The role of the Back Rx exercise program in diskogenic low back pain: a prospective randomized trial

OBJECTIVE: To determine the efficacy of the Back Rx program in patients with diskogenic low back pain (LBP). DESIGN: Prospective, randomized study. SETTING: Outpatient setting of a major university teaching hospital. PARTICIPANTS: Subjects with LBP greater than leg pain for at least 3 months duration and magnetic resonance imaging evidence of disk pathology. Fifty of 87 eligible patients consented and were randomized into age- and sex-matched groups. INTERVENTIONS: Group I participated in the Back Rx program for 15 minutes a day, 3 times a week. All patients, from both groups, received celecoxib (200 mg) and hydrocodone (5 mg) with acetaminophen (500 mg) as needed, and wore a lumbar cryobrace for 15 minutes before bedtime. MAIN OUTCOME MEASURES: Roland-Morris Disability Questionnaire score, numeric pain rating score, patient satisfaction score, measured forward flexion, use of celecoxib, hydrocodone, and acetaminophen, time off work, and rate of symptom recurrence. RESULTS: At minimal 12-month follow-up, 70% of group I reported over 50% pain reduction with good or better patient satisfaction, compared with 33% in group II (P=.001). Average daily hydrocodone and acetaminophen use and time off work were less for group I (all, P<.05). Recurrence of symptoms at the end of the year was less for group I (P=.001). CONCLUSIONS: Back Rx exercises, combined with use of a lumbar cryobrace and oral medications, yielded superior therapeutic results than with use of medications and cryobrace alone. Also significant was the reduced rate of recurrence in these patients.     

Efficacy and tolerability of prochlorperazine buccal tablets in treatment of acute migraine

OBJECTIVES: To study the efficacy and tolerability of prochlorperazine (PCZ) management of acute migraine. DESIGN AND METHODS: A double blind comparative study was conducted to assess the efficacy of buccal PCZ 3 mg compared with oral ergotamine tartarate 1 mg plus caffeine 100 mg (ERG) or placebo (buccal or oral) for treatment of acute migraine. In all, 114 episodes of acute migraine were evaluated. Patients graded symptoms on a four-point scale before and up to 4 hours after treatment. The primary efficacy parameters included headache resolution within 2 hours (grade 3 or 2 to grade 0) and alleviation of other accompanying symptoms of migraine. The supplementary endpoints included improvement in quality of life (QOL). RESULTS: The percentage of patients reporting resolution of headache (to grade 0) was 51.4% for buccal PCZ and 21.7% for buccal placebo, 23.1% for oral ERG and 28.6% for oral placebo, headache tended to recur in both the placebo and ERG groups after initial improvement. Buccal PCZ was well tolerated; no signs of local irritation were evident, and patients found the formulation easy to use. Mild but transient sedation and drowsiness were observed in 41%. CONCLUSIONS: In the present study, PCZ 3 mg via the buccal route produced faster improvement and greater efficacy than placebo (oral as well as buccal) or oral ERG. The global QOL score 2 hours after treatment scores was higher in the PCZ group. Buccal PCZ may represent a particularly effective alternative for acute migraine treatment.     

Analysis of blood glucose measurements using capillary and arterial blood samples in intensive care patients

Objective To analyse agreement between two methods for blood glucose measurement in intensive care patients: capillary blood using a reagent strip and glucometer with arterial blood using a blood gas analyser.Design and setting Prospective, single-centre, observational study in a 12-bed tertiary referral intensive care unit.Measurements Blood glucose levels were measured in consecutive patients using simultaneous measurements of capillary blood samples using glucometry and from a multi-electrode arterial blood gas analyser. An a priori subgroup of patients with tissue hypoperfusion was identified (defined as systolic blood pressure <90 mmHg or vasopressor dependency). A total of 493 paired measurements were obtained; 75 of these were from patients with systemic hypoperfusion.Results Overall, the mean difference (bias) was 0.12 mmol/l (2.15 mg/dl) and precision 0.77 mmol/l (13.8 mg/dl); 95% limits of agreement were –0.14 and 1.66 mmol/l (–2.5 and 29.8 mg/dl). In patients with systemic hypoperfusion the bias was 0.24 mmol/l (4.0 mg/dl) and precision 0.9 mmol/l (16.2 mg/dl); 95% limits of agreement –2.05 and 1.58 mmol/l (36.8 and 28.4 mg/dl).Conclusions In a general population of intensive care patients, there is statistical agreement between blood glucose measured from capillary blood glucometry and arterial blood gas analysis. However, in patients with systemic hypoperfusion, the accuracy of agreement between these two measurement techniques may be such that that biochemical hypoglycaemia (<2.5 mmol/l, 44.9 mg/dl) may go undetected if used interchangeably.     

Chromenone and quinolinone derivatives as potent antioxidant agents

The antioxidant activity (AOA) of three different classes of phenolic compounds viz chromen-2-ones, chromen-4-ones, and quinolin-2-ones was systematically studied using DPPH, ABTS, FRAP, and in vitro lipid peroxidation inhibition assays. The effect of incorporation of hydrophobic group on AOA was also studied. In DPPH, ABTS, and FRAP assays, the highest AOA was registered for the dihydroxy chromenones among all the phenolic derivatives. Presence of alkyl group led to reduction in AOA in the above three assays. However, in lipid peroxidation inhibition assay for selected compounds, incorporation of alkyl group led to enhancement in AOA. The AOA of few compounds was observed to be more than three times higher in comparison to standard “Trolox” in lipid peroxidation inhibitory assay.     

Synthesis,anti-inflammatory and antioxidant activity of ring-A-monosubstituted chalcone derivatives

A library of ring-A-monosubstituted chalcone derivatives (4a–4i, 5a and 5b) was designed and synthesised. The structures as well as the identities of these compounds were established on the basis of spectral (¹H NMR, ¹³C NMR, FT-IR and Mass) and elemental (C, H, N) analyses. All the derivatives were evaluated for their anti-inflammatory and antioxidant activities in vitro using the inhibition of protein denaturation and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays, respectively. The results indicated a promising anti-inflammatory activity for most of the synthesised compounds with many derivatives showing activities similar to or greater than that of the standard. The sulphonamide-substituted chalcones 4h, 4i, 5a and 5b were found to be the most active derivatives across the concentration range tested. However, all the derivatives exhibited rather mild antioxidant activity compared to the ascorbic acid standard. Interestingly, it was observed that the unsubstituted parent chalcone was one of the optimal compounds with only the trifluoromethyl analogue 4a showing better activity as an antioxidant. The two regioisomeric aminochalcones and 4′-cyanochalcone 4b also seemed to possess decent antioxidant potential.     

Microneedle-Assisted Permeation of Lidocaine Carboxymethylcellulose with Gelatine Co-polymer Hydrogel

Purpose

Lidocaine hydrochloride (LidH) was formulated in sodium carboxymethyl cellulose/ gelatine (NaCMC/GEL) hydrogel and a ‘poke and patch’ microneedle delivery method was used to enhance permeation flux of LidH.

Methods

The microparticles were formed by electrostatic interactions between NaCMC and GEL macromolecules within a water/oil emulsion in paraffin oil and the covalent crosslinking was by glutaraldehyde. The GEL to NaCMC mass ratio was varied between 1.6 and 2.7. The LidH encapsulation yield was 1.2 to 7% w/w. LidH NaCMC/GEL was assessed for encapsulation efficiency, zeta potential, mean particle size and morphology. Subsequent in vitro skin permeation studies were performed via passive diffusion and microneedle assisted permeation of LidH NaCMC/GEL to determine the maximum permeation rate through full thickness skin.

Results

LidH 2.4% w/w NaCMC/GEL 1:1.6 and 1:2.3 respectively, possessed optimum zeta potential. LidH 2.4% w/w NaCMC/GEL 1:2.3 and 1:2.7 demonstrate higher pseudoplastic behaviour. Encapsulation efficiency (14.9–17.2%) was similar for LidH 2.4% w/w NaCMC/GEL 1:1.6–1:2.3. Microneedle assisted permeation flux was optimum for LidH 2.4% w/w NaCMC/GEL 1:2.3 at 6.1 μg/ml/h.

Conclusion

LidH 2.4% w/w LidH NaCMC/GEL 1:2.3 crossed the minimum therapeutic drug threshold with microneedle skin permeation in less than 70 min.     

Hydnocarpus: An ethnopharmacological,phytochemical and pharmacological review

Ethnopharmacological relevance

The genus Hydnocarpus (Flacourtiaceae) includes forty species that are spread across the globe. In the Indian System of Medicine, Hydnocarpus pentandrus (Buch.-Ham.) Oken. is primarily used for treating leprosy and other skin disorders. It is known as “Chaulmoogra” and is also used to treat other indications including constipation, inflammation, blood disorders, and worm infestations. Various species of Hydnocarpus are also used in traditional medicine in China, Thailand, Malaysia, and Myanmar for several skin disorders. To assess the therapeutic potential of species from the Hydnocarpus genus and to determine future avenues for research.

Methods

All relevant scientific literature published up to the end of December 2013 was retrieved via a library and electronic search (SciFinder, PubMed, ScienceDirect, and Google Scholar). Manual searches of traditional books like to ancient classics, including Vaidya Yoga Ratnavali, Siddha Materia Medica, and contemporary references including The Ayurvedic Pharmacopoeia of India and The Ayurveda Formulary, were also performed.

Results

Seed oil from species of the Hydnocarpus genus is used for medicinal purposes, predominantly for various skin disorders. This oil is reported to contain a characteristic class of compounds known as cyclopentenyl fatty acids. Furthermore, seeds of this genus are reported to contain triglycerides of fatty acids, sterols, flavonoids, and flavonolignans. Hydnocarpin, a flavonolignan, is reported to potentiate antimicrobial and anticancer activity. The extracts and compounds isolated from this plant show a wide spectrum of pharmacological properties, including antibacterial, antileprotic, antitubercular, antipsoriatic, antirheumatic, hypolipidemic, antidiabetic, anticancer, anti-inflammatory, and antioxidant activities. The antileprotic activity is postulated to be due to the cyclopentenyl fatty acids present in the seed oil.

Conclusion

Flavonolignans have an interesting chemical motif, and hydnocarpin and its congeners should be investigated for their activities and the mechanism underlying these activities. Multi-drug-resistant microbes are on the increase, and the possible inhibitory effect of these compounds when used with current antimicrobials should also be evaluated. Furthermore, unique cyclopentenyl fatty acids should also be investigated to understand the exact mechanism of action underlying antileprotic activity. Additional in depth phytochemical investigations of seed oil and extracts are required to tap the true potential of species from the Hydnocarpus genus.     

Inhaled Microparticles Containing Clofazimine Are Efficacious in Treatment of Experimental Tuberculosis in Mice

Inhalable clofazimine-containing dry powder microparticles (CFM-DPI) and native clofazimine (CFM) were evaluated for activity against Mycobacterium tuberculosis in human monocyte-derived macrophage cultures and in mice infected with a low-dose aerosol. Both formulations resulted in 99% killing at 2.5 μg/ml in vitro. In mice, 480 μg and 720 μg CFM-DPI inhaled twice per week over 4 weeks reduced numbers of CFU in the lung by as much as log₁₀ 2.6; 500 μg oral CFM achieved a log₁₀ 0.7 reduction.