Electrical stimulation-evoked contractions blunt orthostatic hypotension in sub-acute spinal cord-injured individuals: two clinical case studies.

STUDY DESIGN: Prospective study of two cases. OBJECTIVES: To describe the effects of electrical stimulation (ES) therapy in the 4-week management of two sub-acute spinal cord-injured (SCI) individuals (C7 American Spinal Injury Association Impairment Scale (AIS) B and T9 AIS (B)). SETTING: University Malaya Medical Centre, Kuala Lumpur, Malaysia. METHODS: A diagnostic tilt-table test was conducted to confirm the presence of orthostatic hypotension (OH) based on the current clinical definitions. Following initial assessment, subjects underwent 4 weeks of ES therapy 4 times weekly for 1 h per day. Post-tests tilt table challenge, both with and without ES on their rectus abdominis, quadriceps, hamstrings and gastrocnemius muscles, was conducted at the end of the study (week 5). Subjects' blood pressures (BP) and heart rates (HR) were recorded every minute during pre-test and post-tests. Orthostatic symptoms, as well as the maximum tolerance time that the subjects could withstand head up tilt at 60°, were recorded. RESULTS: Subject A improved his orthostatic symptoms, but did not recover from clinically defined OH based on the 20-min duration requirement. With concurrent ES therapy, 60° head up tilt BP was 89/62 mm Hg compared with baseline BP of 115/71 mm Hg. Subject B fully recovered from OH demonstrated by BP of 105/71 mm Hg during the 60° head up tilt compared with baseline BP of 124/77 mm Hg. Both patients demonstrated longer tolerance time during head up tilt with concomitant ES (subject A: pre-test 4 min, post-test without ES 6 min, post-test with ES 12 min; subject B: pre-test 4 min, post-test without ES 28 min, post-test with ES 60 min). CONCLUSIONS: Weekly ES therapy had positive effect on OH management in sub-acute SCI individuals.

Curcumin induces apoptosis of 3T3-L1 adipocytes and affects molecular signals of adiponectin, AMPK and PKA Ebtesam / La curcumina inhibe la viabilidad celular e induce la apoptosis mediante la modulación de la adiponectina, la AMPK y PKA en adipocitos 3T3-L1

Apoptosis is an important cellular physiological function to continually balance the cell proliferation with cell death to maintain the healthy internal milieu. This study assessed the ability of Curcumin to inhibit 3T3-L1 adipocytes viability and its effects on apoptosis to identify a potential molecular approach for preventing adipocytes growth. To optimize the growth inhibitory concentration 3T3-L1 adipocytes treated with different concentrations of Curcumin (5, 10, 20, 40, 60, and 80 μM) for 24 hours, and were analyzed by MTT and found 40 μM as an optimal dose. Cell cycle was analysed by FACS using the optimal dose for different periods (4-24h). Western blot was carried out using antibodies to detect protein expression and Phosphorylation of Adiponectin, AMPK, CREB, PKA catalytic subunit, and Akt. PKA relative activity and ROS generation was also assessed by DCFHDA fluorescence. The findings of the study revealed that Curcumin has successfully arrested 3T3L1 adipocytes cycle and exerted apoptotic action on the cells in a concentration- time dependent manner; increased Adiponectin expression; activated phosphorylated AMPK (p-AMPK) and inhibited PKA activation. Curcumin prevented the production of ROS generation. Results indicate that Curcumin exerts a very potent apoptotic action on 3T3L1 adipocytes and modulates adiponectin expression and AMPK and PKA signalling. These findings lead us to further investigate and support the potential use of Curcumin therapy in obesity resistance

La apoptosis es una función fisiológica celular importante para equilibrar de manera continua la proliferación y la muerte celulares con el objeto de mantener el entorno interno sano. Este estudio se determina la capacidad de la curcumina de inhibir la viabilidad de los adipocitos 3T3-L1 y sus efectos sobre la apoptosis para identificar un posible acercamiento molecular para prevenir el crecimiento de los adipocitos. Para optimizar la concentración inhibitoria del crecimiento, los adipocitos 3T3-L1 han sido tratados con diversas concentraciones de curcumina (5, el μM 10, 20, 40, 60, y 80) durante 24 horas y analizados por MTT, encontrando el μM 40 como dosis óptima. El ciclo de la célula ha sido analizado por FACS usando la dosis óptima en diversos períodos (4-24h). El Western blot se realizó usando los anticuerpos para detectar la proteína y la fosforilación de la adiponectina, de la subunidad catalítica de AMPK, de CREB, de PKA, y de Akt. La actividad relativa de PKA y la generación del ROS también fueron determinadas por fluorescencia de DCFHDA. Los resultados del estudio revelaron que la curcumina ha detenido con éxito el ciclo de los adipocitos 3T3L1 y que la acción apoptótica ejercida en las células en una concentración mide el tiempo de manera dependiente; expresión creciente de adiponectina; AMPK fosforilado activado (p-AMPK) y activación inhibida de PKA. La curcumina previno la producción de la generación del ROS. Los resultados indican que la curcumina ejerce una acción apoptótica muy potente en los adipocitos 3T3L1 y modula la expresión de la adiponectina indicando AMPK y PKA. Estos resultados nos conducen a ir más lejos en la investigación y el uso potencial de la terapia de la curcumina para combatir la obesidad

Clinical-Epidemiological Pattern of Primary Immunodeficiencies in Malaysia 1987-2006: A 20 year experience in Four Malaysian Hospitals.

AIM OF STUDY: To determine the clinical and epidemiological characteristics of patients seen with primary immunodeficiencies referred at four Malaysian Hospitals between 1987 to 2007. METHODS: Patient data were retrospectively obtained from patient records and supplemented by information from a standardized questionnaires taken at the time of diagnosis from 4 participating hospitals. The completed data were transferred to document records kept by the first author. The diagnoses made were based on criteria set by WHO Scientific Committee 1986. RESULTS: Fifty one (51) patients with completed records satisfied the criteria of primary immunodeficiencies based on WHO Scientific Committee 1986. Predominant Antibody deficiency (40.4%) is the commonest of the class of primary immunodeficiency (based on modified IUIS classification) followed by phagocytic defect (17.3%), combined immunodeficiencies (15.4%) and other cellular immunodeficiencies (11.5%). The commonest clinical presentation is pneumonia (54%) . A positive Family history with a close family relative afflicted was a strong pointer to diagnosis for PID (52.6%) Primary immnodeficiencies are seen in all the major ethnic groups of Malaysia, predominantly among Malays. As observed in other patient registries, diagnostic delay remains the major cause of morbidity and mortality. CONCLUSION: Primary immunodeficiencies is relative rare but is an emerging disease in Malaysia. Creating awareness of the disease, may reveal more cases within the community. It is sufficient to be a health issue in Malaysia as in other developing countries in the future.

Population pharmacokinetic modelling of repaglinide in healthy volunteers by using Non-Parametric Adaptive Grid Algorithm.

OBJECTIVE: To estimate population pharmacokinetic parameters of repaglinide in 121 healthy Malaysian volunteers. METHODS: Each subject received 4 mg of oral repaglinide. Six blood samples were taken per individual (0, 30, 60, 120, 180 and 240 min) for repaglinide's serum concentration determination by using high-performance liquid chromatography. The parametric Iterative Two-Stage Bayesian Population Model (it2b) program followed by the Non-Parametric Adaptive Grid (npag) program was used to determine a population pharmacokinetic modelling of repaglinide. RESULTS: Using the npag program, the mean elimination rate constant (k(el)) of repaglinide was 0.58 +/- 0.27 h and the volume of distribution (V(d)) was 23.09 +/- 9.19 L/h. CONCLUSION: In this first report, specifically on the population pharmacokinetic modelling of repaglinide, the data generated should help us to better understand appropriate dosage-regimens for the drug.

The association between pre-morbid conditions and respiratory tract manifestations amongst Malaysian Hajj pilgrims

In a very closed and overcrowding environment, influenza transmission during Hajj season is almost inevitable. The aim of this study was to determine the association between pre-morbid conditions and influenza-like illness (ILI) amongst Hajj pilgrims. A cross-sectional study was conducted amongst Malaysian Hajj pilgrims in year 2007. Survey forms were distributed at Madinatul-Hujjaj, Jeddah and Tabung Haji Clinic, Medina, Saudi Arabia where pilgrims stay on transit before returning to Malaysia. Allergic rhinitis was significantly associated with sore throat (p=0.047), longer duration of cough (p= 0.017) and runny nose (p=0.016). Pilgrims who suffered from chronic obstructive pulmonary diseases (COPD) had significant association with longer duration of cough (p=0.041) and those with diabetes mellitus had significant association with longer duration of sore throat (p=0.048). Underlying asthma was significantly associated with severe influenza like illness requiring admission to hospital for further treatment of respiratory symptoms (p=0.016). Based on these findings, we suggest those with underlying asthma should be discouraged from participating in the hajj and they should seek early treatment if they develop respiratory symptoms.

Genetic polymorphisms of CYP3A4: CYP3A4*18 allele is found in five healthy Malaysian subjects.

BACKGROUND: Cytochrome P450 3A4 (CYP3A4) is the major cytochrome involved in metabolizing of >60% of all drugs used in humans. A number of allelic variations in CYP3A4 gene are known to affect catalytic activity including CYP3A4*4, CYP3A4*5 and CYP3A4*18. We investigated the frequencies of CYP3A4*4, CYP3A4*5 and CYP3A4*18 alleles in a Malaysian population. This will impact treatment of patients receiving drugs metabolized by these alleles. METHODS: The study was conducted in 121 healthy Malaysian volunteers. DNA was extracted from leucocytes and the 3 alleles were determined by PCR-RFLP. The PCR product was later digested with restriction enzymes BstMA I, BshV I and Hpa II. RESULTS: No mutations were detected for CYP3A4*4 and CYP3A4*5 alleles. The frequency of the CYP3A4*18 allele in the Malaysian population is 2.1%. All 5 subjects with CYP3A4*18 mutations were found to be heterozygous. CONCLUSION: The present study describes polymorphisms of CYP3A4 among Malaysian subjects. Clinical relevance of these genetic variants in these healthy volunteers is under investigation.

Favourable response to splenectomy in familial myelodysplastic syndrome.

Familial myelodysplastic syndrome occurring at a young age is a very rare childhood haematological malignancy. Two siblings, aged three and 18 years, from a consanguineous marriage, presented with pancytopenia and was subsequently diagnosed to have myelodysplastic syndrome. Both remained clinically stable throughout the illness. Splenectomy appeared to have fully corrected the cytopenia in one of them.

Malaysian Indians are genetically similar to Caucasians: CYP2C9 polymorphism.

BACKGROUND: CYP2C9 is one of the major drug metabolizing enzymes for many drugs including warfarin, NSAIDs and losartan. It is polymorphic in many populations. Data on the distribution of CYP2C9 and the implication of CYP2C9 polymorphism in the Malaysian population is lacking. Our objectives were therefore to investigate the prevalence of CYP2C9 variants among unrelated healthy volunteers of Malays, Chinese and Indians in Malaysia. METHOD: Deoxyribonucleic acid was extracted using standard lysis methods. Allele specific polymerase chain reaction was performed for determination of CYP2C9*1, *2, *3, *4 and *5 variants according to Z. Zainuddin, L.K. Teh, A.W.M. Suhaimi, M.Z. Salleh, R. Ismail (2003, Clinica Chimica Acta, 336, 97). RESULT: The Chinese had the highest frequency of CYP2C9*1 (321/330, 97.27%), followed by the Malays and the Indians (402 of 420, 95.71% and 291 of 330, 88.18%, respectively). CYP2C9*2 was not found in the Chinese. CYP2C9*3 were detected in all the three races with the Indians having the highest frequency of CYP2C9*3 (9.7%). The Indians had a frequency of CYP2C9*2 and *3 similar to Tamilians and Caucasians. Two of the Indians had *2/*3 and one had *3/*3 genotypes and are likely to be slow metabolizers. No subject with CYP2C9*4 and *5 were detected in our populations. CONCLUSION: CYP2C9*2 and *3 were identified in our population. Indians are similar to Caucasians in terms of CYP2C9 genotypes and thus may respond to CYP2C9 substrates differently when compared with the Malays and Chinese in Malaysia.

A simple method for the detection of CYP2C9 polymorphisms: nested allele-specific multiplex polymerase chain reaction.

BACKGROUND: Cytochrome P4502C9 (CYP2C9), a principle drug-metabolizing enzyme is polymorphic in humans and is responsible for important pharmacokinetic and pharmacodynamic variations of CYP2C9 substrates. We developed an allele-specific multiplex polymerase chain reaction (PCR) method for the detection of common CYP2C9 alleles. METHOD: Genomic DNA was extracted from blood obtained from 40 unrelated healthy Malaysian Indian volunteers. The DNA was subjected to a first PCR that was used to amplify both exons 3 and 7 simultaneously in one reaction tube and a second PCR that was used to detect the polymorphic sites of CYP2C9 alleles using allele-specific primers. Sequencing was performed to validate the test results. RESULTS: We were successful in amplifying the fragments of interest from the DNA samples. The method was also reproducible and specific. The amplified sequences showed 100% homology to CYP2C9 sequence. CONCLUSION: This is the first nested allele-specific multiplex PCR method reported to allow for the simultaneously detection of five CYP2C9 alleles.

Prevalence of antibodies to Pseudomonas pseudomallei exotoxin and whole cell antigens in military personnel in Sabah and Sarawak, Malaysia.

Sera from 420 military personnel serving in Sabah and Sarawk, Malaysia, were tested for antibodies to Pseudomonas pseudomallei exotoxin and whole cell antigens by enzyme-linked immunosorbent assay procedure (ELISA). Data showed that 54.4% of serum samples were positive for antibodies to P. pseudomallei exotoxin and 65.7% were positive for antibodies to the whole cell antigens. Samples gave much lower titers for anti-exotoxin antibodies compared to titers against crude whole cell antigens. The incidence of antibody to exotoxin was highest in the age groups ranging from 26 to 32 years, where the positive rates were higher than 40% and 30% for military personnel serving in Sarawak and Sabah, respectively.

Paramedic insertion of intrauterine device in a Malaysian family planning clinic.

PIP: A study was done by the Malaysian family planning clinic to check the feasibility in using paramedical personnel to insert IUDs. There were 250 insertions by trained senior nurses and 369 insertions by doctors. In the follow-up, no differences were found in terminations due to IUD complications, and also none in terminations for pregnancy, bleeding, pain, expulsion and pelvic infections. Studies in Turkey, Philippines, Korea, Iran, and Thailand showed similar results in that paramedical personnel are just as effective as doctors in the insertion of IUDs. The follow-up was done in this study by nurses at 6 weeks, 3 months, and 6 months and from then, on a yearly basis. There was a large unexplained loss of follow-up in the nurses group, 12.7% and only 6% in the doctors. There was a 8.9% rate for removal for a planned pregnancy, and both groups had a high continuation rate: 63.3% for nurses and 70.5% for doctors. The conclusion of the study indicates that trained paramedical people can perform insertion of IUD's as effectively as doctors when there are no medical or gynecological problems in the patients. It is also noted that in some areas women prefer to have nurses do the insertion because of their conservative nature.^ieng