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Background: Pain has an adverse effect on HRQoL and has social, psychological, and physical repercussions for ESRD patients. In the present study, we assessed chronic pain in ESRD patients on HD in terms of severity and interference with activity. We also assessed the impact it has on these patients, along with looking at the factors that were linked to QoL in this population., Methods: A multicenter, cross-sectional study carried out between April and July of 2023 in the hemodialysis units of Asir Central Hospital and Khamis Mushait General Hospital. Brief Pain Inventory and European Quality of Life scale 5 dimensions (EQ-5D) scale, including its European Quality of Life visual analogue scale (EQ-VAS) component, were used to assess pain and QoL, respectively., Results: A total of 97 participants were included in the final study. The average interference level of pain with daily functions was 22.5 ± 15.0 out of 70. The mean interference score was significantly higher among patients at rural areas (28.2 ± 16.3; P = 0.012), and those who undergone dialysis session for ≥ 4 times per week (31.6 ± 16.7; P = 0.026). The overall score of quality of life ranged from 20% to 92% with mean score of 36.5 ± 12.8%. The multiple linear regression analysis revealed that patients with higher BMI, more frequent dialysis sessions per week, and higher level of pain interference with daily functions demonstrated lower QoL (B= - 2.36, - 1.46, and - 0.64, respectively., Conclusions: Pain has a significant negative impact on QoL in ESRD patients undergoing HD. Patients with higher BMI, more frequent dialysis sessions, and higher level of pain interference with daily functions are at higher risk of lower QoL. These findings provide valuable information for educators, physicians, and other healthcare providers working with patients undergoing HD., Competing Interests: Declaration of Competing Interest The authors stated no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: During the COVID-19 pandemic, there was increased adoption of telepharmacy, which has proven benefits. This study was conducted to assess the knowledge and perception of the community pharmacists of Aseer region, Saudi Arabia, towards telepharmacy services and evaluate their willingness to adopt telepharmacy in clinical practice during the COVID-19 pandemic., Materials and Methods: A cross-sectional study was conducted using an online self-administered structured anonymous questionnaire on the community pharmacists of Aseer region, Saudi Arabia. It covers demographics, computer access and literacy, knowledge and perception, and willingness to practice telepharmacy. Results were expressed as frequencies, percentages, and mean. The comparison between the classes of the demographic variables and the scores was done via Kruskal-Wallis and Mann-Whitney tests., Result: About half of the pharmacists in our study showed average knowledge about telepharmacy, the practical application of telepharmacy technology, and telepharmacy guidelines with a percentage of 53%, 52%, and 47%, respectively). Majority of the participants showed high perception towards telepharmacy in Saudi Arabia, while 93% of the pharmacists in Saudi Arabia agreed that the implementation of telepharmacy technology is appropriate due to the current COVID-19 pandemic. Only a significant relation was found between gender and computer access, literacy, and perceptions towards telepharmacy with p values of 0.033 and 0.026, respectively., Conclusion: The majority of the community pharmacists exhibited a positive perception and are willing to practice the concept of telepharmacy despite having a below average knowledge of telepharmacy. A future study involving the entire kingdom of Saudi Arabia could help identify the gaps in the knowledge, perception, and willingness to practice telepharmacy on a broader scale and thus promote telepharmacy adoption in the entire kingdom., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Ayesha Siddiqua et al.)

Objective: Even before the outbreak of the COVID-19 pandemic, concerns regarding college students' mental health were on the rise due to the increasing number of students afflicted with mental health issues. Exposure to numerous pandemic-related measures exacerbated existing issues with anxiety, depression, and stress. This study aimed to assess depression, anxiety, and stress levels among university students in the Aseer region in Saudi Arabia., Subjects and Methods: Data were collected from eligible individuals using a web-based, self-administered DASS-21 questionnaire. This questionnaire consists of 21 questions with a rating scale of 0-3. Each of the psychological factors of depression, anxiety, and stress was categorized as normal, mild, moderate, severe, and extremely severe. Results were expressed using descriptive statistics as proportions, and the Mann-Whitney/Kruskal-Wallis' test was used to evaluate the presence of a significant difference between each of the socio-demographic factors of the respondents and the psychological outcomes., Results: Respondents aged between 18-24 years reported higher rates of extremely severe depression than other age groups. Females had higher rates of depression, especially severe and extremely severe forms. Extremely severe anxiety had a relatively high prevalence across all age groups. Extremely severe stress was more common among respondents aged between 18-24 years, while respondents older than 34 years reported the highest prevalence of severe stress. The Mann-Whitney/Kruskal-Wallis' tests showed statistically significant differences between participants in the different groups., Conclusions: The COVID-19 pandemic had a high psychological impact on university students, which indicates that a psychological support program should be implemented to reduce this impact.

Objective: This study aimed to estimate how prevalent potential drug-drug interactions (pDDIs) were in patients with cardiovascular diseases who were hospitalized for more than 24 hours, and to determine the risk factors associated with these pDDIs., Patients and Methods: A prospective observational study was conducted on patients admitted to the cardiac care unit in a tertiary care hospital. We included two hundred medical records of cardiovascular disease patients who were prescribed more than one drug. These medical records were analyzed for pDDIs using the Micromedex drug interaction checker database. Data were analyzed using Descriptive statistics. Chi-square test and the Pearson correlation coefficient were applied., Results: PDDIs were prevalent in 95% of the analyzed medical records, with at least one detected pDDI per record. Within the 200 medical records, 430 potentially interacting drug pairs were identified, with the majority resulting in moderate and major interactions. Aspirin/clopidogrel (111), furosemide/aspirin (89), enoxaparin/clopidogrel (89) and Lisinopril/aspirin (60) were the most common interacting pairs. Whereas, aspirin, heparin, clopidogrel, furosemide, ranitidine and Lisinopril were the most frequently implicated drugs in DDIs., Conclusions: PDDIs were common among hospitalized cardiovascular patients. PDDIs were associated with age and number of drugs prescribed. The routine integration of an online drug interactions screening tool may improve the ability of pharmacists to identify cardiac patients at higher risk of potential drug interactions and conduct appropriate interventions thereafter.

Background: As vaccination is a cornerstone strategy to prevent the spread of COVID-19, this study assessed and compared beliefs about and barriers to COVID-19 vaccination among the population of three countries with different Human Development Index (HDI) scores: Saudi Arabia (very high), India (medium), and Sudan (low)., Methods: A web-based, self-administered structured questionnaire was employed to collect data from the three countries. The questionnaire contained three sections that measured sociodemographic characteristics, participants' beliefs about and attitudes toward COVID-19 vaccines, barriers to receiving COVID-19 vaccines, and scenarios in which there is a possibility to take a COVID-19 vaccine. Multinomial logistic regression was used to determine whether there was an association between the country of the participant and their beliefs about COVID-19 vaccines., Results: 972 responses were collected. The study participants from India were more likely to believe in the safety and efficacy of vaccines than those from Saudi Arabia or Sudan. Consequently, they reported more willingness to get vaccinated to avoid complications from COVID-19. Regarding barriers to COVID-19 vaccination, concerns about adverse effects and ineffectiveness of vaccines were more common among Saudi participants, while concerns about conspiracy were more common among Sudanese participants., Conclusion: COVID-19 vaccine acceptance was higher in countries with a very high to medium Human Development Index, indicating greater belief in the safety and efficacy of COVID-19 vaccines., Competing Interests: The authors declare no conflicts of interest in this work., (© 2022 Makki et al.)

Background: Child labor is exploitative and harmful and deprives children of opportunities for a healthy life. Nonetheless, child labor is prevalent worldwide. Abusive working conditions are common, especially in developing countries., Objective: This study was designed both to measure the prevalence of abuse in work environments and to identify possible risk and protective factors for such abuse in child laborers in Tehran, Iran., Method: The researchers conducted this cross-sectional study from September 2018 to May 2019 in Tehran and recruited 250 children from seven child labor support centers., Results: The results demonstrated a relatively high rate of abuses experienced in work environments among Iranian child laborers: 77.6 % of children experienced at least one type of abuse, with emotional abuse (70.4 %) as the most frequently experienced abuse followed by neglect (52 %), physical abuse (5.8 %), and sexual abuse (3.6 %). Furthermore, living alone or with a single parent (OR = 3.15, CI 95 %: 1.33-7.45) was a risk factor, while working in home jobs (OR = 2.08, CI 95 %: 1.19-3.63), being male (OR = 0.19, CI 95 %: 0.06-0.55), and being older (OR = 0.32, CI 95 %: 0.17-0.60) were the protective factors of abuses experienced at work among child laborers., Conclusion: The findings of this study have implications for designing and implementing early interventions to provide less harmful work environments for child laborers. Further, advocacy efforts to prevent and eliminate child labor should be pursued., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Coexistence of spondyloarthritis (SpA) and Takayasu's arteritis is not a common finding, but such cases have been discussed, particularly in the context of choice of therapy. Inhibition of inflammation by tumor necrosis factor inhibitors (TNFi) is a key aspect of the treatment of SpA and also positive effects of such treatment in concomitant large vessel vasculitis have been reported. However, TNFi is also associated with the possibility of initiating vasculitis. The present article based on a case study and the available literature is an attempt to discuss coexistence of these two diseases and the impact of treatment with biological drugs from the anti-TNF group in the course of SpA with Takayasu's arteritis., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie.)

Background: Community adherence to current control measures is one of the vital factors that determines the success of controlling the spread of COVID-19. This adherence depends on the knowledge and attitude of a community toward COVID-19 and their precautionary measures against the disease., Objective: This study aims to evaluate the knowledge and attitude of the community from the Aseer Region, Saudi Arabia, toward COVID-19 and their precautionary measures against the disease., Methods: The descriptive cross-sectional study involved an online sample of participants from the Aseer Region, Saudi Arabia, who were recruited based on a nonprobability convenience sampling method from April to May 2020. The self-administered online questionnaire comprised four parts: the first included the demographic details of the participants; the second consisted of 11 closed-ended questions that assessed the participants' knowledge of COVID-19; the third contained six closed-ended questions that assessed the participants' overall attitude toward COVID-19; and the fourth comprised six closed-ended questions on the participants' precautionary measures against COVID-19. The data were analyzed using Statistisoftware SPSS 21.0., Results: Altogether, 740 participants completed the online questionnaire. The mean knowledge score concerning COVID-19 was 8.08 ± 1.765. Graduate participants scored significantly higher for all knowledge items than those from other educational levels. Furthermore, the main source of COVID-19 information was the Ministry of Health website 661 (89.3%). The mean attitude score regarding COVID-19 was 9.74 ± 1.935, whereas the mean precautionary measures score was 10.09 ± 1.91. University-educated participants scored significantly higher for all knowledge items than those from other educational levels. Female participants had significantly higher precautionary measures scores than male participants., Conclusion: This study confirms that residents of the Aseer Region have high knowledge of, demonstrate a positive attitude toward, and use appropriate precautionary measures against COVID-19, which is associated with obtaining information about the virus from the Ministry of Health website., Competing Interests: The authors declare no conflicts of interest for this work., (© 2020 Khaled et al.)

In England and Wales, meningococcal disease caused by group W has historically been associated with outbreaks of disease among travellers to high-risk countries. Following a large outbreak associated with travel to the Hajj in 2000, the number of cases declined and, in 2008, only 19 laboratory-confirmed cases were identified nationally. In 2013, in the East Midlands region of England, eight cases of meningococcal disease caused by this serogroup were recorded, compared with six from 2011 to 2012. To explore this further, data for all cases with a date of onset between 1 January 2011 and 31 December 2013 were collected. Data collected included geographical location, clinical presentation and outcome. Fourteen cases were identified; two died as a result of their illness and two developed long-term health problems. No commonality in terms of geographical location, shared space or activities was identified, suggesting that group W is circulating endemically with local transmission. Clinical presentation was variable. Half presented with symptoms not typical of a classical meningococcal disease, including two cases of cellulitis, which may have implications for clinicians, in terms of timely identification and treatment, and public health specialists, for offering timely antibiotic chemoprophylaxis to close contacts., (This article is copyright of The Authors, 2016.)

Purpose: Proposing an image reconstruction technique, algebraic reconstruction technique-refraction correction (ART-rc). The proposed method takes care of refractive index mismatches present in gel dosimeter scanner at the boundary, and also corrects for the interior ray refraction. Polymer gel dosimeters with high dose regions have higher refractive index and optical density compared to the background medium, these changes in refractive index at high dose results in interior ray bending., Methods: The inclusion of the effects of refraction is an important step in reconstruction of optical density in gel dosimeters. The proposed ray tracing algorithm models the interior multiple refraction at the inhomogeneities. Jacob's ray tracing algorithm has been modified to calculate the pathlengths of the ray that traverses through the higher dose regions. The algorithm computes the length of the ray in each pixel along its path and is used as the weight matrix. Algebraic reconstruction technique and pixel based reconstruction algorithms are used for solving the reconstruction problem. The proposed method is tested with numerical phantoms for various noise levels. The experimental dosimetric results are also presented., Results: The results show that the proposed scheme ART-rc is able to reconstruct optical density inside the dosimeter better than the results obtained using filtered backprojection and conventional algebraic reconstruction approaches. The quantitative improvement using ART-rc is evaluated using gamma-index. The refraction errors due to regions of different refractive indices are discussed. The effects of modeling of interior refraction in the dose region are presented., Conclusions: The errors propagated due to multiple refraction effects have been modeled and the improvements in reconstruction using proposed model is presented. The refractive index of the dosimeter has a mismatch with the surrounding medium (for dry air or water scanning). The algorithm reconstructs the dose profiles by estimating refractive indices of multiple inhomogeneities having different refractive indices and optical densities embedded in the dosimeter. This is achieved by tracking the path of the ray that traverses through the dosimeter. Extensive simulation studies have been carried out and results are found to be matching that of experimental results.

Background: Administration of convalescent plasma, serum, or hyperimmune immunoglobulin may be of clinical benefit for treatment of severe acute respiratory infections (SARIs) of viral etiology. We conducted a systematic review and exploratory meta-analysis to assess the overall evidence., Methods: Healthcare databases and sources of grey literature were searched in July 2013. All records were screened against the protocol eligibility criteria, using a 3-stage process. Data extraction and risk of bias assessments were undertaken., Results: We identified 32 studies of SARS coronavirus infection and severe influenza. Narrative analyses revealed consistent evidence for a reduction in mortality, especially when convalescent plasma is administered early after symptom onset. Exploratory post hoc meta-analysis showed a statistically significant reduction in the pooled odds of mortality following treatment, compared with placebo or no therapy (odds ratio, 0.25; 95% confidence interval, .14-.45; I(2) = 0%). Studies were commonly of low or very low quality, lacked control groups, and at moderate or high risk of bias. Sources of clinical and methodological heterogeneity were identified., Conclusions: Convalescent plasma may reduce mortality and appears safe. This therapy should be studied within the context of a well-designed clinical trial or other formal evaluation, including for treatment of Middle East respiratory syndrome coronavirus CoV infection., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

We audited adherence to national hepatitis B virus (HBV) immunisation policy for neonates and infants born to HBV positive mothers in two counties of England during 2007/08 to 2011/12 ( n =112 in County X, n =190 in County Y). Over the five year period, 29.9% of at risk neonates in County X and 23.5% in County Y required hepatitis B immunoglobulin (HBIG) at birth. The annual median age of HBIG administration was 0.0-0.5 days. The annual median coverage and timeliness of the first (coverage range 92.3-100.0%; age of administration range 0.0-0.0 days), second (83.8-100.0%; 32.0-42.0 days), third (81.1-100.0%; 62.0-81.0 days) and fourth dose HBV immunisations (44.4-91.9%; 378.0-443.0 days) and serological testing (8.6-81.0%; 450.0-707.0 days) were calculated. Statistically significant variation was found in the coverage of third and fourth dose immunisations in County Y, age of fourth dose immunisation in County X, and the coverage and timeliness of serological testing in both counties ( p < 0.05). HBIG and the first three HBV immunisations were commonly administered according to the national schedule. Fourth dose immunisations and serological tests showed poor adherence. We advocate public health interventions to improve immunisation programme outcomes and hepatitis B surface antigen testing., Competing Interests: Declaration of conflicting interests: The authors declare that there is no conflict of interest.

Concern is continuously raised about the safety of parabens which are present in most of the cosmetic preparations. In this investigation, methyl-, ethyl-, propyl- and butyl paraben (MP, EP, PP, BP), in a commercial cosmetic lotion, were deposited on human skin fragments, collected after surgical operations. Permeated parabens were determined after their passage through human epidermis-dermis layers, fixed on Franz diffusion cells. Bovine serum albumin (3%) was employed as receptor fluid. Then, parabens were assessed by liquid chromatography. The objective of this research was to determine the permeation of these molecules through human epidermis-dermis layers, and their possible passage to body tissues and/or accumulation in skin layers. Two groups of experiments were performed. In the first experimental group (G1), unique doses of the cosmetic were deposited on skin fragments fixed on Franz cells (n = 6), at time 0 h, followed with different withdrawn times of the receptor fluid at 12, 24 and 36 h. G1 results demonstrated that parabens penetration was influenced by their lipophilicity: more lipophilic the parabens were (BP > PP > EP > MP), less they crossed the skin layers (BP < PP < EP < MP). The second experimental group (G2) was constituted of three equal deposits on each Franz cell (n = 6) at different hour times 0, 12 and 24 h followed with three withdrawn times of the receptor fluid at 12, 24 and 36 h. The G2 results indicated that investigated parabens had significant increasing permeations in skin layers. This situation provokes the accumulation of these molecules which were considered by some authors as the cause of skin toxicities and carcinogenicity.

Ultraviolet irradiation causes adverse effects like sunburn, photosensitivity reactions or immunologic suppression. The aim of this study was to evaluate the photo-protective outcome of a sunscreen cream (SPF8) by the determination of erythema indexes and the assessment of ascorbic acid and its metabolites in human dermis. These substances were used as markers of oxidative effect. Eight healthy female subjects were enrolled in this study. Two abdominal areas were exposed to solar simulated irradiation with three minimal erythema dose, one with SPF8 application and the other site without SPF8 application. Two other areas were used as control, one without SPF8 application and the other site after SPF8 application. Ascorbic acid and its metabolites (dehydroascorbic acid, threonic acid, oxalic acid and xylose) were collected from human dermis by microdialysis and assessed by gas chromatography mass spectrometry. Irradiated site without sunscreen application had significantly demonstrated lower dermis ascorbic acid concentrations and a higher erythema index than the three other sites (P < 0.05). Threonic acid, oxalic acid and xylose dermis concentrations were significantly higher in site III than in the control site I (P < 0.05). The protected-irradiated site did not show erythema formation and there was stability of ascorbic acid dermis concentrations with non-variation in its metabolites. The assessment of ascorbic acid and its metabolites in human dermis could be an efficient tool to demonstrate the oxidative process and consequently to control the efficiency of sunscreen creams against undesirable UV effects.

Reactive oxygen species play an important role in inflammatory skin diseases such as psoriasis. Reactive oxygen species synthesis is catalysed by iron and some species are scavenged by ascorbic acid. The aim of this work was to assess iron and ascorbic acid in uninvolved and involved psoriatic dermis and to compare the corresponding concentrations in the dermis of healthy subjects. Microdialysis associated with atomic absorption spectrometry and gas chromatography-mass spectrometry was used to assess iron and ascorbic acid, respectively. Seven psoriatic patients and five healthy volunteers were studied. Iron concentrations in the involved (57.1 +/- 19.3 microg/l) and uninvolved (49.7 +/- 27.1 microgl/l) psoriatic dermis were higher than the corresponding value determined in the dermis of healthy subjects (21.8 +/- 2.4 microg/l) (p<0.05). Ascorbic acid in involved (47.3 +/- 8.2 microg/ml) and uninvolved (42.0 +/- 14.0 microg/ml) psoriatic dermis was statistically lower than that found in healthy dermis (176.8 +/- 29.0 microg/ml) (p<0.05). These results demonstrate that psoriatic patients exhibit high iron and low ascorbic acid concentrations in the dermis, but there were no significant differences between involved and uninvolved skin.

An outbreak of serogroup W-135 meningococcal disease occurred during the 2000 Hajj in Saudi Arabia. Disease was reported worldwide in Hajj pilgrims and their close contacts; however, most cases were identified in Saudi Arabia. Trends in Saudi meningococcal disease were evaluated and the epidemiology of Saudi cases from this outbreak described. Saudi national meningococcal disease incidence data for 1990 to 2000 were reviewed; cases from January 24 to June 5, 2000, were retrospectively reviewed. The 2000 Hajj outbreak consisted of distinct serogroup A and serogroup W-135 outbreaks. Of 253 identified cases in Saudi Arabia, 161 (64%) had serogroup identification; serogroups W-135 and A caused 93 (37%) and 60 (24%) cases with attack rates of 9 and 6 cases per 100,000 population, respectively. The 2000 Hajj outbreak was the first large serogroup W-135 meningococcal disease outbreak identified worldwide. Enhanced surveillance for serogroup W-135, especially in Africa, is essential to control this emerging epidemic disease.

Background: Reactive oxygen species (ROS) contribute to processes relating to cutaneous aging. Iron catalyses ROS formation whereas ascorbic acid (AA) plays a fundamental role in defending the organism against undesirable ROS action., Objective: The aim of this work was to determine the ex vivo iron and AA concentrations in human dermis from different age groups to better understand their role., Methods: Skin fragments were collected from 66 female patients during surgical operations and were grouped according to age: group I (<15 years, before puberty, n = 12), group II (15-50 years, adults, n = 42), and group III (>50 years, advanced age adults, n = 12). Two sites were investigated: the abdomen (unexposed areas) and face (exposed sites). Iron and AA were collected from human dermis by microdialysis and assessed by atomic absorption spectrometry and gas chromatography mass spectrometry, respectively., Results: Iron concentrations in the dermis were significantly higher in group III (27.4 +/- 20.9 microg/l) than in group I (13.8 +/- 3.3 microg/l; p< 0.05 ). An inverse correlation between AA dermis levels and increasing age was detected. For groups III and I, iron and AA concentrations were significantly different in dermis from the face compared to that of the abdomen (p < 0.05)., Conclusion: This study shows for the first time that there is a direct relationship between iron and AA concentrations in the dermis and aging. Moreover, iron and AA concentrations differed according to body site., (Copyright 2003 S. Karger AG, Basel)

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which reactive oxygen species (ROS) may be involved. Iron catalyses ROS formation and ascorbic acid (AA) scavenges these species., Objective: The aim of this work was to determine iron and AA levels in AD patients' dermis and to compare their concentrations with those of healthy volunteers' dermis., Methods: Five AD patients and 5 healthy subjects (controls) were enrolled in this study. Iron and AA were collected from human dermis by microdialysis and assessed by atomic absorption spectrometry and gas chromatography-mass spectrometry, respectively., Results: The AD dermis demonstrated higher iron concentrations (44.3 +/- 4.6 microg/l) compared to controls (21.8 +/- 1.2 microg/l) as well as a significantly lower concentration of AA (46.7 +/- 0.6 vs. 176.8 +/- 14.5 microg/ml, respectively)., Conclusion: These results suggest that iron and AA dermis levels could be indicators of inflammatory tissues and might be implicated in dermatological diseases such as AD., (Copyright 2003 S. Karger AG, Basel)

8-Methoxypsoralen (8-MOP) is currently used in PUVA therapy (psoralen+UVA) to treat dermatological diseases such as psoriasis, vitiligo and atopic dermatitis. The aim of this work was to validate a method for collecting 8-MOP from patient dermis by a non invasive technique, microdialysis, and then to assess this molecule by gas chromatography-mass spectrometry (GC-MS). 5-Methoxypsoralen (5-MOP) was used as an internal standard. The calibration curve demonstrated a linear relationship between the peak areas of 8-MOP and 5-MOP over a wide range of 8-MOP concentrations (0.9-100 ng/ml). Within- and between-run precisions were measured, using four different 8-MOP concentrations, which varied from 98.0 to 102.0% and from 98.5 to 101.8%, respectively. The limits of detection and quantification were 0.29 and 0.52 ng/ml, respectively. The method was validated and then applied to determine the pharmacokinetic of 8-MOP in ten psoriatic patient dermis, after oral intake of this drug. The results demonstrated that the association of microdialysis with the GC-MS method was an efficient procedure to collect and assess 8-MOP in human dermis, in vivo.

Until recently, the determination of metallic elements concentrations in normal skin, in vivo, was rare due to the lack of non-invasive techniques. Microdialysis has the advantage of being slightly invasive when applied to the collection in vivo of endogenous or exogenous substances from the skin. Iron is an active element in different cutaneous disorders. The aim of this work was to assess iron by atomic absorption spectrometry (AAS) after the collection of samples by microdialysis from human dermis. A first essential step, before determining the in vivo iron concentration in human dermis, was to establish an experimental protocol applicable to ex vivo as well as in vivo conditions. For this reason, this work deals only with the assessment of iron in ex vivo human dermis. A skin microdialysis technique and a calibration method, the No Net Flux, were used to quantify basal iron concentrations in human dermis and the same method was also used to determine in vitro and ex vivo iron recoveries. No differences were detected between in vitro and ex vivo recoveries. Ex vivo basal iron dermis concentrations ranged from 3.6 to 7.7 microg/l. This study shows that non-invasive microdialysis is an efficient method for sampling iron from human skin. A sensitive and accurate AAS technique was able to assess low iron concentrations in human dermis. The strategy adopted for this work was efficient and appropriate for the determination of iron in human skin and experiments will be carried out in vivo.

A simple and rapid high-performance thin-layer chromatographic (HPTLC) determination of 5-methoxypsoralen in serum is necessary for the therapeutic survey of patients treated with Puvatherapy (psoralen+UVA). The assay for this biological fluid involves an extraction with heptane-dichloromethane (4:1, v/v). The analytical method is linear from 50 to 250 ng/ml. This assay range is adequate for analysing human serum, as it corresponds to psoralen concentrations measured in serum from patients treated with psoralen and UVA against psoriasis and vitiligo. The limit of detection is 15 ng/ml. The coefficient of variation was less than 7%.

In medicine, psoriasis and vitiligo are most often treated with PUVA therapy (psoralen plus ultraviolet A). The determination of psoralen in patients' blood is necessary, as it is admitted that the therapeutic efficiency depends on drug concentration in patients' serum. The amount of UVA to administer is inversely proportional to serum peak concentration. High-performance liquid chromatography (HPLC) and gas chromatography are the most employed methods for determining psoralens in patients' serum. The 2 techniques are precise and very sensitive, but time consuming. The aim of this paper is to propose a suitable method which is rapid and simple. It is a spectrofluorimetric technique for 5-methoxypsoralen (5-MOP) determination in the serum of patients treated with PUVA therapy. 5-MOP extraction was carried out with an heptane/dichloromethane mixture (4/1; v/v), according to the Stolk method (1980). A calibration curve (CC) was plotted from 5-MOP concentrations (range 50, 100, 200, 300, 400, 500 ng/ml). The CC was linear with a good coefficient of correlation: r = 0.9971, and a suitable coefficient of variation (CV) of 7.0%. The recovery of the method ranged from 85.3 +/- 4.2 to 108 +/- 4.1%. The assay precision gave a CV ranging from 0.10 to 6.90%, with an error inferior to +/-10%. The method did not reveal any interference from serum components on the 5-MOP emission wavelength. The limit of detection of 5-MOP was 15 ng/ml. The proposed procedure was proved to be appropriate for a rapid determination of 5-MOP in patients' serum. This technique could also be employed for other psoralens used in PUVA therapy (e.g., 8-methoxypsoralen).

The aim of this study was to determine and to compare experimental and theoretical solubilities (S) as well as partition coefficients (PC) in an octanol/water system of psoralen (P), 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5',8-trimethylpsoralen (TMP). For each psoralen, experimental results were performed in triplicate with a spectrofluorimetric technique. The measurements were achieved 10 times for each solution. The obtained order of the solubilities in pure octanol was 5-MOP approximately TMP > P > 8-MOP, while in water-saturated octanol it was expressed as follows: TMP approximately 5-MOP > P > 8-MOP. However, the following order was found for hydrophobicity: TMP > 5-MOP > 8-MOP > P. The solubility ratios (SR) in pure octanol and water were assessed (mean +/- SD): 3.13 +/- 0.01 (P), 2.60 +/- 0.01 (8-MOP), 3.75 +/- 0.01 (5-MOP), and 5.11 +/- 0.01 (TMP). In saturated phases, they were 3.27 +/- 0.01, 2.63 +/- 0.01, 3.85 +/- 0.01, and 5.32 +/- 0.01, respectively. The PCs were determined with low concentrations according to the Dearden and Bresnen32 method and they were 1.67 +/- 0.01, 1.93 +/- 0.01, 2.00 +/- 0.01, and 3.14 +/- 0.01, respectively. Solubility parameters (delta), in Hildebrand unit (H) or in (cal/cm3)1/2, were evaluated. They confirmed the polarity of psoralens, previously expressed through the PC, although the positional isomers (5-MOP and 8-MOP) revealed no difference. Hildebrand's approach to the solubility of regular solutions and Yalkowsky's concept of the solubility of nonelectrolytes and weak electrolytes in an octanol/water system permitted a comparison of the theoretical and experimental results. The perspective of this work is to use the physicochemical properties of the psoralens in practice for insuring convenient experimental assays and the prediction, in vitro, of the percutaneous absorption of these compounds.

Since 1974, phototherapy with psoralen and ultraviolet A (UVA) has been used successfully for the treatment of psoriasis. However, undesirable side effects, including phototoxicity, nausea, stomach pain and headaches, have led investigators to develop new psoralen compounds. 5-Methoxypsoralen (5-MOP) has thus been introduced as an alternative to 8-MOP because of its less pronounced side effects. Since the absorption kinetics and bioactivity of 5-MOP are known to be variable, a new micronized tablet form (5-MOPm) has been developed. In an open randomized study, oral treatments with 5-MOP or 5-MOPm plus UVA radiation were compared in 22 psoriatic patients. Skin type and initial psoriasis area severity index did not differ significantly between treatment groups. Serum concentrations were significantly higher (320 vs 85.82 ng/ml) and occurred earlier (51.8 vs 229.09 min) with 5-MOPm. In addition, a reduction in PASI of more than 90% was achieved sooner (10.63 vs 17.27 treatments) and with a lower cumulative UVA dose (145.89 vs 232.11 J/cm2), in the group treated with 5-MOPm. No side effects were observed with 5-MOPm. Our data indicate that 5-MOPm has a higher bioavailability, clinical efficacy and tolerability than the commonly used 5-MOP.

The binding of 5-methoxypsoralen (5-MOP) to human serum and blood fractions was studied by equilibrium dialysis associated to high-performance liquid chromatography. 5-MOP serum binding was 95% and kept constant in the range of therapeutic concentrations. Albumin was the main binding protein with one class of binding sites (n = 2.05) and with a moderate affinity constant (Ka = 10,270 M-1). Free fatty acids (FFA) enhanced 5-MOP binding to albumin. Binding to other proteins, alpha 1-acid glycoprotein, gamma-globulins and lipoproteins (LDL, HDL, VLDL) also occurred, but was negligible. 5-MOP bound to red blood cells (RBCs) with a binding index (ratio of intra- to extra-globular 5-MOP concentrations) of 3.84 and 1.48 in buffer and plasma, respectively. 5-MOP distribution in blood was simulated. The free fraction of 5-MOP in blood could be increased in hypoalbuminemia, unchanged in acute inflammation, and decreased by FFA.

Human serum albumin is known to be the main carrier of 5-methoxypsoralen (5-MOP) in serum. As hypoalbuminaemia may occur in psoriasis with inflammatory syndrome, variability of the free 5-MOP fraction in serum can be expected. The free 5-MOP fraction was determined by equilibrium dialysis in serum samples obtained from 18 psoriatic patients and 18 control subjects. The median free 5-MOP fraction was not significantly different in the psoriatic group (fu = 4.75%) than in the control group (fu = 5%). However, there was a significantly larger variability of the free fraction in the psoriatic group (2.7 to 8.6%) than in the healthy group (3.2 to 6.8%) (p = 0.002). The binding index of 5-MOP (ratio of bound to free concentrations) was correlated with human serum albumin level (r = 0.784). This work confirms that the 5-MOP fraction in human serum is principally serum albumin dependent, as has been described with in vitro models. Free drug monitoring of 5-MOP is discussed.

A new tablet of micronized 5-methoxypsoralen (5-MOP) and a commonly used tablet in therapy (Psoraderm 5) were compared in 12 healthy subjects. Each subject ingested 1.2 mg/kg body weight of each formulation on different days. Bioavailability and phototoxicity of 5-MOP were compared. The results showed that serum and suction blister concentrations were significantly higher and occurred earlier after the oral intake of the micronized preparation. A series of graduated UVA doses were administered, one dose each time the concentration serum peaked, in order to determine the minimum phototoxic dose for each formulation. The micronized preparation induced greater photosensitivity than the unmicronized one. The micronized 5-MOP tablet may thus allow lower doses of UVA to achieve therapeutic results in photochemotherapy and a shortened waiting period following ingestion of drug.

Increasingly used in therapeutics, 5-methoxypsoralen (5-MOP), a linear furocoumarin, associated with UVA irradiation (PUVA), is now an established treatment for skin diseases such as vitiligo, mycosis funcoides and particularly psoriasis. Successful PUVA therapy depends on a sufficiently high peak 5-MOP plasma concentration coinciding with the UVA irradiation. However, as with most drugs, only the free plasma fraction is able to enter the target cells and has a pharmacological effect. In this work, the binding of 5-MOP to human albumin was studied in vitro, using a dialysis chamber. Bound and free 5-MOP fractions were quantified by a modification of Stolk's high-performance liquid chromatographic method. Dialysis was performed at 37 degrees C and pH 7.4 for 2 h, against a 4% albumin solution in phosphate buffer. The 5-MOP concentrations used were from 5 x 10(-5) to 5 x 10(-2) g/l in 1 x 10(-1) g/l steps. The 5-MOP bound strongly to human albumin in an unsaturable way. The mean 5-MOP binding to albumin was 95.3%. These results are in accordance with those published by Artuc et al. and not with those of Veronese et al., who found a lower saturable fixation (91%). These two research groups used tritiated 5-MOP. The technique used in this work is simple and inexpensive. It can be employed easily in vivo, e.g., for the assessment of 5-MOP free fractions in different therapeutic conditions.

The concentration of 5-methoxypsoralen (5-MOP) in suction blister fluid (SBF) after oral intake was determined in relation to the peak blistering point. Interstitial fluid was obtained from nine healthy male volunteers by applying mild suction (300-350 mmHg) to the skin of the volar aspect of the forearm. Blisters were raised at three different times: 18 h prior to drug administration (group I); 2 h prior to drug administration (group II); and during drug ingestion (group III). SBF levels of 5-MOP were determined in each group of blisters 2 h after oral administration of 1.2 mg/kg micronized 5-MOP. The results showed a statistically significant difference in the concentrations of 5-MOP between each group of blisters. The highest concentration of 5-MOP in the SBF was found in group III and the lowest in group II blisters. These findings suggest that the point of peak blistering in relation to drug administration needs to be known in each pharmacological study using suction blisters.

Diurnal variations in drug pharmacokinetics are a well known phenomenon. Chronopharmacology studies now appear to be attracting increasing interest with a view to establishing an optimum therapeutic prescription. In order to determine possible chronobiological variations of 5-methoxypsoralen (5-MOP) pharmacokinetic, 5-MOP blood concentrations were quantified in 8 healthy subjects after drug ingestion at different times during the day. Stolk's High Performance Liquid Chromatography technique was used to assess the 5-MOP serum concentrations. Each subject underwent three pharmacokinetic studies after oral ingestion of 5-MOP (1.2 mg/kg), in conjunction with a standardized low-lipid meal. The first pharmacokinetic study was started in the morning, the second in the afternoon and the third in the evening. Drug intake was at intervals of 2 days, to avoid drug accumulation. The results showed that the evening intake of the drug induced a higher 5-MOP maximum concentration and a higher 'area under curve' than morning or afternoon ingestion. This study suggests an optimized PUVA therapy, when performed in the evening.

The skin relief influences the exterior aspect of the skin which is very sensitive to aging. It could also be related to the mechanical properties and structure of both dermis and stratum corneum. Consequently, quantitative measurement of the skin surface roughness would seem most useful, as it would permit a quantification of skin aging, an in vivo analysis of mechanical forces acting on the skin structure, and the detection of abnormalities otherwise not visible. The method described comprises three steps: (1) making a silicone rubber negative replica, (2) making an Araldite positive cast, (3) roughness measurement of the cast with a device commonly used in engineering, which provides quantitative parameters: Ra, Rp, Rt, Rmax and others. The reliability of each of these steps was checked, and also the absolute need to locate precisely the site of sampling and to know the angle of the scanning direction with the main axis of the limb or the body. The method seems useful for studying aging, either normal or affected by UV rays and other physiopathological events influencing the skin surface.

Childhood (3 to 9 years) is a calm period of constant growth throughout which social contacts are discovered and intelligence and discretion take place. Consequently, most diseases are infectious. Microrelief was found twice shallower and skin (epidermis + dermis) twice thinner than in adults. Intervals between furrows were reduced parallel to total body surface, thus ruling out the possible existence of special shelters favouring bacterial growth. Sweating is lower, as are skin surface lipid levels, in contrast to the post-natal period, inducing dryness of skin. Although total skin stiffness in vivo was found to be identical to young adult skin, skin chapping is much more frequent. Since detergents as well as extended hot baths may reduce the stratum corneum water binding capacity, they should be used with discretion. Hence, skin care in this period of age should be based upon different criteria than in adults.