Evaluation of metal nanoparticles for drug delivery systems

Diminazene aceturate is a trypanocide with unwanted toxicity and limited efficacy.It was reasoned that conjugating diminazene aceturate to functionalized nanoparticle would lower untoward toxicity while improving selectivity and therapeutic efficacy.Silver and gold nanoparticles were evaluated for their capacities to serve as carriers for diminazene aceturate.The silver and gold nanoparticles were synthesized,functionalized and coupled to diminazene aceturate following established protocols.The nanoparticle conjugates were characterized.The free diminazene aceturate and drug conjugated nanoparticles were subsequently evaluated for cytotoxicity in vitro.The characterizations by transmission electron microscopy or UV/Vis spectroscopy revealed that conjugation of diminazene aceturate to silver or gold nanoparticles was successful.Evaluation for cytotoxic actions in vitro demonstrated no significance difference between free diminazene aceturate and the conjugates.Our data suggest that surface modified metal nanoparticles could be optimized for drug delivery systems.     

Catecholaminergic neurons in the brain-stem and sleep apnea in SIDS victims

Background: Tyrosine hydroxylase (TH) is a specific marker for catecholaminergic neurones. Some reports have demonstrated a decrease of TH in the sudden infant death syndrome (SIDS) compared with controls. To further investigate this, the correlation between TH and sleep apnea was investigated here. Materials and methods: Among 27,000 infants studied prospectively to characterize their sleep–wake behavior, 38 infants died under 6 months of age. They included 26 cases of SIDS. All the infants had been recorded during one night in a pediatric sleep laboratory some 3–12 weeks before death. The frequency and the duration of sleep apnea were analyzed. The brain-stem material was collected and subjected to immunohistochemical studies for TH. The density of TH-immunoreactive neurons was measured in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguus and the ventrolateral medulla (VLM) in the medulla oblongata. Correlation analyses were carried out between the density of TH-immunoreactive neurons and the data from the sleep apnea studies. Results: There was no SIDS specific correlation between TH-immunoreactive neurons in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguus and the ventrolateral medulla in the medulla oblongata and the frequency and duration of sleep apnea. Conclusions: No significant association between the pathological data and the physiological data refers to TH-positive neurons in the medulla oblongata in SIDS victims.     

Correlation between the Ki-67 antigen in the brainstem and physiological data on sleep apnea in SIDS victims

Background: The Ki-67 antigen appears in all human proliferating cells during late G1, S, M and G2 phases of the cell cycle, but is consistently absent in the G_o phase (noncycling) cells. The correlation between Ki-67 in the brainstem and sleep apnea in victims of the sudden infant death syndrome (SIDS) was investigated to elucidate cell kinetics in the brainstem of this condition, which is still the main cause of postneonatal infant death. Materials and methods: Twenty-six cases of SIDS occurred among 38 infants dying under 6 months of age in a cohort of 27,000 infants studied prospectively to characterize their sleep–wake behavior. All the infants had been recorded during one night in a pediatric sleep laboratory some 3–12 weeks before death. The frequency and duration of sleep apnea were analyzed. At autopsy, brainstem material was collected and immunohistochemistry for Ki-67 was carried out. The density of Ki-67-positive neurons was measured semiquantitatively. Correlation analyses were carried out between the density of Ki-67-positive neurons and the data on sleep apnea. Results: Except in two cases in SIDS victims and in one control, the detection of Ki-67 was negative. No correlation analysis between the Ki-67 and of sleep apnea was found. Conclusions: There were no abnormal cell kinetics detected by the demonstration of Ki-67 antigen in the brainstems of SIDS victims.     

Growth of nerve fibres into murine peritoneal adhesions

Adhesions in the peritoneal cavity have been implicated in the cause of intestinal obstruction and infertility, but their role in the aetiology of chronic pelvic pain is unclear. Nerves have been demonstrated in human pelvic adhesions, but the presence of pain-conducting fibres has not been established. The purpose of this study was to use an animal model to examine the growth of nerves during adhesion formation at various times following injury and to characterize the types of fibres present. Adhesions were generated in mice by injuring the surface of the caecum and adjacent abdominal wall, with apposition. At 1-8 weeks post-surgery, adhesions were processed and nerve fibres characterized histologically, immunohistochemically, and ultrastructurally. Peritoneal adhesions had consistently formed by 1 week after surgery and from 2 weeks onwards, all adhesions contained some nerve fibres which were synaptophysin, calcitonin gene-related peptide, and substance P-immunoreactive, and were seen to originate from the caecum. By 4 weeks post-surgery, nerve fibres were found to originate from both the caecum and the abdominal wall, and as demonstrated by acetylcholinesterase histochemistry, many traversed the entire adhesion. Ultrastructural analysis showed both myelinated and non-myelinated nerve fibres within the adhesion. This study provides the first direct evidence for the growth of sensory nerve fibres within abdominal visceral adhesions in a murine model and suggests that there may be nerve fibres involved in the conduction of pain stimuli.     

Visualisation of uric acid renal calculi (UARC) using computed radiography (CR)

AimTo investigate the capability of CR to visualise UARC through inverse image post-processing technique.Methods. A patient-equivalent phantom (PEP) consisting of six 2.5-cm thick Perspex layers and one 1-mm thick aluminium layer was used to represent human tissues and bones respectively. A total of eight exposures were made on PEP to radiograph 1 mm, 2 mm and 3 mm UARC located between three layers of 2-cm thick cattle muscle, positioned inside the PEP. After each exposure, a layer of Perspex was removed, and another exposure was made until only one Perspex layer and one layer of muscle (containing the three UARC) remained. For each exposure, two images (a positive and an inverse image) were produced for comparison using Fuji XG1 computed radiography system with IP0 type C-ST-VI Fuji imaging plate (equivalent to 400 speed radiographic screen-film systems).ResultsIn positive image, UARC of all three sizes (1 mm, 2 mm and 3 mm) located in the cattle muscle, cannot be visualised when the PEP consists of more than one layer of Perspex. In inverse image, the 3-mm UARC can be seen even when the PEP consists of five layers of Perspex.ConclusionThis study revealed the post-processing capability of CR to increase the visualisation of UARC which has been categorised as radiolucent. A further study of clinical image quality should be performed using blinded observers to test diagnostic accuracy, which was not included in this study.     

Chemopreventive Efficacy of Ginger (Zingiber Officinale) in Ethionine Induced Rat Hepatocarcinogenesis

Ginger (Zingiber officinale Rosco) is widely used in foods as a spice all around the world. It has been reported to have antioxidant and anticarcinogenic properties. We investigated the effect of ginger in ethionine induced rat hepatocarcinogenesis. Male Wistar rats were divided into 5 groups: group 1 and 2 served as controls and they received normal rat chow and olive oil respectively. Group 3 was fed with ginger oleoresin dissolved in olive oil at 100 mg/kg body wt. Group 4 was fed with choline deficient diet and 0.1% ethionine in drinking water (CDE diet), and group 5 received ginger with CDE diet. Blood samples were taken from the orbital sinus at 0 and 8 weeks of experiment for the determination of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase and lipid peroxidation end product, malondialdehyde (MDA). Rats were also killed at 8 weeks for the observation of liver tumor formation. CDE diet induced the formation of liver nodules in rats and increased SOD activity. However, it had no effect on catalase, GPx and MDA levels when compared to both controls at 8 weeks of experiment. When CDE rats were treated with ginger, the formation of liver tumour, SOD activity and MDA level reduced, catalase activity was increased but no change was observed for GPx activity when compared to CDE group. In conclusion, ginger supplementation suppressed liver carcinogenesis by scavenging the free radical formation, and by reducing lipid peroxidation.     

Echocardiographic pattern and severity of valve dysfunction in children with rheumatic heart disease seen at Uganda Heart Institute,Mulago hospital

Background

Rheumatic heart disease (RHD) is the commonest acquired heart disease in children worldwide but in Uganda, data is scarce regarding its morbidity and mortality. The disease has a progressive course and patients usually require valve repair/replacement in the future.

Objectives

To describe the frequency of echocardiographic valvular dysfunction in children with RHDTo explore the relationship between the severity of valvular dysfunction by the age and sex of the children with RHD

Methods

Echocardiographic findings of children ≤15 years with RHD seen at Uganda Heart Institute from January 2007 to December 2011 were retrospectively analyzed.

Results

376 children had a diagnosis of RHD. The mean age of the children was 11.0±2.7 years and 216 (57.4%) were females. Mitral regurgitation was the commonest lesion seen in 98.9% (severe in 73.1%) of the children. Aortic regurgitation (AR) was found in 51.3% (severe in 7.2%), mitral stenosis (MS) was found in 10.6% (severe in 5.9%), tricuspid regurgitation was found in 86.7% (severe in 8.2%) while aortic stenosis was seen in 1.3% (severe in 0.3%). Severe AR was less common in females (OR=0.32, 95%CI 0.13–0.78) and children with MS were older than those without MS (12.7±2.0 Vs. 10.7±2.7 years, p<0.00).

Conclusions

Mitral valve dysfunction was found in almost all the cases of RHD and majority of the children had severe valve disease at the time of their first presentations. Children with MS were predominantly above 10 years and severe AR was more common in males.     

Waterborne parasites and physico-chemical assessment of selected lakes in Malaysia

The objective of this study was to assess the physico-chemical parameters and waterborne parasites in selected recreational lakes from Malaysia. Samples were collected from seven stations of Recreational Lake A (RL-A) and six stations of Recreational Lake B (RL-B). The samples were processed to detect the presence of Giardia spp. and Cryptosporidium spp. using immunomagnetic separation kit, helminth eggs or ova by bright field microscopy and Acanthamoeba spp. by cultivation in non-nutrient agar. Chemical parameters such as ammonia, chlorine, fluoride, nitrate and nitrite and physical parameters such as dissolved oxygen, electrical conductivity, pH, salinity, temperature and total dissolved solid were also measured. Both lakes were freshwater with salinity ranging from 0.05 to 0.09 ppt. Most stations of these lakes were contaminated with Cryptosporidium spp., Giardia spp., Ascaris spp. and hookworm. Schistosoma spp. was found in RL-B only, while Acanthamoeba spp. was found in all stations. Of all sampling sites, station 5 of RL-B is the most contaminated. Linear regression and correlation analysis revealed that Giardia spp. and Schistosoma spp. showed a significant negative correlation with turbidity (p?<?0.01). Based on the preliminary data obtained, it is clearly shown that there is a necessity to implement the detection of waterborne parasites and physico-chemical analysis in Malaysia. Future work on heavy metals (chromium, copper, mercury and zinc) is recommended to enhance the overall water quality monitoring and to take appropriate safety measures to ensure maintenance of good water standards.     

Phenotypic delineation of the retinal arterial macroaneurysms with supravalvular pulmonic stenosis syndrome

Retinal arterial macroaneurysms with supravalvular pulmonic stenosis (RAMSVPS), also known as Familial Retinal Arterial Macroaneurysms (FRAM) syndrome, is a very rare multisystem disorder. Here, we present a case series comprising ophthalmologic and systemic evaluation of patients homozygous for RAMSVPS syndrome causative IGFBP7 variant. New clinical details on 22 previously published and 8 previously unpublished patients are described. Age at first presentation ranged from 1 to 34 years. The classical feature of macroaneurysms and vascular beading involving the retinal arteries was universal. Follow up extending up to 14 years after initial diagnosis revealed recurrent episodes of bleeding and leakage from macroaneurysms in 55% and 59% of patients, respectively. The majority of patients who underwent echocardiography (18/23) showed evidence of heart involvement, most characteristically pulmonary (valvular or supravalvular) stenosis, often requiring surgical correction (12/18). Four patients died in the course of the study from complications of pulmonary stenosis, cerebral hemorrhage, and cardiac complications. Liver involvement (usually cirrhosis) was observed in eight patients. Cerebral vascular involvement was observed in one patient, and stroke was observed in two. We conclude that RAMSVPS is a recognizable syndrome characterized by a high burden of ocular and systemic morbidity, and risk of premature death. Recommendations are proposed for early detection and management of these complications.