Nurul Izzah Ibrahim

Targeted delivery of lovastatin and tocotrienol to fracture site promotes fracture healing in osteoporosis model: micro-computed tomography and biomechanical evaluation.

Osteoporosis is becoming a major health problem that is associated with increased fracture risk. Previous studies have shown that osteoporosis could delay fracture healing. Although there are potential agents available to promote fracture healing of osteoporotic bone such as statins and tocotrienol, studies on direct delivery of these agents to the fracture site are limited. This study was designed to investigate the effects of two potential agents, lovastatin and tocotrienol using targeted drug delivery system on fracture healing of postmenopausal osteoporosis rats. The fracture healing was evaluated using micro CT and biomechanical parameters. Forty-eight Sprague-Dawley female rats were divided into 6 groups. The first group was sham-operated (SO), while the others were ovariectomized (OVx). After two months, the right tibiae of all rats were fractured at metaphysis region using pulsed ultrasound and were fixed with plates and screws. The SO and OVxC groups were given two single injections of lovastatin and tocotrienol carriers. The estrogen group (OVx+EST) was given daily oral gavages of Premarin (64.5 µg/kg). The Lovastatin treatment group (OVx+Lov) was given a single injection of 750 µg/kg lovastatin particles. The tocotrienol group (OVx+TT) was given a single injection of 60 mg/kg tocotrienol particles. The combination treatment group (OVx+Lov+TT) was given two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks of treatment, the fractured tibiae were dissected out for micro-CT and biomechanical assessments. The combined treatment group (OVx+Lov+TT) showed significantly higher callus volume and callus strength than the OVxC group (p<0.05). Both the OVx+Lov and OVx+TT groups showed significantly higher callus strength than the OVxC group (p<0.05), but not for callus volume. In conclusion, combined lovastatin and tocotrienol may promote better fracture healing of osteoporotic bone.

Update on Statins: Hope for Osteoporotic Fracture Healing Treatment

Fracture healing is a process of recovering injured bone tissue forms and functions. Osteoporosis can delay the healing process, which contributes to personal suffering and loss of activities. Osteoporosis patients tend to lose bone mass at the metaphyseal region which require treatment to increase bone mass. Postmenopausal osteoporosis is the most common osteoporosis that occurs in women which subsequently resulted in fractures even under slight trauma. Estrogen Replacement Therapy (ERT), the recommended therapy for postmenopausal osteoporosis, is associated with higher risk of breast cancer, ovarian cancer and cardiovascular diseases. As osteoporotic fractures are becoming a public health issue, alternative treatment is now being thoroughly explored. The potential agent is statins, the HMG-CoA reductase inhibitor which is widely used for hypercholesterolemia treatment. Statins have been found to increase bone mass by stimulation of Bone morphogenetic protein-2 (BMP-2) expression and Vascular Endothelial Growth Factor (VEGF) production. However, these bone forming effects were achieved at very high systemic doses. Therefore, studies on locally applied statins are required to further explore the ability of statins to stimulate bone formation at acceptable doses for better fracture healing. This review highlights the animal and clinical studies on fracture healing promotions by statins and the mechanisms involved.

Experimental fracture protocols in assessments of potential agents for osteoporotic fracture healing using rodent models

Osteoporosis may cause bone fracture even under slight trauma. Osteoporotic fracture has become a major public health problem but until today, the treatments available are not satisfactory. Many pre-clinical testings on animals were done to find new agents that can be sourced from natural products and synthetic drugs for osteoporotic fracture healing. Animal models are more appropriate for fracture healing study than human subject due to several reasons including the ethical issues involved. The bones of rodents are similar to human in term of their morphological change and response to therapy. Small rodents such as rats and mice are suitable animal models for fracture healing studies as they have a similar bone remodeling system to human. To date, there is no specific guideline to carry out fracture healing studies in animal models for the evaluation of new agents. This paper highlights the protocols of various fracture and fixation methods for experimental osteoporotic fracture healing using rodent models.

Drug delivery systems for prevention and treatment of osteoporotic fracture.

Anti-osteoporotic drugs are available for treatment of osteoporosis and for preventing osteoporosis complications especially fractures. Most of the current anti-osteoporotic drugs are administered orally or parenterally to target the osteoporosis-affected bones. However, bone is a peripheral organ with limited blood supply. Therefore, the drugs delivered are exposed to various physicochemical and biological factors which affect the bioavailability of the drugs. In preclinical research, the dose of a potential anti-osteoporotic agent used in animal model may be too high for human application when administered via the conventional route of administration. The current anti-osteoporotic drugs need to be administered at higher doses to account for pharmacological interactions. However, this will expose the patients to adverse effects such as the cancer risks of postmenopausal women who took estrogen replacement therapy. There is also problem with patient compliance as anti-osteoporotic drugs may have to be taken for prolonged duration. The current deliveries of drugs need to be improved to overcome these problems. This review discussed several potential drug delivery systems which are able to contain the anti-osteoporosis drugs and release them slowly to the targeted bone. Among them are various carriers, polymers and microsponges, which may not only increase drug efficacy but also reduce adverse effects. The delivery systems allow the drugs to be administered locally at the targeted bone for longer duration, therefore reducing drug frequency and improving patients compliance. It is hoped that these delivery systems may be applicable for the treatment of osteoporosis in the future to keep tab of the rising osteoporotic fracture incidence.

The Effects of Targeted Deliveries of Lovastatin and Tocotrienol on Ossification-Related Gene Expressions in Fracture Healing in an Osteoporosis Rat Model.

Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II–VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 µg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 µg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing.

Wound Healing Properties of Selected Natural Products

Wound healing is a complex process of recovering the forms and functions of injured tissues. The process is tightly regulated by multiple growth factors and cytokines released at the wound site. Any alterations that disrupt the healing processes would worsen the tissue damage and prolong repair process. Various conditions may contribute to impaired wound healing, including infections, underlying diseases and medications. Numerous studies on the potential of natural products with anti-inflammatory, antioxidant, antibacterial and pro-collagen synthesis properties as wound healing agents have been performed. Their medicinal properties can be contributed by the content of bioactive phytochemical constituents such as alkaloids, essential oils, flavonoids, tannins, saponins, and phenolic compounds in the natural products. This review highlights the in vitro, in vivo and clinical studies on wound healing promotions by the selected natural products and the mechanisms involved.

Activities of Daily Living and Determinant Factors among Older Adult Subjects with Lower Body Fracture after Discharge from Hospital: A Prospective Study

Fracture is a type of musculoskeletal injury that contributes to an inability to perform daily activities. The objective of this study was to evaluate activities of daily living (ADL) of older adult patients with lower body fracture and to determine factors influencing ADL. Patient’s ADL was assessed at pre-fracture, ward admission and post-discharge phases using the Katz ADL questionnaire. There were 129 subjects at pre-fracture and ward phases and 89 subjects at discharge phase. There were four independent variables; age, gender, type of fracture and ability to walk before fracture. Logistic regression models showed that ‘age’ and ‘ability to walk before fracture’ were the determinant factors of dependent for ‘bathing’, ‘dressing’ and ‘toileting’. The ‘ability to walk before fracture’ was the determinant factor of dependent for ‘transferring’. ‘Age’ and ‘gender’ were the determinant factors of dependent for ‘continence’, while ‘age’ was the determinant factor of dependent for ‘feeding’. The ADL score changes were significant across the phases with a reduction in ADL score in the ward admission phase and partial increment during the post-discharge phase. There were improvements in the health outcomes of subjects aged more than 50 years old after 3 months of being discharged from the hospital. In conclusion, age, being female, having a hip fracture and using a walking aid before fracture were the determinants identified in this study.

The Effects and Action Mechanisms of Phytoestrogens on Vasomotor Symptoms During Menopausal Transition: Thermoregulatory Mechanism

BACKGROUND Phytoestrogens have recently been claimed to positively influence menopausal discomforts, including hot flashes. However, little is known about the influence of phytoestrogens on core body temperature during oestrogen fluctuation at menopause. OBJECTIVE Previously published findings showed that phytoestrogens could relieve menopausal complaints, thus, the present review was aimed at assessing the effects of phytoestrogens on thermoregulatory mechanism during menopausal transition. RESULTS The molecular mechanisms underlying hot flashes are complex. Oestrogen fluctuations cause hypothalamic thermoregulatory centre dysfunction, which leads to hot flashes during menopause. The phytoestrogens of interest, in relation to human health, include isoflavones, lignans, coumestans, and stilbenes, which are widely distributed in nature. The phytoestrogens are capable of reducing hot flashes via their oestrogen-like hormone actions. The potential effects of phytoestrogens on hot flashes and their molecular mechanisms of action on thermoregulatory centre are discussed in this review. CONCLUSION The effects of phytoestrogens on these mechanisms may help explain their beneficial effects in alleviating hot flashes and other menopausal discomforts.

Targeted deliveries of tocotrienol and statin accelerate healing of osteoporotic fracture

Background Because of its structure and complex manufacturing process, every biotherapeutic product (BTP; medicinal products made by or derived from living organisms and produced by biotechnology) adheres to stringent quality assurance and control requirements, in addition to extensive nonclinical and clinical study data. Similarly, copy products of original biotherapeutics (termed as “biosimilars”) are subjected to equally strict regulatory control. BTPs have been registered in Malaysia since the 1990s; however, registration of biosimilars started only in 2008.Introduction: Anaphylaxis is a serious, rapid and potentially life-threatening allergic response involving IgE or IgG. Clinacanthus nutans, a small native shrub found in tropical Asia possess analgesic, anti-inflammatory and anti-viral activities and traditionally used for skin rashes, insect and snake-bites. In Thailand, alcoholic C. nutans extracts has been used topically for skin rashes, a symptom of allergy. Aim: To justify that C. nutans can treat skin rashes; this study investigated the anti-allergenicity of C. nutans extracts. Methods: Cytotoxicity of C. nutans extracts was evaluated by MTT on RBL-2H3. The most active C. nutans extract was determined by IgE-mediated mast cell degranulation. Acute toxicity of C. nutans aqueous extract was evaluated using female Sprague Dawley rats at 5000 mg/kg. Anti-allergenicity of C. nutans aqueous extract was studied by IgE-mediated passive systemic anaphylaxis (PSA). The release of preformed mediator (β-hexosaminidase) as well as newly synthesized mediators (TNF-α, IL-4 and LTC4) was evaluated. Results: C. nutans extracts were not cytotoxic up to 1 mg/ml (ethanolic) and 6 mg/ml (aqueous). In vitro, C. nutans aqueous extract was able to inhibit the release of preformed mediators but not newly synthesized mediators at 5 mg/ml. The ethanolic extracts were not able to inhibit all mediators tested. At 5000 mg/kg, C. nutans aqueous extract was non-toxic to the rats; no significant difference observed haematologically and biochemically. In vivo, C. nutans aqueous extract did not inhibit mediators of IgE-mediated PSA at 500 mg/kg and 2000 mg/kg. Conclusion: C. nutans aqueous extract was most active but could not inhibit mediators of IgE-mediated PSA. As anaphylaxis could be mediated by IgE orIgG, we postulate that C. nutans aqueous extract may exhibit its anti-allergenicity in IgG-mediated pathway.Accelerating wound healing is now considered as a principle clinical treatment and increasing the quality and speed of healing which has always been emphasized by the scientists. Propolis and honey are natural bee products with wide range of biological and medicinal properties. This study was aimed to determine the synergistic effect of honey and propolis in wound healing of rat skin. A total of 75 Wistar rats weighing 200-250 gr were placed under general anesthesia and sterile conditions. Then a square shape wound with 1.5*1.5 mm dimension was made on the back of the neck. Animals were randomly divided into control, honey, propolis, combined honey propolis and phenytoin 1% groups, respectively. Rats were randomly divided into the following groups: 4th, 7th and, 14th days of treatment in each period of study. Wound area in the experimental group was covered once daily with a fixed amount of thyme honey, propolis, propolis and honey and phenytoin cream (1%), the control group did not receive any treatment. For histological studies, during the fourth, seventh and fourteenth days rats were sacrificed and samples were taken from the wound and adjacent skin. After histological staining fibroblast, neutrophils, macrophages and vascular sections were counted in the wound bed. The macroscopic and microscopic evaluations showed that the percentage of wound healing on different days in the experimental and control groups were significant (P<0.05). The macroscopic and microscopic evaluation showed that the percentage of wound healing on different days in combined propolis and honey experimental group was significantly different from the control group (Multivariate ANOVA test) (P<0.05). Combined application of propolis and honey on the open wound healing in rats has a synergistic effect.Children are more susceptible to medication errors than adults. Medication administration process is the last stage in the medication treatment process and most of the errors detected in this stage. Little research has been undertaken about medication errors in children in the Middle East countries. This study was aimed to evaluate how the paediatric nurses adhere to the medication administration policy and also to identify any medication preparation and administration errors or any risk factors. An observational, prospective study of medication administration process from when the nurses preparing patient medication until administration stage (May to August 2014) was conducted in Saudi Arabia. Twelve paediatric nurses serving 90 paediatric patients were observed. 456 drug administered doses were evaluated. Adherence rate was variable in 7 steps out of 16 steps. Patient allergy information, dose calculation, drug expiry date were the steps in medication administration with lowest adherence rates. 63 medication preparation and administration errors were identified with error rate 13.8% of medication administrations. No potentially life-threating errors were witnessed. Few logistic and administrative factors were reported. The results showed that the medication administration policy and procedure need an urgent revision to be more sensible for nurses in practice. Nurses’ knowledge and skills regarding to the medication administration process should be improved. Keywords—Double checking, Medication administration errors, Medication safety, Nurses.