Pentoxifylline as Add-On Treatment to Donepezil in Copper Sulphate-Induced Alzheimer's Disease-Like Neurodegeneration in Rats.

Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by behavioral, cognitive, and progressive memory impairments. Extensive neuronal loss, extracellular accumulation of insoluble senile amyloid-ß (Aß) plaques, and intracellular neurofibrillary tangles (NFTs) are the major pathological features. The present study aimed to investigate the therapeutic effect of donepezil (DON) and pentoxifylline (PTX) in combination to combat the neurodegenerative disorders (experimental AD) induced by CuSO4 intake in experimental rats. Thirty adult male Wistar rats (140-160 g) were used in this study. AD was first induced in rats by CuSO4 supplement to drinking water (10 mg/L) for 14 weeks. The AD group received no further treatment. Oral treatment with DON (10 mg/kg/day), PTX (100 mg/kg/day), or DON + PTX for the other three groups was started from the 10th week of CuSO4 intake for 4 weeks. Cortex markers like acetylcholine (ACh), acetylcholinesterase (AChE), total antioxidant capacity (TAC), and malondialdehyde (MDA) and hippocampus markers like ß-amyloid precursor protein cleaving enzyme 1 (BACE1), phosphorylated Tau (p-tau), Clusterin (CLU), tumor necrosis factor-α (TNF-α), caspase-9 (CAS-9), Bax, and Bcl-2 were measured. The histopathology studies were done by using hematoxylin and eosin and Congo red stains as well as immunohistochemistry for neurofilament. CuSO4 induced adverse histological and biochemical changes. The histological injury in the hippocampus was inhibited following the administration of the DON and PTX. The brain tissue levels of AChE, MDA, BACE1, p-tau, CLU, CAS-9, Bax, and TNF-α were significantly increased, while brain tissue levels of ACh, TAC, and Bcl-2 were significantly decreased in CuSO4-treated rats as compared with the untreated control group. The effects induced by either DON or PTX on most studied parameters were comparable. Combined treatment of DON and PTX induced remarkable results compared with their individual use. However, more clinical and preclinical studies are still required to further confirm and prove the long-term efficacy of such combination.

Vitamin D alleviates cognitive dysfunction and brain damage induced by copper sulfate intake in experimental rats: focus on its combination with donepezil.

This study aimed to demonstrate the potential benefits of donepezil (DPZ) and vitamin D (Vit D) in combination to counteract the neurodegenerative disorders induced by CuSO4 intake in experimental rats. Neurodegeneration (Alzheimer-like) was induced in twenty-four male Wistar albino rats by CuSO4 supplement to drinking water (10 mg/L) for 14 weeks. AD rats were divided into four groups: untreated AD group (Cu-AD) and three treated AD groups; orally treated for 4 weeks with either DPZ (10 mg/kg/day), Vit D (500 IU/kg/day), or DPZ + Vit D starting from the 10th week of CuSO4 intake. Another six rats were used as normal control (NC) group. The hippocampal tissue content of ß-amyloid precursor protein cleaving enzyme 1 (BACE1), phosphorylated Tau (p-tau), clusterin (CLU), tumor necrosis factor-α (TNF-α), caspase-9 (CAS-9), Bax, and Bcl-2 and the cortical content of acetylcholine (Ach), acetylcholinesterase (AChE), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured. Cognitive function tests (Y-maze) and histopathology studies (hematoxylin and eosin and Congo red stains) and immunohistochemistry for neurofilament. Vit D supplementation alleviated CuSO4-induced memory deficits including significant reduction hippocampal BACE1, p-tau, CLU, CAS-9, Bax, and TNF-α and cortical AChE and MDA. Vit D remarkably increased cortical Ach, TAC, and hippocampal Bcl-2. It also improved neurobehavioral and histological abnormalities. The effects attained by Vit D treatment were better than those attained by DPZ. Furthermore, Vit D boosted the therapeutic potential of DPZ in almost all AD associated behavioral and pathological changes. Vit D is suggested as a potential therapy to retard neurodegeneration.

Evaluation of clinical outcomes and efficacy of palonosetron and granisetron in combination with dexamethasone in Egyptian patients receiving highly emetogenic chemotherapy.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is considered one of the most serious adverse events affecting chemotherapy-receiving cancer patients. It dramatically affects their food intake, nutritional status and more importantly their quality of life. We can observe CINV in highly emetogenic chemotherapy (HEC) such as adriamycin-cyclophosphamide combination (AC) in breast cancer patients and cisplatin-based regimens in other cancer types. This study aimed to evaluate the antiemetic efficacy of palonosetron (PALO) over granisetron (GRA) in combination with dexamethasone for multiple highly emetogenic chemotherapy drugs (HEC), especially in chemotherapy regimens in Egyptian breast cancer patients and cisplatin-based regimens in other diseases. PATIENTS AND METHODS: An open-label randomized trial was carried out, including 115 patients receiving at least four cycles of highly emetogenic chemotherapy regimens. All patients received dexamethasone in combination with the 5-HT3 receptor antagonist. We recorded patients' clinical and biochemical characteristics and withdraw blood samples to monitor serum substance P and serotonin in correlation with chemotherapy-induced nausea and vomiting (CINV). We use the MASCC antiemetic tool in the acute phase (0-24 hr) and delayed phase (24-120 h) to evaluate patient outcomes in both stages after each chemotherapy cycle. RESULTS: In (PALO) group, only 7.84% of patients showed acute vomiting, and 11.76% showed acute nausea, whereas 43.75% of patients showed acute vomiting and 89.06% showed acute nausea in (GRA) group (P < 0.0001). For delayed CINV, 23.53% of patients showed delayed vomiting, and 47.06% showed delayed nausea in the (PALO) group, while 82.81% of patients showed delayed emesis, and 92.19% showed delayed nausea in (GRA) group (P < 0.0001). The study showed that PALO is a cost-effective choice when compared to GRA in CINV prevention as 45.10% of patients in (PALO) required additional rescue medications (Domperidone 10 mg orally three times per day plus Trimebutine 200 mg orally three times per week both for 5 days), while 95.24% in the (GRA) group used the same medications. Adverse events of both antiemetic drugs (PALO and GRA) include headaches and constipation and QTc prolongation reports, mostly mild to moderate, with relatively low rates among the two groups. CONCLUSION: Palonosetron, combined with dexamethasone, is more effective than granisetron and dexamethasone combination against both acute and delayed emesis induced by highly emetogenic chemotherapy (HEC) cisplatin-based protocols and the combination of cyclophosphamide and anthracyclines (AC). Medical team members should make more efforts, especially clinical pharmacy personnel, to monitor medications' effectiveness and help the medical team achieve a suitable and reliable care plan.

Relação da satisfação dos familiares com os cuidados prestados em unidades de terapia intensiva: desfechos de qualidade em hospitais sauditas acreditados / Relating family satisfaction to the care provided in intensive care units: quality outcomes in Saudi accredited hospitals

RESUMO Objetivo: Identificar os níveis de satisfação dos familiares de pacientes internados em unidades de terapia intensiva. Métodos: Este foi um estudo analítico transversal. As unidades gerais de terapia intensiva oferecem uma variedade de serviços a pacientes clínicos e cirúrgicos. Para as finalidades deste estudo, um entrevistador treinado fez contato com familiares dos pacientes, antes ou após o horário de visita. Resultados: O estudo incluiu 208 participantes, sendo 119 (57,2%) do sexo masculino. Dentre os pacientes, 73 (35,1%) se encontravam em um hospital particular e 135 (64,9%) em um hospital público na cidade de Al Madinah Al-Munawarah. Todos os participantes eram membros da família ou amigos de pacientes admitidos às unidades de terapia intensiva dos hospitais. As respostas de ambos os grupos proporcionaram escores baixos nos índices de satisfação. Observou-se, porém, um escore relativamente elevado nas respostas às questões 2, 6 e 10, concernentes, respectivamente, aos cuidados proporcionados pela equipe do hospital a seus pacientes, à atitude de cortesia dos membros da equipe das unidades de terapia intensiva para com os pacientes, e à satisfação dos pacientes com os cuidados médicos proporcionados. O escore foi muito baixo para o item 11, relacionado à possibilidade de melhorias nos cuidados médicos que os pacientes recebiam. Em geral foi relatada uma satisfação maior com os serviços oferecidos pelas unidades de terapia intensiva dos hospitais públicos, em comparação com a satisfação com os cuidados oferecidos pelas unidades de terapia intensiva dos hospitais privados. Conclusão: Em geral, foi obtido um escore baixo nos índices de satisfação, recomendando-se a realização de outros estudos para avaliar a situação atual, e melhorar a satisfação e a qualidade dos serviços fornecidos pelas unidades de terapia intensiva.

ABSTRACT Objectives: This study aims to identify the satisfaction levels of the family members of patients in intensive care units. Methods: This is a cross-sectional analytical study. General intensive care units offer a variety of services to clinical and surgical patients. For the purpose of this study, a trained interviewer communicated with the families of patients, either before or after visiting hours. Results: The study included 208 participants: 119 (57.2%) males and 89 (42.8%) females. Seventy-three (35.1%) of the patients attended a private hospital, and 135 (64.9%) attended a public hospital in the city of Al Madinah Al- Munawarah. All of the participants were either family members or friends of patients admitted to the intensive care units at the hospitals. The responses of both groups yielded low scores on the satisfaction index. However, a relatively high score was noted in response to questions 2, 6, and 10, which concerned the care that was extended by the hospital staff to their patients, the courteous attitude of intensive care unit staff members towards patients, and patients' satisfaction with the medical care provided, respectively. A very low score was obtained for item 11, which was related to the possibility for improvements to the medical care that the patients received. Overall, greater satisfaction with the services offered by the public intensive care units was reported compared to the satisfaction with the services offered by the private intensive care units. Conclusion: An overall low score on the satisfaction index was obtained, and further studies are recommended to assess the current situation and improve the satisfaction and quality of care provided by intensive care units.

High-performance liquid chromatography with diode array detection method for the simultaneous determination of seven selected phosphodiesterase-5 inhibitors and serotonin reuptake inhibitors used as male sexual enhancers.

This work presents a simple, sensitive and generic high-performance liquid chromatography with diode array detection method for the simultaneous determination of seven drugs prescribed for the treatment of erectile dysfunction and premature ejaculation. Investigated drugs include the phosphodiesterase-5 inhibitors: sildenafil, tadalafil, and vardenafil, in addition to the selective serotonin reuptake inhibitors: dapoxetine, duloxetine, fluoxetine, and paroxetine. The drugs were separated using a Waters C8 column (4.6 × 250 mm, 5 µm) with the mobile phase consisting of phosphate buffer pH 3, acetonitrile and methanol in the ratio 60:33:7. The flow rate was 1.2 mL/min, and quantification was based on measuring peak areas at 225 nm. Peaks were perfectly resolved with retention times 3.3, 3.9, 6.4, 7.5, 9.5, 10.7, and 13.4 min for vardenafil, sildenafil, paroxetine, duloxetine, dapoxetine, fluoxetine, and tadalafil, respectively. The developed method was validated with respect to system suitability, linearity, ranges, accuracy, precision, robustness, and limits of detection and quantification. The proposed method showed good linearity in the ranges 5-500, 2-200, 2-200, 3-300, 1.5-150, 2-200, and 2-200 µg/mL for sildenafil, tadalafil, vardenafil, dapoxetine, duloxetine fluoxetine, and paroxetine, respectively. The limits of detection were 0.18-0.38 µg/mL for the analyzed compounds. The applicability of the proposed method to real life situations was assessed through the analysis of commercial tablets, and satisfactory results were obtained.

Validated spectrofluorimetric determination of two pharmaceutical antihypertensive mixtures containing amlodipine besylate together with either candesartan cilexetil or telmisartan.

Amlodipine besylate (AML) is available in fixed-dose combination tablets with either candesartan cilexetil (CAN) or telmisartan (TEL). This work describes a simple, selective and sensitive spectrofluorimetric method for analysis of AML/CAN and AML/TEL binary mixtures without prior separation. The method involves measurement of the native fluorescence of AML at excitation and emission wavelengths of 367 and 454 nm, respectively, in water without interference from either of the two drugs. By contrast, the intrinsic fluorescence of CAN was measured at excitation and emission wavelengths of 265 and 392 nm, respectively, in ethanol, while TEL was measured at 366 nm in 0.05 M sodium hydroxide solution using 294 nm as the excitation wavelength. The proposed spectrofluorimetric procedure was validated with respect to linearity, ranges, precision, accuracy, selectivity, robustness, detection and quantification limits. Regression analysis showed a good correlation between fluorescence intensity and concentration over the ranges 0.1-1.4, 0.025-0.25 and 0.0025-0.05 µg/mL for AML, CAN and TEL, respectively. Limits of detection were 0.034, 0.0063 and 0.0007 µg/mL for AML, CAN and TEL, respectively. The proposed method was successfully applied for the analysis of several synthetic binary mixtures of different ratios and laboratory-prepared tablets with good recoveries, and no interference from common pharmaceutical additives was observed.

Distraction osteogenesis as followed by CT scan in Pierre Robin sequence.

THE AIM: The aim of this work was to assess the multislice CT scan for analysis of the craniofacial anatomic changes in Pierre Robin sequence both predistraction and postdistraction, and to assess the use of unidirectional internal distractors in this patient group. PATIENTS & METHODS: The study involved 11 patients. Their age at the time of distraction ranged from 2 to 7 months. Six were females and 5 were males. All had retromicrognathia, glossoptosis and obstructive sleep apnoea. All were diagnosed clinically and by CT scan. All were managed by distraction osteogenesis and were followed postoperatively by multislice CT. RESULTS: The distance between the base of the tongue and the posterior pharyngeal wall increased by a mean of 141%, and the total mandibular length increased by a mean of 26%. The increase in the distance between the hyoid bone and the posterior pharyngeal wall increased by a mean of 42% .The distance between the hyoid bone and the genoid process increased by a mean of 9%. CONCLUSION: Multislice CT scan was found to be a practical imaging technique to evaluate the morphologic changes in the airway and the mandible after distraction osteogenesis. It rules out the need for other traditional methods. Owing to the plasticity and malleability of the infant mandible that allow for sufficient bone remodelling, unidirectional internal distractors achieved a satisfactory maxillomandibular relationship which was tolerated by the infants and accepted by the parents.