104 mmHg, p < 0.05). We observed no arterial blood pressure differences in women when grouped by ACE genotype. Conclusions: The ACE D/D genotype was associated with nitric oxide metabolite levels and systolic blood pressure in clinically healthy men while it had no effect in women.

El polimorfismo inserción/deleción del gen de la enzima convertidora de la angiotensina (polimorfismo I/D de la ECA), se relaciona con hipertensión y sus efectos podrían estar asociados al género. La angiotensina II contribuye a la producción y liberación de especies reactivas de oxígeno, que reaccionan con el óxido nítrico (ON), inactivándolo. Objetivo: Conocer si existen diferencias en la concentración de metabolitos de ON en hombres y mujeres sanos que puedan estar influidas por el polimorfismo I/D de la ECA. Métodos: De 896 sujetos de entre 18 y 30 años, 138 cumplieron los criterios de inclusión. El polimorfismo fue identificado usando reacción en cadena de la polimerasa y los metabolitos de ON fueron analizados en sangre usando el método de Bryan. Resultados: Las presiones sistólica y diastólica fueron más elevadas en hombres que en mujeres (107/67 vs. 101/65 mmHg p < 0.001). En relación con el genotipo, existieron diferencias significativas en la concentración de metabolitos de ON en los hombres con genotipos I/D, D/D comparados con los portadores del genotipo I/I (33.55 y 29.23 vs. 53.74 pmol/ml, respectivamente; p = <0.05). No hubo diferencias significativas en las mujeres portadoras de los diferentes genotipos. Respecto a la presión arterial, los hombres con genotipo D/D presentaron mayor presión arterial sistólica que aquellos portadores de I/D (111 vs. 104 mmHg, p < 0.05). En las mujeres no se observaron diferencias significativas comparándolas por genotipo. Conclusiones: El genotipo D/D de la ECA está asociado con el nivel de metabolitos de ON en plasma y la presión arterial sistólica en hombres clínicamente sanos; esta asociación no se observa en las mujeres.

Seroprevalence of Hepatitis G Virus IgG Antibody among Blood Donors, Pregnant Women, Neonates and Apparently Healthy Population.

This cross sectional and observational study was conducted in the Department of Microbiology, Sylhet MAG Osmani Medical College, Sylhet, during the period from 1st January 2012 to 31st December 2012 with a view to explore the seropositivity of Hepatitis G virus (HGV) in blood donors, pregnant women, new born and apparently healthy subjects. For this purpose 45 blood donors, 45 pregnant women, 45 new born babies of same mothers and 45 apparently healthy subjects were selected according to the inclusion and exclusion criteria. The HGV antibody was measured in venous blood from blood donor, pregnant women and apparently healthy subjects; and cord blood from newborn babies with a commercially available enzyme-linked immunosorbent assay (ELISA) method. The mean age of the blood donors, pregnant women and healthy subjects was 24.9 (SD ± 3.5) years; 24.9 (SD ± 3.5) years and 22.1 (SD ± 1.5) years respectively. The overall seropositivity of HGV was 3 (1.7%). The seropostivity of HGV of blood donors, new born babies and healthy subjects was 1 (2.2%) in each group but no HGV antibody positivity among the pregnant women (p=0.797). Among the male patients 2 (2.2%) patients were seropositive for HGV; while in female patients, 1 (1.1%) patient was seropositive for HGV (p=0.547). Among the patients with previous blood transfusion 1 (1.9%) patient was seropositive for HGV; while among patients without previous blood transfusion 2 (1.6%) patients were seropositive for HGV (p=0.882). This study yielded that there is high prevalence of HGV seropositivity among population in this region of Bangladesh. So, screening of blood units for HGV would deserve consideration.

Comparison of the Population Pharmacokinetics and Safety Between Please Orally Soluble Film and VIAGRA(R) in Healthy Male Volunteers

BACKGROUND: The objective of this study was to compare the pharmacokinetics and safety between newly developed sildenafil (Please Orally Soluble Film) and sildenafil citrate (VIAGRA(R)) after single oral administration in healthy Korean male subjects. METHODS: A randomized, open-label, single dose, 2-way crossover study was conducted in 50 healthy male subjects. Each sequence group consisted of 25 subjects, received a single oral 50 mg dose of Please Orally Soluble Film (test formulation) or VIAGRA(R) (reference formulation) by study period. Blood samples were obtained during a 24-hour period after dosing. Sildenafil and its metabolite concentrations were determined using validated LC-MS/MS. A non-compartmental pharmacokinetic analysis was performed. Safety was assessed through monitoring of adverse events, vital sign check-up, physical examination, laboratory tests and electrocardiography. RESULTS: All enrolled participants completed the study. The point estimates and 90% confidence intervals of log transformed C(max) and AUC(last) of the test formulation in comparison to those of reference formulation were 0.9294(0.8353 - 1.0341) and 0.9415 (0.8869 - 0.9994) respectively. The analysis of variance showed no significant influences of formulation, sequence and period on the pharmacokinetic parameters. The frequencies of adverse events were not statistically different between the formulations. No serious adverse event was observed or reported. CONCLUSION: Please Orally Soluble Film could be considered bioequivalent to VIAGRA(R) and had similar safety properties in healthy Korean male subjects.

Pharmacokinetic Characteristics of Cefcapene Pivoxil Hydrochloride after Single Oral Administration in Healthy Korean Subjects

BACKGROUND: Cefcapene pivoxil hydrochloride (CFPN-PI) is an oral ester cephalosporin antibiotic with a broad spectrum. In this study, we investigated the pharmacokinetics (PK) and tolerability of CFPN-PI following single oral administration in healthy Korean subjects. METHODS: An open label, dose escalation, parallel group study was conducted in 18 healthy male volunteers. A single dose of CFPN-PI was administered to 6 subjects in each treatment group of 100, 150 and 200 mg. Serial blood and urine samples were collected up to 12 h and 24 h after dosing, respectively. Plasma and urine concentrations of cefcapene were measured by HPLC-UV. PK parameters were estimated using non-compartmental analysis. For the safety evaluation, adverse event monitoring, clinical laboratory tests and physical examination were performed throughout the study. RESULTS: Median values of time to peak plasma concentration were observed around 1.5 to 2.0 h. Maximum plasma concentrations (Cmax) were 1.04 +/- 0.22, 1.24 +/- 0.46 and 1.56 +/- 0.43 mg/L (mean +/- SD), and area under the plasma concentration time curve (AUCinf) were 2.94 +/- 0.46, 3.97 +/- 1.28 and 4.70 +/- 1.19 h*mg/L in 100, 150 and 200 mg dose groups, respectively. The differences of dose normalized Cmax and AUCinf among three groups were not statistically significant. The fractions of drug excreted in urine unchanged were 31.5 % - 42.9 %. There were no serious adverse events or clinically significant abnormalities related to CFPN-PI. CONCLUSION: CFPN-PI was well tolerated with single oral administration and showed a linear PK property within 100 - 200 mg in healthy Korean male subjects.

Renal oxygen content is increased in healthy subjects after angiotensin-converting enzyme inhibition

OBJECTIVE: The association between renal hypoxia and the development of renal injury is well established. However, no adequate method currently exists to non-invasively measure functional changes in renal oxygenation in normal and injured patients. METHOD: R2* quantification was performed using renal blood oxygen level-dependent properties. Five healthy normotensive women (50±5.3 years) underwent magnetic resonance imaging in a 1.5T Signa Excite HDx scanner (GE Healthcare, Waukesha, WI). A multiple fast gradient-echo sequence was used to acquire R2*/T2* images (sixteen echoes from 2.1 ms/slice to 49.6 ms/slice in a single breath hold per location). The images were post-processed to generate R2* maps for quantification. Data were recorded before and at 30 minutes after the oral administration of an angiotensin II-converting enzyme inhibitor (captopril, 25 mg). The results were compared using an ANOVA for repeated measurements (mean + standard deviation) followed by the Tukey test. ClinicalTrials.gov: NCT01545479. RESULTS: A significant difference (p<0.001) in renal oxygenation (R2*) was observed in the cortex and medulla before and after captopril administration: right kidney, cortex = 11.08 ± 0.56ms, medulla = 17.21 ± 1.47ms and cortex = 10.30 ± 0.44ms, medulla = 16.06 ± 1.74ms, respectively; and left kidney, cortex= 11.79 ± 1.85ms, medulla = 17.03 ± 0.88ms and cortex = 10.89 ± 0.91ms, medulla = 16.43 ± 1.49ms, respectively. CONCLUSIONS: This result suggests that the technique efficiently measured alterations in renal blood oxygenation after angiotensin II-converting enzyme inhibition and that it may provide a new strategy for identifying the early stages of renal disease and perhaps new therapeutic targets.

Inmunopatología de sujetos sanos de un área endémica para pénfigo foliáceo en Perú: Estudio comparativo con familiares / Immunopathologic characterization of healthy subjects in an endemic area for pemphigus foliaceus: Comparative study with relatives.

Introducción: el pénfigo foliáceo endémico (PFE) ha sido descrito a principios de los años 50 en la selva peruana. En el 2006, Ortega y col. reportaron la presencia de anticuerpos anti-desmogleina 1 en Pueblo Libre, Ucayali. Sin embargo, no existen reportes inmunológicos sobre los familiares de pacientes con PFE en la zona. Objetivos: comparar las características inmunopatológicas de los sujetos sanos de Pueblo Libre (Campo Verde-Ucayali) endémico para pénfigo foliáceo, con familiares sanos de pacientes con PFE y controles sanos de áreas no endémicas. Material y métodos: estudio prospectivo y multicéntrico realizado de junio a agosto del 2006 que incluyó a 41 sujetos sanos de la comunidad de Pueblo Libre, 11 familiares de pacientes con PFE y 20 sujetos sanos de áreas no endémicas de la enfermedad de los que se obtuvo muestras de sangre para la realización del estudio inmunopatológico (ELISA para anticuerpos anti desmogleína 1 y anti desmogleína 3) comparándose las características de cada grupo de investigación. Para fijar los valores de corte se realizó la estandarización del ELISA usando el análisis de características operativas del receptor (ROC). Resultados: en Pueblo Libre se encontró una prevalencia de anticuerpos anti desmogleína 1 de 46,3%. El patrón predominante fue el IgG2 (62,5%) y el IgG1 (56,3%). En el 31,7% se detectó anticuerpos anti-desmogleína 3. Existió alta correlación entre los valores índice de anticuerpos anti desmogleína 1 y anti desmogleína 3 (r=0,76), significativa a un nivel α=0,01. Para los familiares de los pacientes con PFE, el 45,5% fueron positivos para anticuerpos anti-desmogleνna 1 con un patrσn predominante IgG1 (63,6%) e IgG2 (54,5%). Se detectó anticuerpos anti-desmogleína 1 en el 10 % de sujetos sanos de áreas no endémicas; no se detectó anticuerpos anti desmogleína 3 en este grupo. Conclusiones: las personas sanas expuestas a factores ambientales de los focos endémicos de PFE y los familiares de pacientes desarrollan anticuerpos no patogénicos anti desmogleína 1 y 3 con características inmunopatológicas similares.

Introduction: endemic pemphigus foliaceus (PFE) has been described at the beginning of the 50s in the peruvian forest. In 2006,Ortega & col. reported the presence of desmoglein 1 antibodies in Pueblo Libre, Ucayali. Nevertheless, immune reports does not exist on patients’ relatives with PFE in the zone. Objetives: to compare the immunopathologic profiles of healthy subjects from Pueblo Libre (an area in Ucayali, endemic for pemphigus foliaceus), with healthy relatives of patients with endemic pemphigus foliaceus (EPF) and healthy controls from non-endemic areas. Materials and methods: this is a prospective multicentric study performed from June to August 2006. The sample consisted of 41 healthy subjects from the Pueblo Libre community, 11 relatives of EPF patients and 20 healthy subjects from non-endemic areas. Blood samples were obtained for immunopathologic studies (ELISA technique for antibodies against desmoglein-1 and desmoglein- 3). The immunopathologic profiles of each group were compared. Standardization of ELISA was performed using the analysis of receptor operative characteristics (ROC) to find appropriate cut-off values. Results: in Pueblo Libre, the prevalence of antibodies against desmoglein-1 was 46,3%. The predominant pattern was 56,3% for IgG1 and 62,5% for IgG2. Antibodies against desmoglein-3 were found in 31,7% of the sample. A high correlation was found between the index values of antibodies against desmoglein-1 and desmoglein-3. (r=0.76); this is statistically significant, with an alpha = 0,001. The frequency of antibodies against desmoglein-1 was 45,5% in the relatives of EPF patients; the predominant pattern was 63,6% for IgG1 and 54,5% for IgG2. Antibodies against desmoglein-1 were detected in two healthy subjects from non-endemic areas; antibodies against desmoglein-3 were not detected. Conclusion: healthy subjects who are exposed to environmental factors in a focus of endemic pemphigus foliaceus and the relatives of patients with EPF develop non-pathogenic antibodies against desmoglein-1 and -3 with similar immunologic profiles.

Diagnostic Approach to Abnormal Liver Tests in Apparently Healthy Subjects

Blood tests such as aminotransferases are indicators of liver cell injury not liver function, so it would be more appropriate to call them liver tests instead of liver function tests. Liver tests should be interpreted in a clinical context, and follow-up tests are often helpful to assess liver diseases. Abnormal liver tests in apparently healthy individuals can be categorized into four types: (1) isolated elevation of serum bilirubin; (2) isolated elevation of serum alkaline phosphatase (ALP); (3) hepatocellular injury; and (4) intrahepatic cholestasis. Mild unconjugated hyperbilirubinemia without any other test results is frequently suggestive of Gilbert syndrome, which needs no specific therapy, but the possibility of hemolysis should be ruled out. An isolated elevation of ALP can be due to non-hepatic causes such as normal rapid growth, pregnancy, or bone diseases. The source of the elevated ALP can be considered to be of hepatic origin if gamma-glutamyl transpeptidase (GGT) increases simultaneously. GGT also increases after chronic ethanol ingestion. A significant elevation of ALP also occurs in infiltrative lesions of lymphoma or leukemia. Up to 25% of asymptomatic testees show a mild elevation of aminotransferases. A substantial proportion of them have parenchymal liver diseases such as fatty liver, chronic hepatitis, or early cirrhosis. A history of exposure to hepatotoxins, physical examination, and tests for viral markers are helpful. If ALT is normal, the increased AST is highly likely to be of muscle origin. Serum ALP and GGT increase mainly in intrahepatic cholestasis, and early stage of primary biliary cirrhosis or drug-induced cholestasis should be considered.