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Fulltext Formulation and evaluation of galantamine gel as drug reservoir in transdermal patch delivery system

Fong Yen W, Basri M, Ahmad M, Ismail M

ScientificWorldJournal, 2015;2015:495271.
PMID: 25853145 DOI: 10.1155/2015/495271

Galantamine hydrobromide is formulated in tablets and capsules prescribed through oral delivery for the treatment of Alzheimer's disease. However, oral delivery of drugs can cause severe side effects such as nausea, vomiting, and gastrointestinal disturbance. Transdermal delivery of galantamine hydrobromide could avoid these unwanted side effects. In this work, galantamine hydrobromide was formulated in gel drug reservoir which was then fabricated in the transdermal patch. The in vitro drug release studies revealed that the drug release from the donor chamber to receptor chamber of Franz diffusion cell was affected by the amount of polymer, amount of neutralizer, amount of drug, types of permeation enhancer, and amount of permeation enhancer. Visual observations of the gels showed that all formulated gels are translucent, homogeneous, smooth, and stable. These gels have pH in the suitable range for skin. The gel also showed high drug content uniformity. Hence, this formulation can be further used in the preparation of transdermal patch drug delivery system.

Matched MeSH terms: Alzheimer Disease/drug therapy*
Fulltext Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer

Rebbeck TR, Mitra N, Wan F, Sinilnikova OM, Healey S, McGuffog L, et al.

JAMA, 2015 Apr 07;313(13):1347-61.
PMID: 25849179 DOI: 10.1001/jama.2014.5985

IMPORTANCE: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists.
OBJECTIVE: To identify mutation-specific cancer risks for carriers of BRCA1/2.
DESIGN, SETTING, AND PARTICIPANTS: Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk.
EXPOSURES: Mutations of BRCA1 or BRCA2.
MAIN OUTCOMES AND MEASURES: Breast and ovarian cancer risks.
RESULTS: Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% CI, 1.22-1.74; P = 2 × 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P = 6 × 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P = 9 × 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95% CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69-3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44-0.60; P = 6 × 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers.
CONCLUSIONS AND RELEVANCE: Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.

Matched MeSH terms: Genetic Predisposition to Disease*
Current advance methods for the identification of blast resistance genes in rice

Tanweer FA, Rafii MY, Sijam K, Rahim HA, Ahmed F, Latif MA

C. R. Biol., 2015 May;338(5):321-34.
PMID: 25843222 DOI: 10.1016/j.crvi.2015.03.001

Rice blast caused by Magnaporthe oryzae is one of the most devastating diseases of rice around the world and crop losses due to blast are considerably high. Many blast resistant rice varieties have been developed by classical plant breeding and adopted by farmers in various rice-growing countries. However, the variability in the pathogenicity of the blast fungus according to environment made blast disease a major concern for farmers, which remains a threat to the rice industry. With the utilization of molecular techniques, plant breeders have improved rice production systems and minimized yield losses. In this article, we have summarized the current advanced molecular techniques used for controlling blast disease. With the advent of new technologies like marker-assisted selection, molecular mapping, map-based cloning, marker-assisted backcrossing and allele mining, breeders have identified more than 100 Pi loci and 350 QTL in rice genome responsible for blast disease. These Pi genes and QTLs can be introgressed into a blast-susceptible cultivar through marker-assisted backcross breeding. These molecular techniques provide timesaving, environment friendly and labour-cost-saving ways to control blast disease. The knowledge of host-plant interactions in the frame of blast disease will lead to develop resistant varieties in the future.

Matched MeSH terms: Disease Resistance/genetics*
Fulltext Inhibitory and apoptosis-inducing effects of Newcastle disease virus strain AF2240 on mammary carcinoma cell line

Ahmad U, Ahmed I, Keong YY, Abd Manan N, Othman F

Biomed Res Int, 2015;2015:127828.
PMID: 25821783 DOI: 10.1155/2015/127828

Breast cancer is the malignant tumour that developed from cells of the breast and is the first leading cause of cancer death among women worldwide. Surgery, radiotherapy, and chemotherapy are the available treatments for breast cancer, but these were reported to have side effects. Newcastle disease virus (NDV) known as Avian paramyxovirus type-1 (APMV1) belongs to the genus Avulavirus in a family Paramyxoviridae. NDV is shown to be a promising anticancer agent, killing tumour cells while sparing normal cells unharmed. In this study, the oncolytic and cytotoxic activities of NDV AF2240 strain were evaluated on MDA-MB-231, human mammary carcinoma cell line, using MTT assay, and its inhibitory effects were further studied using proliferation and migration assays. Morphological and apoptotic-inducing effects of NDV on MD-MB-231 cells were observed using phase contrast and fluorescence microscopes. Detection of DNA fragmentation was done following terminal deoxyribonucleotide transferase-mediated Br-dUTP nick end labeling staining (TUNEL) assay, which confirmed that the mode of death was through apoptosis and was quantified by flow cytometry. Furthermore, analysis of cellular DNA content demonstrated that the virus caused an increase in the sub-G1 phase (apoptotic peak) of the cell cycle. It appears that NDV AF2240 strain is a potent anticancer agent that induced apoptosis in time-dependent manner.

Matched MeSH terms: Newcastle disease virus/physiology*
[Myocarditis caused by enteroviruses in Greece--and in Germany?]

Braun R, Hassler D, Kimmig P

Dtsch. Med. Wochenschr., 2002 Jun 21;127(25-26):1364.
PMID: 12136792
Matched MeSH terms: Disease Outbreaks*
Enterovirus 71: the virus, its infections and outbreaks

Ho M

J Microbiol Immunol Infect, 2000 Dec;33(4):205-16.
PMID: 11269363

Enterovirus 71 (EV71) was first recognized in 1974. Since then it has been implicated in 13 small and large outbreaks world-wide. Large outbreaks of hand, foot and mouth disease (HFMD), mostly benign, occurred in Japan in 1973 and 1978. Four outbreaks with brain stem encephalitis and significant numbers of deaths occurred in Bulgaria and Hungary in the late 1970's and in Malaysia and Taiwan in 1997 and 1998 respectively. During the latter two epidemics, pulmonary edema and hemorrhage often leading to quick deaths in children aged from 0.5 to 3 years old was first recognized. In Taiwan 78 deaths and over 100,000 cases of HFMD occurred. Coxsackie A16 cocirculated with EV 71, without however, causing any severe illnesses. The transmission of EV 71 was related to number of siblings in a household, rural residence and contact with cases of HFMD. Genotype analyses show that genotypes have changed with time in the United States and Japan. Recent isolates from Japan are similar to the isolates from Malaysia and Taiwan in 1997 and 1998, respectively. Even though genotype analysis has not identified specific sequences responsible for neurovirulence, the strains causing brain stem encephalitis and pulmonary edema in the Far East are similar and have arisen since 1997. Seroepidemiological studies in Taiwan suggest that children aged from 0.5 to 4 years old are most susceptible while the rest of the population are over 50% immune. Theoretically there is a pool of such susceptible subjects every few years. In prevention for another major outbreak, a simple, inactivated Salk type vaccine should be immediately prepared and made available.

Matched MeSH terms: Disease Outbreaks*
Mary Jane Cardosa--bringing local solutions to Sarawak, Malaysia

Cardosa MJ

Lancet Infect Dis, 2001 Sep;1(2):128-32.
PMID: 11871464
Matched MeSH terms: Disease Outbreaks*
Fulltext Prevalence of coronary risk factors in a sample of Chinese women in Kuala Lumpur

Khor GL, Hsu-Hage BH, Sundram K, Wahlqvist ML

Med J Malaysia, 1997 Dec;52(4):367-76.
PMID: 10968113

Several risk factors for cardiovascular disease amongst a sample of urban Chinese women were investigated. These factors included body mass index (BMI), waist hip ratio, total blood cholesterol (TC), HDL-cholesterol and Lp(a) levels, blood pressure, cigarette smoking, family history of chronic disease, dietary habits and frequency of selected food intake. The subjects were found to have coronary risks with respect to BMI and TC level, both of which increased with age of the women. Hypertension, HDL-cholesterol and Lp(a) levels appeared not to pose as risk factors amongst these subjects. Dietary habits and intake showed significant correlations with subjects' BMI status. Health promotion is called for towards reducing the modifiable coronary risk factors.

Matched MeSH terms: Coronary Disease/etiology*
Fulltext Health status of senior civil servants in Kuala Lumpur

Liew YM, Zulkifli A, Tan H, Ho YN, Khoo KL

Med J Malaysia, 1997 Dec;52(4):348-66.
PMID: 10968112

733 senior civil servants comprising 520 males and 213 females with a mean age of 44 years (range 25-56 years) were screened for their health status. The sample population comprised of 67.9% Malays, 22.5% Chinese, 9.1% Indians and 0.4% other ethnic origins. The subjects' medical histories were recorded and a full medical examination including anthropometric measurements (weight, height, waist and hip circumference), blood biochemistry and urine analysis, chest X-ray and electrocardiograms were done. The results obtained showed that 36.0% of the study population were overweight with 6.5% being obese. Of this 32.0% had central obesity. 15.2% of the subjects had systolic hypertension (systolic BP > or = 140 mmHg) whilst 27.6% had diastolic hypertension (diastolic BP > or = 90 mmHg). Hyperlipidaemia was common, with 75.2% subjects having raised cholesterol, 19.9% raised triglycerides, 50.2% raised LDL-C, 74.6% raised TC:HDL-C and 26.6% raised LDL:HDL-C. An elevated blood glucose was found in 8.4% subjects, whilst urine sugar was detected in only 2.6%, and a raised uric acid was found in 2.8% subjects. The prevalence of hypertension, raised blood glucose and hyperlipidaemia increased with age with more males affected than females. Although hypercholesterolaemia appeared more frequently amongst the Malays, the Indians, by comparison had the highest prevalence for a raised LDL:HDL-C ratio, a reflection of the increase in LDL-C and a concomitant decrease in HDL-C. The latter findings indicate that the Indians are at greater risk for the development of coronary heart disease than the Chinese and Malays. In addition, the mean levels of serum cholesterol found in this study seemed to have exceeded the levels found in populations in the industrialised countries such as the USA. There is thus an urgent need for more public health campaigns aimed at the reduction and control of such coronary risk factors.

Matched MeSH terms: Coronary Disease/etiology
Fulltext Guidelines in the management of chronic obstructive pulmonary disease. A consensus statement of the Ministry of Health of Malaysia, Academy of Medicine of Malaysia and Malaysian Thoracic Society

Med J Malaysia, 1999 Sep;54(3):387-401.
PMID: 11045071
Matched MeSH terms: Pulmonary Disease, Chronic Obstructive*
Molecular evidence of clonality amongst Vibrio cholerae O1 biotype El Tor during an outbreak in Malaysia

Vadivelu J, Iyer L, Kshatriya BM, Puthucheary SD

Epidemiol Infect, 2000 Feb;124(1):25-30.
PMID: 10722126

Forty-three clinical strains of V. cholerae O1 biotype E1 Tor were isolated between 3 May and 10 June 1998 during an outbreak in the metropolitan area of Kuala Lumpur and its suburbs. With the exception of three Inaba strains that were restricted to three members of a family, all the others belonged to the Ogawa serotype. The strains were analysed for clonality using ribotyping and pulsed-field gel electrophoresis (PFGE). Two ribotypes, V/B21a and B27, were identified among 40 Ogawa isolates using BglI restriction endonuclease. Ribotype V/B21a has been described previously from Taiwan and Colombia and several Asian countries while B27 has been reported among isolates from Senegal. The three Inaba strains belonged to one ribotype, designated type A, not previously reported. PFGE analysis using NotI revealed that all isolates within a ribotype had identical profiles demonstrating clonality amongst the strains. Dice coefficient analysis of the two Ogawa genotypes revealed 89% similarity on ribotype patterns and 91.3% on PFGE profiles. Ribotype V/B21a isolates were associated with cases from dispersed areas of Kuala Lumpur and its suburbs while ribotype B27 was restricted to cases from one particular area suggesting a common-source outbreak.

Matched MeSH terms: Disease Outbreaks*
HLA-DRB1 genes and susceptibility to rheumatoid arthritis in three ethnic groups from Malaysia

Kong KF, Yeap SS, Chow SK, Phipps ME

Autoimmunity, 2002 Jul;35(4):235-9.
PMID: 12482190

Worldwide population studies have generally agreed that rheumatoid arthritis (RA) is associated with a group of HLA-DRB1 alleles which share a common amino acid sequence at residues 70-74. This represents the first study to investigate the association of HLA-DRB1 genes with susceptibility to RA amongst Malay, Chinese and Indian ethnic groups in Malaysia. One hundred and thirty three RA patients and one hundred and sixty seven healthy controls were recruited. The HLA-DRB1 alleles were studied using the Phototyping method. The subtypes of HLA-DR4 were detected by "high resolution" PCR-SSP DRB1*04 typing techniques. The prevalence of HLA-DRB1*0405 was significantly higher in Malay patients with RA than in healthy controls (28.9 vs. 8.3%, p = 0.0016, OR = 4.48, 95% CI = 1.26-16.69). Similarly, DRB1*0405 was more common in Chinese RA patients than in controls (30.0 vs. 6.7%, p = 0.0029, OR = 6.00, 95% CI = 1.67-23.48). In addition, DRB1*0901 was a predisposing factor (32.0 vs. 6.7%,p = 0.0015, OR = 6.59, 95% CI = 1.85-25.64) and *0301/04 had a protective role (4.0vs. 25.0%, p = 0.00562, OR = 0.13, 95% CI = 0.02-0.62) in Malaysian Chinese RA. RA in Indians was associated with DRB1*1001 (51.1 vs. 8.5%,p = 0.00002, OR = 11.24, 95% CI = 3.13-44.18). DRB1*0701 (13.3 vs. 42.6%,p = 0.0022, OR = 2.73, 95% CI = 1.40-5.37) may have a protective effect. Therefore, in the Malaysian population, RA is primarily associated with the QRRAA motif, and we suggest that genetic factors play a crucial role in the pathogenesis of RA, compared to environmental factors.

Matched MeSH terms: Genetic Predisposition to Disease*
[Nipah virus outbreak in Malaysia, 1999]

Okabe N, Morita K

Uirusu, 2000 Jun;50(1):27-33.
PMID: 10998976
Matched MeSH terms: Disease Outbreaks*
Fulltext An outbreak of rabies in dogs in the state of Terengganu 1995-1996

Loke YK, Murugesan E, Suryati A, Tan MH

Med J Malaysia, 1998 Mar;53(1):97-100.
PMID: 10968145

The presence of rabies in dogs has been well recognized in areas of Malaysia close to the Thai border but it has rarely ever been reported in Terengganu which is a state on the East Coast of Malaysia. From November 1995 to June 1996 six different rabid stray dogs were found to have been involved in dog bite attacks on 9 members of the public. We report these cases to highlight that rabid dog bites may occur even in areas where the disease is thought to be rate. Medical and veterinary staff must keep the possibility of the risk of rabies in mind when faced with patients who have been bitten by dogs.

Matched MeSH terms: Disease Outbreaks*
Fulltext The prevalence of Chlamydia trachomatis in patients with pelvic inflammatory disease

Ravindran J, Tan YI, Ngeow YF

Med J Malaysia, 1998 Mar;53(1):16-21.
PMID: 10968132

Chlamydia trachomatis is recognized as the most prevalent sexually transmitted organism in many parts of the world. Most complications associated with chlamydial infection in women and their infants can be avoided by appropriate treatment. However, treatment is often not initiated because infections are frequently asymptomatic. The identification of at risk patients and treatment of these patients is a practical clinical approach in the reduction of transmission and prevention of complications. The prevalence of chlamydial infection among patients with pelvic inflammatory disease admitted to Seremban General Hospital was 22.7%. The difference in seropositivity between PID patients (20.5%) and antenatal controls (2.3%) was statistically significant. The corresponding cervical antigen detection rates were 6.8% and 2.3% respectively. Chlamydial infection should be screened for in gynaecological patients and antibiotic policies should take cognizance of the aetiological role played by this organism in pelvic inflammatory disease.

Matched MeSH terms: Pelvic Inflammatory Disease/etiology*
Nipah-virus encephalitis--investigation of a new infection

Farrar JJ

Lancet, 1999 Oct 9;354(9186):1222-3.
PMID: 10520625
Matched MeSH terms: Disease Outbreaks*
Australia's vital assistance to Asian nations fighting serious infectious diseases

Murray G

Aust. Vet. J., 1999 May;77(5):339.
PMID: 10376108
Matched MeSH terms: Communicable Disease Control/organization & administration*
Molecular characterization of Vibrio cholerae O1 outbreak strains in Miri, Sarawak (Malaysia)

Radu S, Vincent M, Apun K, Abdul-Rahim R, Benjamin PG, Yuherman, et al.

Acta Trop, 2002 Aug;83(2):169-76.
PMID: 12088858

Bacterial resistance to various antimicrobial agents is common in area with high usage of antibiotics. In this study, the data on antimicrobial susceptibility patterns of Vibrio cholerae O1 from patients during an outbreak period was found to be high but variable rates of multidrug resistance. Thirty-two of 33 V. cholerae isolates harboured the tcp, ctx, zot and ace genes, suggesting their possible roles in the outbreak cases. We analyzed the molecular diversity of a total of 33 strains of V. cholerae O1 isolated from 33 patients between November 1997 and April 1998 using random amplified polymorphic DNA (RAPD) analysis. The 30 typable isolates could be separated into four major clusters containing 5, 17, 2 and 6 isolates, respectively. However, no particular RAPD pattern was predictive of a particular pattern of antibiotic susceptibility. The findings of this study showed that multiple clones seemed to be responsible for cases in the outbreaks in the study area.

Matched MeSH terms: Disease Outbreaks*
Fulltext "Non-infectious" syndromes associated with infectious agents

Lim VKE

Med J Malaysia, 2000 Sep;55(3):389-97; quiz 398.
PMID: 11200726

Over the past two decades there has been numerous new associations between chronic diseases traditionally considered non-infectious with infectious agents. This list of diseases include peptic ulcer, coronary heart disease, neuropsychiatric disorders, haematological disorders and malignancies. These associations have been made possible through improvements in diagnostic tests based on molecular biology techniques. The discovery of these associations is important as it opens up exciting opportunities for the prevention and treatment of many diseases hitherto considered incurable.

Matched MeSH terms: Coronary Disease/microbiology*
Racial differences in the prevalence of ulcerative colitis and Crohn's disease in Singapore

Lee YM, Fock K, See SJ, Ng TM, Khor C, Teo EK

J Gastroenterol Hepatol, 2000 Jun;15(6):622-5.
PMID: 10921415

BACKGROUND: The aim of this study was to determine the prevalence rates of inflammatory bowel disease in the different races in Singapore.
METHODS: The patients studied consisted of 58 people with an established diagnosis of ulcerative colitis (UC) and Crohn's disease (CD) as determined by a combination of clinical, radiological, endoscopic and histological criteria. The patients were residents of a well-defined geographical area in the northern part of Singapore and had been referred to the single regional hospital. Epidemiological data including sex, age, ethnicity, family history and disease type and extent were collected from case records and patient interviews.
RESULTS: There were 37 UC and 21 CD patients. Of the patients with UC, 67.5% were Chinese, 13.5% were Malay and 19% were Indian. The CD group consisted of 81% Chinese, 9.5% Malay and 9.5% Indian patients. The study population from which the patients were drawn was approximately 0.5 million in size.
CONCLUSIONS: The overall prevalence of UC was 6 per 100,000 and of CD was 3.6 per 100,000 in Singapore. There were disproportionately more Indians suffering from UC, with a prevalence of 16.2 per 100,000 in comparison with six per 100,000 for Chinese and seven per 100 000 for Malays. The relative risk of UC in Indians is 2.9-fold greater than for the Chinese (CI= 1.25-6.7) which was statistically significant. This trend was not seen for CD.

Matched MeSH terms: Crohn Disease/ethnology*

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