Quantifying how location and dose of botulinum toxin injections affect muscle paralysis

Despite the widespread use of botulinum toxin to treat muscle dystonias, no method exists to quantify muscle paralysis in either human or nonhuman models. In this study we examined how the location, dose, and volume of botulinum injection affects paralysis in the rat tibialis anterior muscle. Paralysis was quantified by electrically stimulating the nerve to the tibialis anterior and then staining sections of the muscle for glycogen. The areas of glycogen-containing fibers represented regions of botulinum action. The results showed that the most important injection technique is to inject botulinum directly into the motor endplate region of a muscle. Injections only 0.5 cm from the motor endplate resulted in a 50% decrease in paralysis. Increases in dose increased paralysis, however, some of that increase was simply due to the increased volume of injection. Thus, delivering toxin in small volumes near the MEP band of a muscle should produce the most effectiveparalysis. © 1993 John Wiley & Sons, Inc.     

Tracheal Transplantation: Superior and Inferior Thyroid Artery Perfusion Territory

Objective: To determine the perfusion territories of the superior and inferior thyroid arteries in humans. Tracheal transplantation is a potential option for management of long-segment tracheal stenosis. However, the maximum length of vascularized trachea that can be reliably transplanted has not been established. Study Design: The tracheal vascular territory of individual superior and inferior thyroid arteries was determined separately in 10 humans postmortem. Methods: India ink was infused unilaterally under controlled pressure into the superior (n = 5) and inferior (n = 5) thyroid arteries of cadaveric tracheas. Tracheas were sectioned longitudinally and the caudalmost extent of mucosal dye staining was determined via microscopic assessment. Results: The tracheal perfusion territory of the superior thyroid artery was two to five rings (1.7 ± 0.5 cm) and the inferior thyroid artery, nine to 13 rings (6.5 ± 1.1 cm). In both cases, the tracheal mucosa on the contralateral side was stained to the same caudal level. Conclusions: The inferior thyroid artery was shown to perfuse the trachea maximally to the 13th ring (8.1 cm). As such, the unilateral inferior thyroid artery would serve as a suitable vascular component for long-segment tracheal transplantation in humans.     

Effect of storage time on metabolite profile and alpha-glucosidase inhibitory activity of Cosmos caudatus leaves – GCMS based metabolomics approach

Cosmos caudatus, which is a commonly consumed vegetable in Malaysia, is locally known as “Ulam Raja”. It is a local Malaysian herb traditionally used as a food and medicinal herb to treat several maladies. Its bioactive or nutritional constituents consist of a wide range of metabolites, including glucosinolates, phenolics, amino acids, organic acids, and sugars. However, many of these metabolites are not stable and easily degraded or modified during storage. In order to investigate the metabolomics changes occurring during post-harvest storage, C. caudatus samples were subjected to seven different storage times (0 hours, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, and 12 hours) at room temperature. As the model experiment, the metabolites identified by gas chromatography-mass spectrometry (GC-MS) were correlated with α-glucosidase inhibitory activity analyzed with multivariate data analysis (MVDA) to find out the variation among samples and metabolites contributing to the activity. Orthogonal partial least squares (OPLS) analysis was applied to investigate the metabolomics changes. A profound chemical alteration, both in primary and secondary metabolites, was observed. The α-tocopherol, catechin, cyclohexen-1-carboxylic acid, benzoic acid, myo-inositol, stigmasterol, and lycopenecompoundswerefoundtobethediscriminatingmetabolitesatearlystorage;however, sugars such as sucrose, α-d-galactopyranose, and turanose were detected, which was attributed to the discriminating metabolites for late storage. The result shows that the MVDA method is a promising technique to identify biomarker compounds relative to storage at different times.     

Overview of non-invasive factors (low level laser and low intensity pulsed ultrasound) accelerating tooth movement during orthodontic treatment

The need for orthodontic treatment is increasing all the time. As the treatment is time consuming ranging from a year to several years, any method of reducing the period of treatment and increasing the quality of the tissue will be beneficial to patients. The use of non-invasive techniques such as low level laser therapy and low intensity pulsed ultasound in accelerating orthodontic tooth movement are promising. Thus, this overview study will help to generate more understanding about the background information and the possible applications of them in daily orthodontics, depending on previous literature searching for reviews and original research articles.     

Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function

Aberrant signaling by oncogenic mutant rat sarcoma (Ras) proteins occurs in ∼15% of all human tumors, yet direct inhibition of Ras by small molecules has remained elusive. Recently, several small-molecule ligands have been discovered that directly bind Ras and inhibit its function by interfering with exchange factor binding. However, it is unclear whether, or how, these ligands could lead to drugs that act against constitutively active oncogenic mutant Ras. Using a dynamics-based pocket identification scheme, ensemble docking, and innovative cell-based assays, here we show that andrographolide (AGP)—a bicyclic diterpenoid lactone isolated from Andrographis paniculata—and its benzylidene derivatives bind to transient pockets on Kirsten-Ras (K-Ras) and inhibit GDP–GTP exchange. As expected for inhibitors of exchange factor binding, AGP derivatives reduced GTP loading of wild-type K-Ras in response to acute EGF stimulation with a concomitant reduction in MAPK activation. Remarkably, however, prolonged treatment with AGP derivatives also reduced GTP loading of, and signal transmission by, oncogenic mutant K-RasG12V. In sum, the combined analysis of our computational and cell biology results show that AGP derivatives directly bind Ras, block GDP–GTP exchange, and inhibit both wild-type and oncogenic K-Ras signaling. Importantly, our findings not only show that nucleotide exchange factors are required for oncogenic Ras signaling but also demonstrate that inhibiting nucleotide exchange is a valid approach to abrogating the function of oncogenic mutant Ras.     

Parasitic infections among Orang Asli (aborigine) in the Cameron Highlands, Malaysia

In April 2004, an outbreak of acute diarrheal illness occurred among the Orang Asli (aborigine) in the Cameron Highlands, Pahang State, Peninsular Malaysia, where rotavirus was later implicated as the cause. In the course of the epidemic investigation, stool samples were collected and examined for infectious agents including parasites. Soil transmitted helminthes (STH), namely Ascaris lumbricoides (25.7%), Trichuris trichiura (31.1%) and hookworm (8.1%), and intestinal protozoa, which included Giardia lamblia (17.6%), Entamoeba histolytica/E. dispar (9.4%), Blastocystis hominis (8.1%) and Cryptosporidium parvum (2.7%), were detected. Forty-four (59.5%) were infected with at least one parasite, 24 (32.4%), 12 (16.2%) and 8 (10.8%) had single, double and triple parasitic infections, respectively. STH were prevalent with infections occurring as early as in infancy. Giardia lamblia, though the most commonly found parasite in samples from symptomatic subjects, was within the normally reported rate of giardiasis among the various communities in Malaysia, and was an unlikely cause of the outbreak. However, heavy pre-existing parasitic infections could have contributed to the severity of the rotavirus diarrheal outbreak.     

Comparison of peri-prosthetic bone density in cemented and uncemented total knee arthroplasty

The aim of our study was to assess the effect of knee replacement with or without bone cement on periprosthetic bone density. Periprosthetic bone density in two comparable groups (30 each) of cemented and uncemented knee replacements was measured with DEXA scanner. Bone loss was more in the area posterior to the anterior femoral flange in the cemented subgroup, nearing statistical significance (p = 0.059). In both groups, the reported bone density at a median of four years postoperatively was reduced at several periprosthetic sites. However, the method of fixation could not be clearly demonstrated to influence the bone loss differentially. This brings into question the use of the more expensive cementless implants. Reduction in bone density in both groups at several periprosthetic sites remains a concern. Whether or not this can be addressed with medical intervention like post arthroplasty bisphosphonate treatment needs further consideration.     

Health values of patients with systemic sclerosis

OBJECTIVE: To assess health values in subjects with systemic sclerosis (SSc) and determine variability explained by demographics, clinical factors, health status, and disease severity. METHODS: We interviewed 107 individuals with SSc who attended national and local Scleroderma Foundation meetings in 2005. Health status was measured using the Short Form 36 (SF-36) Physical Component Summary (PCS; range 0-100) and Mental Component Summary (MCS; range 0-100), the Center for Epidemiologic Studies Depression Scale (CES-D; range 0-60), and the Health Assessment Questionnaire (HAQ) disability index (DI; range 0-3). Disease severity was assessed using a visual analog scale (VAS; range 0-150). Health value measures included the 0-100 health rating scale (RS), standard gamble (SG; range 0.0-1.0), and time trade-off (TTO; range 0.0-1.0). We performed univariate analyses to compare scores between participants with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), and multivariable analyses for 3 outcome measures: RS, SG, and TTO, controlling for demographics, type of SSc, health status, and disease severity. RESULTS: Of the 107 participants, 48 had dcSSc and 59 had lcSSc. Ninety-seven were women and 83 were white. The median scores for the PCS, MCS, and HAQ DI were 36.9, 45.5, and 0.9, respectively. Fifty-five subjects had significant depressive symptoms (CES-D score >or=16). The median RS, SG, and TTO scores were 62, 0.83 (indicating a willingness to accept up to a 17% risk of immediate death in exchange for perfect health), and 0.88 (indicating a willingness to give up a median of 12% of life expectancy in exchange for perfect health), respectively. Subjects with dcSSc had lower RS scores but higher SG scores (corresponding to a willingness to accept only a smaller risk of death) than subjects with lcSSc. TTO scores were similar in the 2 groups. Health values were variably related to factors such as demographics, VAS score, disease classification, and SF-36 PCS and MCS scores (R(2) = 0.22, 0.23, and 0.66 for the SG, TTO, and RS models, respectively). CONCLUSION: Individuals with dcSSc have lower health ratings but higher SG health values than individuals with lcSSc. These findings have implications for decision analysis and cost-effectiveness analysis.     

Complications of head and neck surgery in the elderly.

Many recent studies have documented that complications of head and neck surgery are no more common in the elderly than in younger patients. But few studies have addressed complication rates in a population undergoing reconstruction with microvascular free tissue transfer (MFTT). We compared outcomes of patients older and younger than 70 who underwent MFTT and found no significant difference in the incidence of surgical complications. However, older patients did experience more medical morbidity and more surgical mortality. Nonetheless, we conclude that MFTT should not be withheld from patients 70 years and older solely on the basis of their advanced age.     

Bioassay-Guided Isolation of a Potent Platelet-Activating Factor Antagonist Alkenylresorcinol from Ardisia elliptica

In the course of our search for novel platelet-activating factor (PAF) antagonists from medicinal plants, the methanol extract of the leaves of Ardisia elliptica Thunb. was investigated for its inhibitory effects on PAF receptor binding to rabbit platelets using ³H-PAF as a ligand. The methanol extract showed inhibitory activity of 53.9% and its ethyl acetate, n-butanol, and methanol fractions exhibited 48.6%, 39.0%, and 22.0% inhibition, respectively. Bioassay-guided fractionation of the ethyl acetate fraction led to the isolation of a new alkenylresorcinol, 5-(Z-heptadec-4′-enyl)resorcinol, together with 5-pentadecylresorcinol. The alkenylresorcinol showed a strong inhibition with an IC₅₀ value of 7.1 µM. The structures of the compounds were elucidated by spectroscopic techniques.