Anaesthetic considerations in a patient with lepromatous leprosy

PURPOSE: To consider the anaesthetic problems in a patient with lepromatous leprosy undergoing general anaesthesia. CLINICAL FEATURES: A 52 yr old man with lepromatous leprosy for five years was booked for elective radical nephrectomy. He received 100 mg dapsone per day po. The patient was asymptomatic for cardiovascular disease but his electrocardiogram showed complete left bundle branch block, inferior wall ischaemia with echocardiogram findings of 58% ejection fraction and left ventricular diastolic dysfunction. Other preoperative investigations (haemogram, serum urea and creatinine, liver function tests and chest X-ray) were normal. After premedication with diazepam, meperidine and promethazine, the patient received glycopyrrolate and anaesthesia was induced with thiopentone. Atracurium was given to facilitate tracheal intubation. Anaesthesia was maintained with intermittent positive pressure ventilation using N2O in oxygen with halothane. Anaesthesia and surgery were uneventful except that the patient had a fixed heart rate that remained unchanged in response to administration of anticholinergic, laryngoscopy, intubation and extubation. CONCLUSION: Patients with lepromatous leprosy may have cardiovascular dysautonomia even when they are asymptomatic for cardiovascular disease.     

4-Hydroxyisoleucine stimulates glucose uptake by increasing surface GLUT4 level in skeletal muscle cells via phosphatidylinositol-3-kinase-dependent pathway

Purpose

To determine the effect of 4-Hydroxyisoleucine (4-HIL), an unusual amino acid isolated from the seeds of Trigonella foenum-graecum, on glucose uptake and the translocation of glucose transporter 4 (GLUT4) to plasma membrane in skeletal muscle cells and to investigate the underlying mechanisms of action.

Methods

Rat skeletal muscle cells (L6-GLUT4myc) were treated with 4-HIL, and the effect on glucose uptake was determined by measuring the incorporation of radio-labeled 2-deoxy-[³H]-d-glucose (2-DG) into the cell. Translocation of GLUT4myc to plasma membrane was measured by an antibody-coupled colorimetric assay.

Results

The prolonged exposure (16?h) of L6-GLUT4myc myotubes to 4-HIL caused a substantial increase in the 2-DG uptake and GLUT4 translocation to the cell surface, without changing the total amount of GLUT4 and GLUT1. Cycloheximide treatment reversed the effect of 4-HIL on GLUT4 translocation to the basal level suggesting the requirement of new protein synthesis. The 4-HIL-induced increase in GLUT4 translocation was completely abolished by wortmannin, and 4-HIL significantly increased the basal phosphorylation of AKT (Ser-473), but did not change the mRNA expression of AKT, IRS-1, GLUT4, and GSK3β.

Conclusion

Results suggest that 4-HIL stimulates glucose uptake in L6-GLUT4myc myotubes by enhancing translocation of GLUT4 to the cell surface in a PI-3-kinase/AKT-dependent mechanism.     

Antibacterial substances from Albizia myriophylla wood against cariogenic Streptococcus mutans

Albizia myriophylla has been used for long by Thai traditional healers as an important ingredient herb in Thai herbal formulas for caries. In this study, three flavonoids lupinifolin (6), 8-methoxy-7,3′,4′-trihydroxyflavone (7), and 7,8,3′,4′-tetrahydroxyflavone (8), a triterpenoid lupeol (3) as well as four sterols β-sitosterone (1), stigmasta-5,22-dien-3-one (2), β-sitosterol (4), and stigmasterol (5) were isolated from A. myriophylla wood. The antibacterial activity of these compounds against Streptococcus mutans ATCC 25175 was performed using broth microdilution method. All compounds exhibited antibacterial activity against S. mutans with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) ranging from 1–256 and 2–256 μg/ml, respectively. Among the isolated compounds, lupinifolin (6) was found to be the most potent with MIC and MBC of 1 and 2 μg/ml, respectively. Lupinifolin (6) also showed a strong activity against ten clinical isolates of S. mutans with MIC and MBC ranging from 0.25–2 and 0.5–8 μg/ml, respectively. These results reported the bioactive ingredients of A. myriophylla which support its ethnomedical claims as well. Lupinifolin (6) may have a potential to be a natural anticariogenic agent.     

Genome-wide association studies of tuberculosis in Asians identify distinct at-risk locus for young tuberculosis

Tuberculosis (TB) is one of the most devastating chronic infectious diseases, but the role of host genetics in disease development after infection in this disease remains unidentified. Genome-wide association studies (GWASs) in Thais and Japanese were carried out and separately analyzed, attempted replication, then, combined by meta-analysis were not yielding any convincing association evidences; these results suggested that moderate to high effect-size genetic risks are not existed for TB per se. Because of failure in replication attempt of the top 50 single-nucleotide polymorphisms (SNPs) identified form meta-analysis data, we empirically split TB cases into young TB case/control data sets (GWAS-T(young)=137/295 and GWAS-J(young)=60/249) and old TB case/control data sets (GWAS-T(old)=300/295 and GWAS-J(old)=123/685), re-analyzed GWAS based on age-stratified data and replicated the significant findings in two independent replication samples (young TB; Rep-T(young)=155/249, Rep-J(young)=41/462 and old TB; Rep-T(old)=212/187, Rep-J(old)=71/619). GWAS and replication studies conducted in young TB identified at-risk locus in 20q12. Although the locus is located in inter-genic region, the nearest genes (HSPEP1-MAFB) from this locus are promising candidates for TB susceptibility. This locus was also associated with anti-TNF responsiveness, drug with increased susceptibility for TB. Moreover, eight SNPs in an old TB meta-analysis and six SNPs in young TB meta-analysis provided replication evidences but did not survive genome-wide significance.These findings suggest that host genetic risks for TB are affected by age at onset of TB, and this approach may accelerate the identification of the major host factors that affect TB in human populations.     

Simple, sensitive and reliable in vivo assays to evaluate the estrogenic activity of endocrine disruptors

Purpose

We compared three in vivo assays, determining changes of body weight, and uterotropic and vaginal cytology assays, for the evaluation of estrogenic activity of an estrogen disrupting compound, Pueraria mirifica (PM), in comparison with 17β-estradiol (E).

Methods

Female rats were ovariectomized and gavaged with distilled water, 0.01, 0.1, 1, 10 and 20 mg/kg BW/day of E and 100 and 1,000 mg/kg BW/day of PM for 14 days. Body weights were measured weekly, and vaginal epithelium cells were monitored daily. The uterus was dissected at the end of the treatment period, weighed and examined for histomorphometry.

Results

There were a decrease in body weight and an increase in uterine weight, uterine, endometrium and myometrium areas, uterine gland numbers, and percent of cornified cell which were dependent on doses of E and PM treatments.

Conclusions

Of the three assays proposed, although all are reliable and had critical read-out, measurements of body and uterine weights is likely convenient and simple, but the uterotropic assay needs to kill the animals. Vaginal cytology assay appears most promising for sensitivity and shortening the duration of the assay. Compared to those of E, the estrogenic activity of PM at concentrations of 100 and 1,000 mg/kg BW was in the range of 14 to >20 mg/kg BW.     

Management of Upper Extremity Vascular Injury: Outcome Related to the Mangled Extremity Severity Score

Background  The Mangled Extremity Severity Score (MESS) is an objective criterion for amputation prediction after lower extremity injury as well as for amputation prediction after upper extremity injury. A MESS of ≥7 has been utilized as a cutoff point for amputation prediction. In this study, we examined the result of upper extremity vascular injurty (UEVI) management in terms of the amputation rate as related to the MESS. Methods  During January 2002 to July 2007, we reviewed patients with UEVIs at our institution. Data collections included demographic data, mechanism of injuries, injury severity score (ISS), ischemic time, MESS, pathology of UEVI, operative management, and amputation rate. Decisions to amputate the injured limbs at our institution were made individually by clinically assessing limb viability (i.e., color and capillary refill of skin; color, consistency, and contractility of muscles) regardless of the MESS. The outcome was analyzed in terms of the amputation rate related to the MESS. Results  There were 52 patients with UEVIs in this study: 25 (48%) suffered blunt injuries and 27 (52%) suffered penetrating injuries. The age ranged from 15 to 59 years (mean 28.7 years). The mean ischemia time was 10.07 h. The mean ISS was 17.52. There were 12 patients (23%) with subclavian artery injuries, 3 patients (5.76%) with axillary artery injuries, 18 patients (34.61%) with brachial artery injuries, and 19 patients (36.54%) with radial artery and/or ulnar artery injuries. Primary repairs were performed in 45 patients (86.54%), with ligations in 3 patients (5.77%). An endovascular stent-graft was used in one patient (1.92%). Primary amputations were performed in three patients (5.77%). Secondary amputations (amputation after primary operation) were done in 4 of 49 patients (secondary amputation rate 8.16%). All amputation patients suffered blunt injuries and had a MESS of ≥7 (range 7–11). The overall amputation rate in this study was 13.46% (7/52 patients). Multivariate analysis revealed that the only factor significantly associated with amputation was the MESS. There were no amputations in 33 patients who had a MESS of <7. We could avoid amputation in 12 of 19 patients who had a MESS ≥7. There were no mortalities among 52 UEVI patients. Conclusions  MESS, an outcome score used to grade the severity of extremity injuries, correlates well with the risk of amputation. Nevertheless, a MESS of ≥7 does not always mandate amputation. On the other hand, the MESS is a better predictor for patients who do not require amputation when the score is <7. The decisions to amputate in patients should be made individually based on clinical signs and an intraoperative finding of irreversible limb ischemia.