RESUMEN
There is a very vital antioxidant extracted from microgreen alga. Chlorella vulgaris has major advantages and requires high yield worldwide. Some microalgae require vitamins for their growth promotion. This study was held to determine the impact of different vitamins including Thiamine (B1), Riboflavin (B2), Pyridoxine (B6), and Ascorbic acid (c) at concentrations of 0.02, 0.04, 0.06, and 0.08 mg/L of each. Each vitamin was added to the BG11 growth medium to determine the effect on growth, total carbohydrate, total protein, pigments content, antioxidant activities of Chlorella vulgaris. Moreover, antitumor effects of methanol extract of C. vulgaris without and with the supplement of thiamine against Human prostate cancer (PC-3), Hepatocellular carcinoma (HEPG-2), Colorectal carcinoma (HCT-116) and Epitheliod Carcinoma (Hela) was estimated in vitro. C. vulgaris supplemented with various vitamins showed a significant increase in biomass, pigment content, total protein, and total carbohydrates in comparison to the control. Thiamine was the best vitamin influencing as an antioxidant. C. vulgaris supplemented with thiamine had high antitumor effects in vitro. So, it's necessary to add vitamins to BG11 media for enhancement of the growth and metabolites.
Asunto(s)
Chlorella vulgaris , Microalgas , Antioxidantes/metabolismo , Antioxidantes/farmacología , Biomasa , Chlorella vulgaris/metabolismo , Humanos , Masculino , Tiamina , Vitaminas/metabolismo , Vitaminas/farmacologíaRESUMEN
BACKGROUND/OBJECTIVES: Despite the apparent efficacy and favorable toxicity profile of TKIs, allogeneic SCT remains the only curative treatment for CML especially in younger patients, but TRM should be considered. We evaluated the clinical outcomes of pediatric CML patients who had SCT in our center. METHODS: This retrospective study included children with CML, who received an allogeneic SCT at Children Cancer Hospital Egypt, 57357, from 2007 to 2017. All patients received myeloablative conditioning chemotherapy containing busulfan/cyclophosphamide followed by stem cell infusion from MRD. RESULTS: From 121 patients diagnosed with CML, 43 had available MRD and subjected to HSCT while 78 patients continued TKI therapy. The median time to transplant from diagnosis was 13 months. At initial diagnosis, there were 39 patients in CP and 4 had blastic crises. Bone marrow harvest was the stem cell source in 32 patients, while 11 cases received mobilized peripheral blood stem cells with average stem cell dose of 4.45 × 106 /kg. The probabilities of overall survival and event-free survival at 5 years were 97.4% and 79.8%, respectively. TRM at 100 days and TRM at 1-year post-transplant were 0%. The incidence of chronic GVHD was significantly higher in peripheral blood than bone marrow stem cell source (P = .004). CONCLUSION: Considering the excellent survival rates and very low TRM, HSCT is still a valid option for pediatric patients with newly diagnosed CML with best using marrow stem cell source to avoid a significant risk of cGVHD and its related complications.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios Retrospectivos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Children with acute leukemia may experience high treatment-related mortality, which often occurs early in the induction phase. The aim of the study was to assess the incidence and risk factors related to increased mortality during induction therapy of pediatric patients with acute leukemia. This is a retrospective study that included pediatric acute leukemia patients who presented to the National Cancer Institute, Cairo University, between January 2011 and December 2013. The study included 370 patients, 253 with acute lymphoblastic leukemia, 100 with acute myeloid leukemia, and 17 with mixed phenotype acute leukemia. The total and induction death rates were 40.5% and 19.2%, respectively. Most of the early deaths were attributed to infections (64.7%) and cerebrovascular accidents (18.3%). Using enhanced supportive care measures during 2013 had significantly reduced the overall and induction mortality rates (29% and 13.6%, respectively, in 2013 vs. 46% and 20.3% in 2011). Induction deaths in pediatric acute leukemia remain a major challenge in developing countries, and using enhanced supportive care measures is effective to improve the survival outcome in this group of patients.
Asunto(s)
Leucemia/mortalidad , Enfermedad Aguda , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Estudios de Cohortes , Países en Desarrollo , Egipto/epidemiología , Femenino , Humanos , Incidencia , Lactante , Leucemia/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
The lumbar artery perforator (LAP) flap is a relatively new procedure that can be utilized to manage lumbosacral defects in addition to reconstructing distal body parts as well, such as breast reconstruction. This fasciocutaneous flap is designed based on the LAPs small arteries that emerge from the lumbar arteries then move superficially piercing overlying tissues to perforate the lumbar fascia and supply the skin and subcutaneous tissue; However, anatomical and clinical studies regarding the LAP flap and its perforators are sparse in the literature, and the results are even contradicting. This article will discuss the LAP flap, the anatomy of its perforators, and the clinical aspects about its usage. In addition, we explore its preoperative imaging evaluation, and deliver a guide on image reporting and radiological data that will benefit the surgeon most during the procedure.
Asunto(s)
Región Lumbosacra/irrigación sanguínea , Colgajo Perforante/irrigación sanguínea , Arterias/anatomía & histología , Arterias/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Humanos , Imagenología Tridimensional , Región Lumbosacra/diagnóstico por imagen , Cuidados PreoperatoriosRESUMEN
The possibility of delaying treatment of HCV due to severe thrombocytopenia is challenging. This study aimed to detect the prevalence of active helicobacter infection as a claimed cause of thrombocytopenia in a cohort of Egyptian patients with chronic active HCV awaiting combined anti-viral therapy. The study included 400 chronic HCV patients with thrombocytopenia. Laboratory investigations included liver function tests, real time quantitative PCR, reticulocytic count, ESR, ANA, bone marrow aspiration, measurement of anti-helicobacter antibodies, and helicobacter stool antigen. Positive cases for active H. pylori were given the standard triple therapy for 2 weeks. Helicobacter stool antigen was detected 4 weeks after termination of therapy and the change in platelet count was detected 1 month after eradication. A total of 248 out of 281 seropositive patients for H. pylori (88.3 %) showed positive stool antigen (p = 0.01). Eradication was achieved in 169 (68.1 %) patients with platelet mean count 114.9 ± 18.8 × 10(3)/µl with highly significant statistical difference from pretreatment value (49.7 ± 9.2 × 10(3)/µl, p = 0.000). Seventy-nine patients were resistant to conventional triple therapy and given a 7-day course of moxifloxacin-based therapy; 61 patients responded (77.1 %) with mean platelet improvement from 76.4 ± 17.4 × 10(3)/µl to 104.2 ± 15.2 × 10(3)/µl (p = 0.000). The non-responders showed no improvement in their platelet count (74.6 ± 20.5 vs. 73.6 ± 15.3 × 10(3)/ul, P = 0.5). Eradication of active H. pylori in HCV augments platelet count and enhances the early start of antiviral therapy.
Asunto(s)
Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Helicobacter pylori , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Trombocitopenia/complicaciones , Adulto , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Estudios de Casos y Controles , Quimioterapia Combinada , Egipto , Femenino , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Prevalencia , Trombocitopenia/sangre , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiología , Resultado del TratamientoRESUMEN
STUDY QUESTION: Is it possible to perform allogeneic uterus transplantation (UTx) with a donation from a live donor in a non-human primate species and what immunosuppression is needed to prevent rejection? SUMMARY ANSWER: Allogeneic UTx in the baboon is a donor- and recipient-safe surgical procedure; immunosuppression with induction therapy and a triple protocol should be used. WHAT IS KNOWN ALREADY: UTx may become a treatment for absolute uterine factor infertility. Autologous UTx models have been developed in non-human primates with reports on long-term survival of the uterine grafts. STUDY DESIGN, SIZEAND DURATION: This experimental study included 18 female baboons as uterus donors and 18 female baboons as uterus recipients. The follow-up time was 5-8 weeks. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Uterus retrieval was performed with extended hysterectomy including bilateral uterine and internal iliac arteries and ovarian veins. After UTx, with vascular anastomoses unilateral to the internal iliac artery and the external iliac vein, the uterus recipients received one of the following: no immunosuppression (n = 4); monotherapy (oral slow release tacrolimus) (n = 4) or induction therapy (antithymocyte globulin) followed by triple therapy (tacrolimus, mycophenolate, corticosteroids; n = 10). Surgical parameters, survival, immunosuppression and rejection patterns were evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: The durations of uterus retrieval and recipient surgery were around 3 and 3.5 h, respectively. The total ischemic time was around 3 h. All the recipients and the donors survived the surgery. All the recipients presented rejection to some extent within the first weeks following UTx. In one recipient, the uterus was of normal appearance at the end of the study period. In spite of occasional high (>60 ng/ml) blood levels of tacrolimus, there was no evidence of nephrotoxicity. LIMITATIONS AND REASONS FOR CAUTION: This initial non-human primate allogeneic UTx study indicates that further research is needed to optimize immunosuppression protocols in order to avoid uterine rejection. WIDER IMPLICATIONS OF THE FINDINGS: The findings suggest that allogeneic UTx in primate species is feasible but continued work on this issue is needed. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Swedish Research Council, ALF University of Gothenburg, Hjalmar Svensson Foundation and by Jane and Dan Olsson Research Foundation. The authors do not have any competing interest.
Asunto(s)
Modelos Animales de Enfermedad , Terapia de Inmunosupresión/métodos , Quimioterapia de Inducción , Infertilidad Femenina/cirugía , Enfermedades Uterinas/fisiopatología , Útero/trasplante , Corticoesteroides/uso terapéutico , Animales , Suero Antilinfocítico/uso terapéutico , Quimioterapia Combinada , Estudios de Factibilidad , Femenino , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Infertilidad Femenina/etiología , Donadores Vivos , Quimioterapia de Mantención , Ácido Micofenólico/uso terapéutico , Papio , Tacrolimus/uso terapéutico , Trasplante Homólogo , Útero/inmunologíaRESUMEN
BACKGROUND: Uterus transplantation (UTx) may provide the first available treatment for women affected by uterine infertility. The present study aimed to further develop a surgical technique for autologous UTx in a non-human primate species and to assess long-term function. METHODS: Female baboons (n= 16) underwent autologous transplantation of the uterus with the Fallopian tubes and ovaries, performed with a previously published surgical technique (n= 6, Group 1) or using a modified technique (n= 10; Group 2). The uterine arteries were dissected to the proximal end of the anterior branch (Group 1) or the entire (Group 2) internal iliac artery, and the ovarian veins were dissected to the crossing over the ureter (Group 1) or further cranially to include greater lengths and patches of the cava/renal vein (Group 2). Back-table preparation created common venous and arterial ends with arterial anastomosis either end-to-side to the left external iliac artery (Group 1) or end-to-end to the left internal iliac artery (Group 2). RESULTS: Overall short-time survival of the animals was 88% (66% in Group 1 and 100% in Group 2). Of all the operated animals, 75% (66% in Group 1 and 80% in Group 2) resumed ovarian cyclicity. Regular menstruation after UTx was demonstrated only in Group 2 (60%). Menstruating animals (n= 6) were each exposed to timed mating for ≥5 menstrual cycles, but pregnancy did not occur. Adhesions and tubal blockage were seen in post-mortem analysis. CONCLUSIONS: The modified UTx model of Group 2 is a safe procedure and shows resumed long-term uterine function in a majority of the animals, although pregnancy could not be demonstrated.
Asunto(s)
Papio , Útero/trasplante , Animales , Arterias/cirugía , Cruzamiento , Trompas Uterinas/trasplante , Femenino , Estudios de Seguimiento , Arteria Ilíaca/cirugía , Menstruación , Ovario/irrigación sanguínea , Ovario/trasplante , Embarazo , Trasplante Autólogo/métodos , Trasplante Autólogo/veterinaria , Resultado del Tratamiento , Útero/irrigación sanguínea , Venas/cirugíaRESUMEN
The purpose of this study was to assess the clinical and radiological patterns and outcome predictors of posterior reversible encephalopathy syndrome (PRES) in pediatric cancer patients. A retrospective study included patients who developed PRES during their treatment at the Children's Cancer Hospital Egypt. A total of 50 patients developed PRES. Leukemia and lymphoma were the commonest diagnoses (64%). Regarding the MRI findings, occipital affection was the most common (92%), followed by frontal and temporal lobes involvement in 32% and 22% respectively and advanced PRES was described in 8 patients. Of the whole patients, 80% had complete clinical resolution and 60% showed complete radiological resolution at 2 weeks' evaluation and 2 patients died out of PRES. Unfavorable outcome was associated with those who had motor dysfunction, status epilepticus at presentation, frontal lobe and thalamic affection and atypical PRES. PRES might present in atypical sites with poor outcome including death.
Asunto(s)
Neoplasias , Síndrome de Leucoencefalopatía Posterior , Niño , Egipto , Humanos , Imagen por Resonancia Magnética , Neoplasias/complicaciones , Neoplasias/diagnóstico , Síndrome de Leucoencefalopatía Posterior/diagnóstico por imagen , Síndrome de Leucoencefalopatía Posterior/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Paracetamol is extensively consumed as an analgesic and antipyretic drug, but at a high dose level, it leads to deleterious side effects, such as hepatic and nephrotoxicity. This research aimed to estimate the prophylactic efficacy of Chlorella vulgaris and/or thiamine against paracetamol (P) induced hepatorenal and cardiac toxicity. Forty-eight female Wistar rats were randomly divided into eight equal groups (n = 6 rats). Group 1, normal control group. Group 2, Paracetamol group. Groups 3, 4 and 5 were treated with Silymarin drug, Chlorella vulgaris alga, Chlorella vulgaris alga supplemented with thiamine, respectively daily for 7 successive days, then all were administered Paracetamol (2gm/kg. bwt.). While, Groups 6, 7 and 8 were treated by Silymarin, Chlorella vulgaris alga, Chlorella vulgaris supplemented with thiamine, respectively daily for 7 successive days without paracetamol administration. Our results clarified that Paracetamol toxicity caused significant adverse effects on hematological, serum biochemical parameters, and oxidant -antioxidant status as well as histopathological picture of heart, liver, and kidney. However, in the Paracetamol intoxicated groups pretreatment either with Chlorella vulgaris alone or plus thiamine successfully improved the undesirable deleterious effects of paracetamol, and restored almost all variables to near their control levels. This study has finished to that oxidative stress participates in the pathogenesis of paracetamol-induced toxicity in rats and using Chlorella vulgaris alga either alone or plus thiamine alongside their health benefits can protect against oxidative harmful effects induced by paracetamol through their free radical scavenging and powerful antioxidant effects, and they can be used as propylactic agents against paracetamol-induced toxicity.
Asunto(s)
Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Chlorella vulgaris , Enfermedades Renales/prevención & control , Animales , Cardiotoxicidad/prevención & control , Suplementos Dietéticos , Femenino , Enfermedades Renales/inducido químicamente , Peroxidación de Lípido , Ratas WistarRESUMEN
BACKGROUND: Transplantation of the uterus has been suggested as a treatment of uterine factor infertility. This study investigates whether the sheep uterus can resume its capacity to harbour normal pregnancies after autotransplantation by vascular anastomosis. METHODS: From 14 ewes, the uterus, excluding one uterine horn, was isolated along with its oviduct and ovary and preserved ex vivo and then transplanted back with end-to-side anastomosis of the vessels of the graft to the external iliac vessels. After recovery, the ewes underwent surgical examination and serum progesterone measurements to ascertain healing and ovarian activity. Afterwards, five autotransplanted and five control ewes were placed with a ram for mating. Caesarean sections were performed before the estimated term of pregnancy and data on fetal measures were compared. RESULTS: Of the 14 ewes, seven survived surgery with ovarian activity intact and grafts showing normal appearance. Mating occurred in four of five transplanted ewes and in five out of five controls, and three transplanted animals and five control animals conceived. In one transplanted ewe, torsion of the uterus was observed after spontaneous initiation of labour. Foeti from transplanted mothers were comparable in size to those of controls. CONCLUSIONS: Despite the encountered complications, this is the first report to demonstrate fertility and pregnancies going to term after autotransplantation of the uterus in an animal of a comparable size to the human.
Asunto(s)
Trompas Uterinas/trasplante , Fertilidad , Ovario/trasplante , Útero/trasplante , Anastomosis Quirúrgica , Animales , Trompas Uterinas/irrigación sanguínea , Trompas Uterinas/fisiología , Trompas Uterinas/cirugía , Femenino , Vena Ilíaca/cirugía , Ovario/irrigación sanguínea , Ovario/fisiología , Ovario/cirugía , Embarazo , Ovinos , Trasplante Autólogo , Útero/irrigación sanguínea , Útero/fisiología , Útero/cirugíaRESUMEN
The synthesis of 2,2'-dihydroxy-3,3'-di(carboxymethyl)-1,1'-binaphthyl (H2L) and its novel metal complexes with Co(II), Ni(II), Fe(III) and Th(IV) salts are reported. The ligand and its metal complexes have been characterized on the basis of analytical, conductance, spectral (IR, UV-vis, 1H NMR, mass) and magnetic susceptibility measurements. The Mössbauer spectrum of the Fe(III) complex indicates a low-spin octahedral geometry around the Fe(III) ion. The IR and 1H NMR spectral data show that the ligand behaves in a dibasic bidentate fashion coordinating to two metal atoms through the two deprotonated naphthyl OH groups and acts in a dibasic tetradentate manner using both carbonyl oxygen's and the deprotonated naphthyl OH groups coordinating to two metal ions. Thermal studies (TGA, DTA) confirm the presence of solvents either inside or outside the coordination sphere and support the mechanism of the decomposition process. The value of [alpha]D20 for the ligand has been determined in DMSO.
Asunto(s)
Cobalto/química , Hierro/química , Naftalenos/química , Níquel/química , Espectrofotometría/métodos , Torio/química , Enlace de Hidrógeno , Hidróxidos/química , Ligandos , Espectroscopía de Resonancia Magnética/métodos , Espectrometría de Masas/métodos , Metales , Modelos Químicos , Espectrofotometría Infrarroja/métodos , Espectrofotometría Ultravioleta/métodos , Espectroscopía de Mossbauer/métodosRESUMEN
An increasing number of newly developed drugs show bioavailability problems due to poor water solubility. Formulating the drugs as nanosuspensions may help to overcome these problems by increasing saturation solubility and dissolution velocity. In the present study the bioavailability of the poorly soluble fenofibrate following oral administration was investigated in rats. Four formulations were tested: a nanosuspension type DissoCube(R), one solid lipid nanoparticle (SLN) preparation and two suspensions of micronized fenofibrate as reference formulations, one suspension in sirupus simplex and a second in a solution of hydroxyethy-cellulose in physiological saline. Both colloidal drug delivery systems showed approximately two-fold bioavailability enhancements in terms of rate and extent compared to the reference formulations. No significant differences were found in AUC(0-22 h) as well as in C(max) and t(max) between the two colloidal delivery systems. In conclusion, nanosuspensions may be a suitable delivery system to improve the bioavailability of drugs with low water solubility.
Asunto(s)
Fenofibrato/farmacocinética , Hipolipemiantes/farmacocinética , Nanopartículas/administración & dosificación , Administración Oral , Animales , Disponibilidad Biológica , Simulación por Computador , Fenofibrato/administración & dosificación , Fenofibrato/sangre , Hipolipemiantes/administración & dosificación , Hipolipemiantes/sangre , Lípidos/administración & dosificación , Masculino , Modelos Biológicos , Ratas , Ratas Wistar , Solubilidad , Suspensiones , Distribución TisularRESUMEN
At Kafr El-Sheikh province, Egypt, out of 117 examined drafting horses, mites were detected in 20 (17.09%) horses. The recovered mites were 14 Chorioptes, four Psoroptes and two Sarcoptes whereas mites were not detected in four cases clinically showed typical mange lesions. Interestingly, neither the age nor the sex of the examined horses had a clear influence on the prevalence of the infection. Clinical signs observed in mange infested horses were in the form of irregular skin lesions, severe itching and sometimes biting of affected skin areas and decrease feed consumption. The skin lesions mainly start as erythematous area followed by developing of papules and crust formation. Skin scratches as a result of traumatized lesions usually occurred. Hair was lost on the affected parts developing irregular alopecic areas. Distribution of the lesions was varied according to the type of mite. Chorioptic mite was detected in para-anal fold, distal portion of legs and tail lesions, Psoroptic mite was detected in withers, mane, shoulder and flank lesions whereas Sarcoptic mite was isolated mainly from lesions on the head and neck. Complete clinical and parasitological cure for mite infestation were obtained within 2 weeks in both moxidectin and ivermectin treated groups with 100% recovery rate. Our results indicated that moxidectin oral gel is effective and good alternative for the treatment of chorioptic mange in horse to avoid drug resistance that may develop as a result of the intensive use of ivermectin alone for long periods.
Asunto(s)
Enfermedades de los Caballos/tratamiento farmacológico , Enfermedades de los Caballos/patología , Insecticidas/uso terapéutico , Infestaciones por Ácaros/veterinaria , Administración Oral , Factores de Edad , Animales , Egipto , Femenino , Caballos , Resistencia a los Insecticidas , Ivermectina/uso terapéutico , Macrólidos/uso terapéutico , Masculino , Infestaciones por Ácaros/tratamiento farmacológico , Infestaciones por Ácaros/patología , Ácaros , Factores Sexuales , Resultado del TratamientoRESUMEN
The aim of the present study was to design and evaluate a chronomodulated time-clock pulsatile tablets of valsartan to release it after a certain lag time, independent of the gastrointestinal pH, in its absorption window to cope with the circadian rhythm of human body for blood pressure elevation. Core tablets were prepared by direct compression of a homogenous mixture of valsartan, Avicel PH101, croscarmellose sodium, magnesium stearate and Aerosil. The core tablets were then sprayed coated with a sealing layer formed of ethyl cellulose that was subsequently coated with a release-controlling layer. Three different aqueous dispersions namely; carnauba wax or beeswax or a mixture in a ratio of 2.5:1, respectively, were used to form five time-clock tablet formulations having the release controlling layer with different thickness {B5, B10, B20, BW5 and CW5}. Quality control testing were carried out to the core tablets. Differential scanning calorimetry was also performed to detect the possible drug excipient interaction in the core tablet formulation. The release was carried out, for the prepared time-clock tablet formulations, in 0.1 N hydrochloric acid for the first 2 h, followed by phosphate buffer (pH 6.8) for 4.5 h. The effect of pH on valsartan release was studied through a release study in 0.1 N hydrochloric acid for 6.5 h. Two phase dissolution study was performed to the selected time-clock tablet formulation to predict the drug permeation through the gastrointestinal tract. Stability study of the selected formula was performed at 25°/60% RH and at 40°/75% RH for 3 months. Results showed that a release-controlling layer composed of a mixture of carnauba wax and beeswax in a ratio of 2.5:1 showed a reasonable release lag time. The release lag time of the tablets increased with the increase of the coat thickness, thus B20>B10>B5 with corresponding lag time values of 4.5, 3 and 2.5 h, respectively. Selected B5 tablet formula exhibited a reasonable lag time after which the highest, complete % drug release at pH 6.8 was obtained. In addition, a good partitioning of valsartan, between the aqueous and organic phases in a ratio of 1:7, was observed. The selected formula was stable for at least 3 months under standard long-term and accelerated storage conditions. In conclusion, in vitro studies revealed that the novel time-clock system could be used successfully to deliver valsartan in a pulsatile pH-independent manner. It provided a desirable lag time followed by a rapid and complete drug release accompanied by an expected effective permeation through the biological membranes upon release in the duodenum; the window of absorption, as indicated by the two phase release study.
RESUMEN
The intestine, primarily regarded as an absorptive organ, is also prepared for the elimination of certain organic acids, bases and neutral compounds depending on their affinity to intestinal carrier systems. Several of the transport systems known to mediate efflux in the major clearing organs--liver and kidney--are also expressed in the intestine. Examples of secretory transporters in the intestine are P-glycoprotein, members of the multidrug resistance associated protein family, breast cancer resistance protein, organic cation transporters and members of the organic anion polypeptide family. In this communication, the P-glycoprotein mediated intestinal secretion of talinolol, a model compound showing metabolic stability, has been investigated in the jejunum, ileum and colon of rat intestine by single-pass perfusion. A model has been developed which demonstrates an increase in carrier-mediated secretion in the order jejunumAsunto(s)
Interacciones Alimento-Droga
, Absorción Intestinal/fisiología
, Mucosa Intestinal/metabolismo
, Preparaciones Farmacéuticas/metabolismo
, Animales
, Portadores de Fármacos
, Humanos
, Ratas
RESUMEN
To identify hospital occupational categories at potential risk of hepatitis B virus infection, a serologic survey was conducted for hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) by enzyme-linked immunosorbent assay in 765 employees at 4 hospitals in Cairo, Egypt. Overall, 3% HBsAg and 28% anti-HBs seromarkers. Combined HBsAg and anti-HBs frequencies by occupational group were: nonprofessional staff (60%), dentists (32%), graduate nurses (33%), physicians (29%), and student nurses (26%). The main risk factors for hepatitis B infection were frequency of exposure to patients' blood (for physicians, p less than 0.001) and to patients with jaundice (for dentists, p less than 0.01), and years of exposure to patients, as reflected by duration of occupation (for physicians, p less than 0.001) and by age of health care worker. Seropositivity by sex was greater for males (p less than 0.01). Physician specialties with highest risk of infection (29 to 53%) were surgery, infectious diseases, obstetrics-gynecology, and emergency medicine.
Asunto(s)
Hepatitis B/epidemiología , Enfermedades Profesionales/epidemiología , Personal de Hospital , Adolescente , Adulto , Factores de Edad , Egipto/epidemiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Anticuerpos contra la Hepatitis B/análisis , Antígenos de Superficie de la Hepatitis B/análisis , Humanos , Masculino , Factores de Riesgo , Factores SexualesRESUMEN
While premature death in schizophrenia is well recognised, mortality risk has received little longitudinal study in relation to population representativeness and patient engagement with health services. Within a rural Irish catchment area of socioeconomic, ethnic and geographical homogeneity and low residential mobility, an epidemiologically complete population of 72 patients with schizophrenia was followed up over 7.5 years in order to quantify mortality prospectively. Information was obtained in relation to 99% of the cohort, with 94% of those surviving retained in engagement with psychiatric care. There were 25 deaths (35% of cohort). A relative risk of 2.06 (95% CI, 1.40-2.80; P < 0.001) among this epidemiologically complete population may constitute an estimate of risk for mortality inherent to schizophrenia when disengagement from health services, residential mobility and socioeconomic, ethnic and geographical diversity are minimised. On long-term prospective evaluation, risk for death in schizophrenia was doubled on a background of enduring engagement in psychiatric care with increasing provision of community-based services and introduction of second-generation antipsychotics.
Asunto(s)
Servicios Comunitarios de Salud Mental/estadística & datos numéricos , Psicotrópicos/uso terapéutico , Salud Rural/estadística & datos numéricos , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/mortalidad , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Áreas de Influencia de Salud , Femenino , Estudios de Seguimiento , Humanos , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Medición de RiesgoRESUMEN
The expression of P-glycoprotein is induced in cell cultures upon exposure to various inducers. Therefore, the aim of the present study was to evaluate the in-vivo relevance of this observation, i.e. the influence of chronic pretreatments with selected drugs -- all of which are ligands to P-glycoprotein (P-gp) as demonstrated in radioligand binding studies and all of which have some or a considerable effect on P-gp expression in Caco-2 cells -- on the effective intestinal permeabilities of the model compound talinolol in rats employing in-situ single-pass intestinal perfusion of three different gut segments. Talinolol was selected, because it shows high selectivity for one of the exsorptive transporters (P-gp) and its intestinal permeability is very sensitive to changes in exsorption when the perfusate concentration is low. Prior to the induction study the perfusion model was optimized regarding the type and concentration of a competitive inhibitor which may be used to block the exsorption-related permeability reduction (through intestinal exsorption) during an ongoing perfusion and would permit an intra-individual comparison of the effective permeability without and with blockade of exsorption. While repetitive verapamil and talinolol dosing had no statistically significant exsorption-inducing effect, vinblastine and rifampicin pretreatments resulted in decreased intestinal talinolol permeabilities in the three tested gut segments, duodenum, jejunum, and colon [e.g., S-talinolol in jejunum: control, 2.50 x 10(-4) cm/s; vinblastine induction, 1.48 x 10(-4) cm/s (P<0.05); rifampicin induction, 1.51 x 10(-4) cm/s (P<0.05)]. Addition of an efficient secretion inhibitor (vinblastine) to the perfusate permitted the determination of the impact of inhibitable secretory processes on the total effective permeabilities and an estimation of passive permeability in the respective individual. The inhibitable permeability fractions were higher for vinblastine than for any other pretreatment and the difference from control pretreatment was statistically significant for all intestinal segments (duodenum, 61.8%; jejunum, 63.1%; colon, 43,7%; S-talinolol). Statistically significant differences were also detected for rifampicin in the perfused duodenum and jejunum (33.1 and 27.5% increase in inhibitable fraction, respectively, for S-talinolol). These differences are explained by a significant induction of outside-directed transport in the intestinal enterocytes by vinblastine and rifampicin.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacocinética , Colon/efectos de los fármacos , Duodeno/efectos de los fármacos , Yeyuno/efectos de los fármacos , Propanolaminas/farmacocinética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Animales , Antineoplásicos Fitogénicos/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Colon/metabolismo , Duodeno/metabolismo , Yeyuno/metabolismo , Ligandos , Masculino , Ratas , Ratas Wistar , Estereoisomerismo , Verapamilo/farmacología , Vinblastina/farmacologíaRESUMEN
Among the different application routes peroral administration remains the one most widely used. Hence, mechanisms affecting p.o. bioavailability are of particular interest, also in drug development. In recent years, intestinal drug secretion mediated by the multi-drug resistance gene product P-glycoprotein (Pgp) has been discovered as a possible mechanism of low and erratic bioavailability. Due to the saturability of this process, a dose-dependent apparent oral clearance may be observed which decreases upon increasing dose. However, in vivo intestinal secretion might be revealed only in the lower or subtherapeutic dose range. In permeability studies with Caco-2 cell monolayers, the MDR-reversing agent verapamil inhibits secretion of P-glycoprotein substrates and, hence, increases apical-to-basolateral permeability. The aim of the rat studies with talinolol presented here was to test the relevance of the intestinal secretion process as well as the extent of inhibition by verapamil in ex vivo, in situ, and in vivo talinolol/verapamil drug-drug interaction studies. Intestinal secretion of talinolol was detected indirectly in ex vivo studies via transport inhibition with verapamil and directly in in situ intestinal perfusions in rats following a talinolol i.v. bolus. Both i.v. and p.o. verapamil appear to affect the concentration-time profiles of talinolol. Relevant observations with respect to drug absorption are the decreased apparent oral clearance upon verapamil coadministration as well as the decreased tmax and mean absorption times at high verapamil doses. Talinolol may be regarded as a potential model compound for mechanistic studies on Pgp interactions, including permeability as well as binding studies and the involvement of transporters other than Pgp.