The Genetic Basis of Moyamoya Disease.

Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive spontaneous bilateral occlusion of the intracranial internal cerebral arteries (ICA) and their major branches with compensatory capillary collaterals resembling a "puff of smoke" (Japanese: Moyamoya) on cerebral angiography. These pathological alterations of the vessels are called Moyamoya arteriopathy or vasculopathy and a further distinction is made between primary and secondary MMD. Clinical presentation depends on age and population, with hemorrhage and ischemic infarcts in particular leading to severe neurological dysfunction or even death. Although the diagnostic suspicion can be posed by MRA or CTA, cerebral angiography is mandatory for diagnostic confirmation. Since no therapy to limit the stenotic lesions or the development of a collateral network is available, the only treatment established so far is surgical revascularization. The pathophysiology still remains unknown. Due to the early age of onset, familial cases and the variable incidence rate between different ethnic groups, the focus was put on genetic aspects early on. Several genetic risk loci as well as individual risk genes have been reported; however, few of them could be replicated in independent series. Linkage studies revealed linkage to the 17q25 locus. Multiple studies on the association of SNPs and MMD have been conducted, mainly focussing on the endothelium, smooth muscle cells, cytokines and growth factors. A variant of the RNF213 gene was shown to be strongly associated with MMD with a founder effect in the East Asian population. Although it is unknown how mutations in the RNF213 gene, encoding for a ubiquitously expressed 591 kDa cytosolic protein, lead to clinical features of MMD, RNF213 has been confirmed as a susceptibility gene in several studies with a gene dosage-dependent clinical phenotype, allowing preventive screening and possibly the  development of new therapeutic approaches. This review focuses on the genetic basis of primary MMD only.

Clinical Evaluation of the Safety and Effectiveness of Heptonica: A Ghanaian Hepatorestorative Polyherbal Product.

The incidence of liver diseases is increasing globally, and many patients in developing countries are resorting to the use of herbal products as treatment. This study was aimed at establishing the safety and effectiveness outcomes for patients with deranged liver panel treated with a Ghanaian finished polyherbal product. The product Heptonica is prepared by CPMR from three medicinal plants: Bidens pilosa, Citrus aurantifolia, and Trema orientalis. Fifty (50) participants with clinical and biochemical signs of liver impairment were purposively recruited and treated for a period of 28 days. Participants received Heptonica at a dose of 30 mL 8 hourly after meals for the treatment period. Clinical and biochemical evaluation (liver panel test, renal function test, haematology, and urinalysis) of subjects for the safety and effectiveness of the product was undertaken at days 0 (baseline), 14, and 28. Compared to the baseline values, Heptonica did not have any untoward effect on renal function, haematological parameters, and urine parameters of subjects. Clinical and liver panel results of the participants also improved compared to the baseline: serum aspartate transaminase (AST) (p < 0.0001), alanine transaminase (ALT) (p < 0.0001), gamma-glutamyltransferase (GGT) (p- 0.0013), total bilirubin (p-0.0136), direct bilirubin (p < 0.0001), total proteins (p-0.0409), and alkaline phosphates (p- 0.0284). Level of albumin showed no significant difference within the study period. The outcome of this study indicates Heptonica has hepatorestorative action with no observable toxicity and can be used with confidence as indicated as a liver tonic.

Castor oil: a suitable green source of capping agent for nanoparticle syntheses and facile surface functionalization.

Castor oil (CO) is an inedible vegetable oil (VO) that has been employed extensively as a bioresource material for the synthesis of biodegradable polymers, cosmetics, lubricants, biofuels, coatings and adhesives. It is used in medicine, pharmaceuticals and biorefineries, due to its versatile chemistry. However, there has been less focus on CO as an alternative to toxic and expensive solvents, and capping/stabilizing agents routinely used in nanoparticle syntheses. It provides a richer chemistry than edible VOs as a solvent for green syntheses of nanoparticles. CO, being the only rich source of ricinoleic acid (RA), has been used as a solvent, co-solvent, stabilizing agent and polyol for the formation of polymer-nanoparticle composites. RA is a suitable alternative to oleic acid used as a capping and/or stabilizing agent. Unlike oleic acid, it provides a facile route to the functionalization of surfaces of nanoparticles and the coating of nanoparticles with polymers. For applications requiring more polar organic solvents, RA is more preferred than oleic acid. In this review, we discuss the production, chemical and physical properties, triglyceride and fatty acid (FA) compositions and applications of CO, focusing on the use of CO and RA as well as other VOs and FAs in syntheses of nanoparticles and surface functionalization.

Mir-660 is downregulated in lung cancer patients and its replacement inhibits lung tumorigenesis by targeting MDM2-p53 interaction.

Lung cancer represents the leading cause of cancer-related death in developed countries. Despite the advances in diagnostic and therapeutic techniques, the 5-year survival rate remains low. The research for novel therapies directed to biological targets has modified the therapeutic approach, but the frequent engagement of resistance mechanisms and the substantial costs, limit the ability to reduce lung cancer mortality. MicroRNAs (miRNAs) are small noncoding RNAs with known regulatory functions in cancer initiation and progression. In this study we found that mir-660 expression is downregulated in lung tumors compared with adjacent normal tissues and in plasma samples of lung cancer patients with poor prognosis, suggesting a potential functional role of this miRNA in lung tumorigenesis. Transient and stable overexpression of mir-660 using miRNA mimics reduced migration, invasion, and proliferation properties and increased apoptosis in p53 wild-type lung cancer cells (NCI-H460, LT73, and A549). Furthermore, stable overexpression using lentiviral vectors in NCI-H460 and A549 cells inhibited tumor xenograft growth in immunodeficient mice (95 and 50% reduction compared with control, respectively), whereas the effects of mir-660 overexpression were absent in H1299, a lung cancer cell line lacking p53 locus, both in in vitro and in vivo assays. We identified and validated mouse double minute 2 (MDM2) gene, a key regulator of the expression and function of p53, as a new direct target of mir-660. In addition, mir-660 expression reduced both mRNA and protein expression of MDM2 in all cell lines and stabilized p53 protein levels resulting in an upregulation of p21(WAF1/CIP1) in p53 wild-type cells. Our finding supports that mir-660 acts as a tumor suppressor miRNA and we suggest the replacement of mir-660 as a new therapeutic approach for p53 wild-type lung cancer treatment.

Phenotypic expression of the 3120+1G>A mutation in non-Caucasian children with cystic fibrosis in South Africa.

INTRODUCTION: Cystic fibrosis (CF) is the most common genetic disorder in Caucasians. Presentation of CF in non-Caucasians is less well studied. OBJECTIVE: This audit was undertaken to determine the phenotypic expression of the 3120+1G>A mutation in black and mixed race children in South Africa. METHODS: A multi-centre retrospective chart review of clinical, laboratory and spirometry data of non-Caucasian CF patients in four CF centres in South Africa was collected. Data was collected at diagnosis and after a five-year follow-up period. Ethical approval was granted for the study. RESULTS: A total of 30 participants were enrolled of whom 14 (47%) were homozygous and 16 (53%) heterozygous for the 3120+1G>A mutation. The mean age of diagnosis was 13 months. Twenty-four (80%) patients had malnutrition (mean weight z-score -3.6) or failure to thrive (77%) at presentation. Twenty (67%) presented with non-specific abdominal symptoms, whilst fifteen (50%) had recurrent respiratory tract infections. Pseudomonas aeruginosa was detected at a mean age of 21 months. The mean FEV1 was 73% predicted (95% CI 54.0-91.1) at study entry and 68% predicted (95% CI 49.74-87.06) at follow-up. CONCLUSION: Failure to thrive and a diagnosis of protein energy malnutrition (kwashiorkor) are the common presenting features of CF in children with the 3120+1G>A mutation. Meconium ileus is a rare presenting feature of CF in black and mixed race children with this deletion in South Africa.

Assesssing herbal medical practitioners in professional qualifying examination in Ghana, a model.

About 70% of Ghanaians depend on Alternative health practice for their primary health care needs. Hence, there is the need to streamline and regulate these practices. Graduates from the Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology (K.N.U.S.T), Kumasi-Ghana were assessed by the Professional Qualifying Examination Board of the Traditional Medicine Practice Council (TMPC), Ghana, after two years of internship training. A model of assessment took into consideration, the scope of the university training, internship and the primary health care needs of the society.

"The VIHsibilite Project": HIV-positive people in the Quebec press and community responses.

The VIHsibilite Project is a community-based action-research initiative that examines newspaper coverage of HIV/AIDS issues in Quebec from 1988 to 2004. Using standard qualitative research methods, and in consultation with an advisory committee of people directly impacted by HIV/AIDS news coverage, the project discerns trends in reporting on HIV/AIDS and undertakes discursive content analysis of these, aiming to better understand in what normative ways seropositive people are represented in print media, and, ultimately, to reduce the stigma attendant upon HIV infection. Preliminary findings include indications that seropositive women tend to be represented markedly differently from men in the news.

Antimicrobial activity of essential oils of Xylopia aethiopica.

Xylopia aethiopica is a medicinal plant of great repute in West Africa which produces a variety of complex chemical compounds. The fresh and dried fruits, leaf, stem bark and root bark essential oils showed various degrees of activity against the gram positive bacteria, Bacillus subtilis and Staphylococcus aureus, the gram negative bacteria Pseudomonas aeruginosa and the yeast-like fungus Candida albicans, using the cup plate method. However, none of the oils showed activity against Escherichia coli.

Evaluation of the antioxidant and free radical scavenging properties of Secamone afzelii Rhoem.

The antioxidant activity of a methanol extract of Secamone afzelii stems was tested using the DPPH assay and the active compound was identified as alpha-tocopherol. HPLC determination showed that 0.12% w/w alpha-tocopherol was present in the plant. The total extract also showed effective free radical scavenging activity in the assay for non-enzymatic lipid peroxidation in liposomes with an IC50 value of 90 microg/mL, with alpha-tocopherol isolated from the plant having an IC50 of 15 microg/mL in the same system, thus demonstrating the presence of other antioxidants.

Ethno-Botanical Survey Of Medicinal Plants In The Plant Genetic Resources Centre Arboretum - Bunso

The ethnobotanical uses and mode of administration of twenty-nine medicinal plants; found in the arboretum of the Plant Genetic Resource Centre located at Bunso in the eastern region of Ghana; against some disease conditions are hereby documented

Antimicrobial activity of the leaves and seeds of Bixa orellana.

The ethanolic extracts of the leaves and seeds of Bixa orellana showed a broad spectrum of antimicrobial activity. The activity of the leaf extract was more pronounced.

Dialyzer reuse impact on dialyzer efficiency, patient morbidity and mortality and cost effectiveness.

Since the introduction of dialyzer reuse more than three decades ago, several studies have reported its safety, efficacy and cost effectiveness. Reuse of hemodialyzer was prospectively studied in ten chronic hemodialysis (HD) patients recruited from the renal unit, the King Khalid University Hospital, Riyadh, Saudi Arabia, for three months. During the study period, 66 dialyzers were used for 408 sessions of HD, with a mean reuse of 6.2 +/- 5.3 episodes per dialyser, the mean of maximum reuse episodes being 13.7 +/- 8.0. The urea reduction ratio was maintained between 73 +/- 5% at baseline to 71.2 +/- 9.03% (p=0.53) at the maximum reuse. Similarly phosphate reduction with each HD session was maintained; mean decrease in phosphate levels was 0.67 mmol/L. Significant increase in heparin requirement was noted; however, the risk of bleeding was not increased. Hematocrit levels increased from 30.4 +/- 4.1% to 33.2 +/- 3.6% at the end of the study (p=0.6). Albumin leak in dialysate decreased with each reuse; baseline 8.27 +/- 7.93 mg/L to 2.8 +/- 0.4 mg/L at maximum reuse (p=0.04). Serum albumin levels remained stable. No short-term adverse effects on patients' morbidity and mortality were noted. Total cost savings of 53% was achieved with the reuse of dialyzers, excluding capital equipment used for preparation for reuse. In conclusion, dialyzer reuse seems to be safe and may provide an economical and efficient dialysis. Studies involving larger number of patients is required to validate this observation.

Phylogenetic analysis of human immunodeficiency virus 1 in Ghana.

Eleven human immunodeficiency virus 1 (HIV-1) isolates from Ghanaian acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) patients obtained by our serosurvey in 1986-1994 were genomically analyzed and phylogenetically compared with other known strains. A phylogenetic tree constructed by analyzing the env region indicated that heterogeneous HIV-1 strains were circulating in Ghana and the majority of them (9 of 11 isolates) belonged to clade (subtype) A which is now furiously epidemic in Africa. Another isolate (1 of 11) belonged to clade D, and the remaining one (1 of 11) belonged to "clade G". This "clade G" virus grouped by the env analysis belonged to clade A by its pol sequence, suggesting an A/G intersubtype recombinant. The characteristic sequences in the V3 tip which have not yet been reported were observed in these Ghanaian isolates, which should be taken into account for future vaccine programs.

PIP: The molecular epidemiology of HIV-1 in Ghana was investigated through genomic and phylogenetic analysis of isolates from 11 AIDS or AIDS-related complex patients obtained in 1986-94. A phylogenetic tree constructed by analyzing the env region indicated that heterogeneous HIV-1 strains are circulating in Ghana. 9 of the isolates belonged to clade A, 1 to subtype D, and 1 to "clade G"--an A/G intersubtype recombinant. The V3 loops of all isolates were composed of 35 amino acid residues--a characteristic not previously described. These molecular data on the genetic variability of the envelope glycoprotein of HIV-1 should be useful for future vaccine studies in West Africa.

Serological, virological, and polymerase chain reaction studies of HIV type 1 and HIV type 2 infections in Ghanaian patients with AIDS and AIDS-related complex.

We have used a particle agglutination (PA) test, Western blot (WB) test, polymerase chain reaction (PCR) test, and virus isolation to define the human immunodeficiency virus (HIV) status of 17 acquired immunodeficiency syndrome (AIDS), 6 AIDS-related complex (ARC), and 2 asymptomatic Ghanaians. HIV-1 antibodies were more frequently detected. The PCR detected 66.7% HIV-1, 11.1% HIV-2, and 5.6% of both HIV-1 and HIV-2 proviral DNA in peripheral blood mononuclear cell (PBMCs) and PBMC-Molt 4 coculture samples tested. Of the 12 viruses isolated from the 25 Ghanaians, 9 were HIV-1, 2 were HIV-2, and both HIV-1 and HIV-2 were isolated from 1 individual. Two of the HIV-1 isolates were from ARC patients who have been PA negative and either HIV-1 or HIV-2 WB indeterminate for more than 1 year without developing antibodies to HIV envelope proteins. Our results indicate that HIV-1 is now predominant in Ghanaian AIDS and ARC patients and that dual infection can occur.

PIP: While HIV is believed to be the causative agent for AIDS, many clinically diagnosed AIDS and AIDS-related complex (ARC) cases in Ghana have been reported to be negative or indeterminate for HIV antibodies. Dual seropositive reactions have also been common among AIDS and ARC cases in the country. A particle agglutination (PA) test, Western blot (WB), polymerase chain reaction (PCR), and virus isolation were used to define the HIV status of 17 AIDS, 6 ARC, and 2 asymptomatic Ghanaians. The PA test detected HIV-1 antibodies in 72% of the plasma samples, 94.4% of which were also positive according to WB. 1 sample was indeterminate by WB and 2 HIV-1 negative samples were determined to be positive by WB. HIV-2 was detected by PA in 32% of all samples, of which 87.5% were confirmed by WB. PCR detected 66.7% of HIV-1 cases, 11.1% of HIV-2, and 5.6% of both HIV-1 and HIV-2 proviral DNA in peripheral blood mononuclear cells (PBMCs) and PBMC-Molt 4 coculture samples tested. 12 viruses were isolated from the 25 subjects; 9 were identified as HIV-1, 2 as HIV-2, and 1 person was infected with both HIV-1 and HIV-2. 2 of the HIV-1 isolates were from ARC patients who had been PA-negative and either HIV-1 or HIV-2 WB indeterminate for more than 1 year without developing antibodies to HIV envelope proteins.